Patent Docs

Patent Profile: StemCells Announces Issuance of Human Neural Stem Cell Patent

    By Donald Zuhn --

Yesterday, StemCells, Inc. announced that the U.S. Patent and Trademark Office has issued U.S. Patent No. 7,361,505, which is directed to multipotent neural stem cell compositions.  While the '505 patent is assigned to Neurospheres Holdings Ltd., StemCells notes that it has exclusively licensed the patent.  As we reported earlier this week, StemCells is currently involved in a litigation with Neuralstem regarding four of StemCells' other multipotent neural stem cell patents (see "StemCells' Patents Survive Reexam -- StemCells and Neuralstem Differ on Extent of Changes").

According to StemCells' statement, the '505 patent contains "broad claims covering human neural stem cells derived from any tissue source, including embryonic, fetal, juvenile, or adult tissue."  StemCells President and CEO Martin McGlynn believes the issuance of the '505 patent "rounds out and strengthens" the Palo Alto-based biotech company's neural stem cell portfolio, which he called "unparalleled in its breadth, depth and completeness."  Mr. McGlynn added that StemCells was "confident that any third party wishing to commercialize neural stem cells as potential therapeutics or to use them as drug screening tools will have to seek a license from us irrespective of how they derive the cells."

The '505 patent issued from U.S. Application No. 08/480,172, filed June 7, 1995, which claims the benefit of series of continuation-in-part applications going back to July 8, 1991.  Independent claims 1, 9, 13, 14, 18, and 24-26 of the '505 patent recites:

1.  A pure in vitro cell culture composition derived from the embryonic or fetal mammalian CNS consisting of neurospheres and culture medium, wherein said neurospheres consist of undifferentiated neural cells that are: nestin+ and; are glial fibrillary acidic protein (GFAP)-; neurofilament (NF)-; and myelin basic protein (MBP)-; and not nestin-.

9.  A purified population of multipotent neural stem cells derived from juvenile or adult mammalian CNS tissue that includes tissue from the subependymal region lining the ventricles in the forebrain, conus medullaris, thoracic spinal cord, brain stem, or hypothalamus.

13.  A pure in vitro cell culture composition derived from mammalian CNS consisting of neurospheres and culture medium, wherein said neurospheres consist of undifferentiated neural cells that are: nestin+ and; are glial fibrillary acidic protein (GFAP)-; neurofilament (NF)-; and myelin basic protein (MBP)-; and not nestin-.

14.  A pure in vitro cell culture composition derived from juvenile or adult mammalian CNS tissue consisting of neurospheres and culture medium, wherein said neurospheres consist of undifferentiated neural cells that are: nestin+ and; are glial fibrillary acidic protein (GFAP)-; neurofilament (NF)-; and myelin basic protein (MBP)-; and not nestin-.

18.  A pure in vitro cell culture composition derived from mammalian CNS tissue consisting of neurospheres and culture medium, wherein said neurospheres consist of undifferentiated neural cells that stain positive for nestin and said neurospheres lack differentiated neural cells that do not stain positive for nestin but that stain positive for the differentiated neural cell markers neurofilament, glial fibrillary acidic protein and myelin basic protein.

24.  A purified population of multipotent neural stem cells isolated from the embryonic or fetal mammalian CNS, wherein the neural stem cells are human cells.

25.  A pure in vitro cell culture composition consisting of neurospheres and culture medium, wherein said neurospheres consist of undifferentiated neural cells that are: nestin+ and; are glial fibrillary acidic protein (GFAP)-; neurofilament (NF)-; and myelin basic protein (MBP)-; and not nestin-.

26.  A pure in vitro cell culture composition consisting of neurospheres and culture medium, wherein said neurospheres consist of undifferentiated neural cells that stain positive for nestin and said neurospheres lack differentiated neural cells that do not stain positive for nestin but that stain positive for the differentiated neural cell markers neurofilament, glial fibrillary acidic protein and myelin basic protein.

Patent Profile: Redpoint Bio Announces Issuance of Patent for Identifying Taste Signaling Modulators

    By Donald Zuhn --

Redpoint Bio Corp. announced earlier this month that the U.S. Patent and Trademark Office has issued U.S. Patent No. 7,341,842, which is directed to methods of methods for identifying modulators of the TRP8-mediated taste response.  Such modulators can be used as flavor enhancers in foods, beverages, or pharmaceuticals to either inhibit or promote the perception of bitterness or sweetness.  While the '842 patent is assigned to the Mount Sinai School of Medicine, Redpoint Bio notes that it has exclusively licensed the patent.

According to Redpoint Bio's statement, the '842 patent covers assay technology that can be used to identify modulators of the TRPM5 (formerly TRP8) ion channel).  The TRPM5 ion channel, which is highly expressed in taste receptor cells, is associated with the perception of bitter, sweet, and savory (umami) tastes.  Redpoint Bio CEO Dr. Raymond Salemme stated that the '842 patent would significantly strengthen the Ewing, N.J-based biotech company's intellectual property position with respect to taste modulators of TRPM5.  Redpoint Bio's pharmaceutical program uses a biochemical approach aimed at suppressing the bitterness of medicines, which has the potential to expand the range of formulation options and increase patient compliance.

Figure 14 of the '842 patent shows potential signal transduction pathways in the taste receptor cells of taste buds that involve TRPM5 (TRP8).  The '842 patent explains that responses to bitter compounds are initiated by binding to one or more gustducin-coupled receptors of the T2R/TBR family, which results in the release of that molecule's beta-gamma moiety, which in turn stimulates PLC-beta2, resulting in the production of inositol triphosphate (IP) and diacylglycerol (DAG).  IP binds to its receptors and causes the release of Ca++ from intracellular stores, triggering activation of TRP8 channels, which ultimately leads to the influx of Ca++ through TRP8 channels.  DAG may act directly on TRP8 to lead to Ca++ influx.

The '842 patent issued from U.S. Application No. 11/405,097, filed April 17, 2006, which is a divisional of U.S. Application No. 09/834,792, filed April 13, 2001, which claims the benefit of U.S. Provisional Application No. 60/197,491, filed April 17, 2000.  Representative claim 1 of the '842 patent recites:

1.  A method for identifying a compound that modulates TRP8 activity, said method comprising:
    (i) contacting a cell expressing the TRP8 channel protein of SEQ ID NO: 4 with a test compound and a compound or molecular complex that results in TRP8 activation, and measuring the level ofTRP8 activation;
    (ii) in a separate experiment, contacting a cell expressing the TRP8 channel protein of SEQ ID NO: 4 with a compound or molecular complex that results in TRP8 activation and measuring the level of TRP8 activation, where the conditions are essentially the same as in part (i); and
    (iii) comparing the level of TRP8 activation measured in part (i) with the level of TRP8 activation measured in part (ii),
    wherein said measuring the level of TRP8 activation comprises measuring the membrane potential of the cell, and
    wherein a decrease in the level of TRP8 activation in the presence of the test compound indicates that the test compound is a TRP8 inhibitor, and an increase in the level of TRP8 activation in the presence of the test compound indicates that the test compound is a TRP8 activator.

Patent Profile: OPKO Health Announces Issuance of VEGF siRNA Patent

    By Donald Zuhn --

OPKO Health, Inc. announced yesterday that the U.S. Patent and Trademark Office has issued U.S. Patent No. 7,345,027, which is directed to methods of inhibiting the expression of human vascular endothelial growth factor (VEGF), degrading VEGF mRNA, inhibiting angiogenesis, or treating an angiogenic disease using a specific short interfering ribonucleic acid (siRNA) molecule.  While the '027 patent is assigned to the Trustees of the University of Pennsylvania, OPKO states that it has exclusively licensed the patent on a worldwide basis.

According to OPKO's statement, the '027 patent covers the Miami-based healthcare company's siRNA drug candidate, bevasiranib, which is currently in a Phase III trial for the treatment of wet age-related macular degeneration (AMD).  In addition, the '027 patent covers the use of the recited siRNA molecule for treating VEGF-related angiogenic disorders such as diabetic retinopathy and cancer.  OPKO Executive Vice President Samuel Reich stated that the issuance of the '027 patent "marks another important step in establishing OPKO's leadership position in the promising field of siRNA-based therapeutics," observing that "Bevasiranib was the first siRNA to enter human trials, the first siRNA to demonstrate clinically relevant activity in patients, the first siRNA to enter a Phase III pivotal trial and now, one of the first siRNAs to receive a U.S. patent covering its broad therapeutic use."  OPKO's release also noted that the multi-national Phase III COBALT (Combining Bevasiranib And Lucentis Therapy) clinical trial of bevasiranib for the treatment of wet AMD is currently enrolling patients at multiple clinical sites, and that more information about the COBALT trial could be obtained here.

The '027 patent issued from U.S. Application No. 11/422,932, filed June 8, 2006, which is a divisional of U.S. Application No. 10/294,228, filed November 14, 2002, which issued as U.S. Patent No. 7,148,342, which claims the benefit of U.S. Provisional Application No. 60/398,417, filed July 24, 2002.  Representative claims 1, 24, 29, and 40 of the '027 patent recite:

1.  A method of inhibiting expression of human vascular endothelial growth factor (VEGF) comprising:
    administering to a subject an effective amount of a short interfering ribonucleic acid (siRNA) comprising a sense RNA strand and an antisense RNA strand, wherein the sense and the antisense RNA strands form an RNA duplex, and wherein the sense RNA strand comprises a nucleotide sequence identical to a target sequence of about 19 to about 25 contiguous nucleotides in human vascular endothelial growth factor (VEGF) mRNA and wherein the sense RNA strand comprises SEQ ID NO:77, and the antisense strand comprises SEQ ID NO:78.

24.  A method of inhibiting angiogenesis in a subject comprising:
    administering to the subject an effective amount of a short interfering ribonucleic acid (siRNA) a sense RNA strand and an antisense RNA strand, wherein the sense and the antisense RNA strands form an RNA duplex, and wherein the sense RNA strand comprises a nucleotide sequence identical to a target sequence of about 19 to about 25 contiguous nucleotides in human vascular endothelial growth factor (VEGF) mRNA and wherein the sense RNA strand comprises SEQ ID NO: 77 and the antisense strand comprises SEQ ID NO: 78.

29.  A method of treating an angiogenic disease in a subject comprising:
    administering to a subject an effective amount of a short interfering ribonucleic acid (siRNA) comprising a sense RNA strand and an antisense RNA strand, wherein the sense and the antisense RNA strands form an RNA duplex, and wherein the sense RNA strand comprises a nucleotide sequence identical to a target sequence of about 19 to about 25 contiguous nucleotides in human vascular endothelial growth factor (VEGF) mRNA, and wherein the sense RNA strand comprises SEQ ID NO: 77 and the antisense strand comprises SEQ ID NO: 78, such that angiogenesis associated with the angiogenic disease is inhibited.

40.  A method of degrading human vascular endothelial growth factor (VEGF) mRNA comprising:
    administering to a subject an effective amount of a short interfering ribonucleic acid (siRNA) comprising a sense RNA strand and an antisense RNA strand, wherein the sense and the antisense RNA strands form an RNA duplex, and wherein the sense RNA strand comprises a nucleotide sequence identical to a target sequence of about 19 to about 25 contiguous nucleotides in human vascular endothelial growth factor (VEGF) mRNA and wherein the sense RNA strand comprises SEQ ID NO: 77, and the antisense strand comprises SEQ ID NO: 78.

Patent Profile: Commonwealth Biotechnologies Announces Issuance of Patent Related to Real Time PCR Detection of Herpes Virus

    By Donald Zuhn --

Commonwealth Biotechnologies, Inc. announced today that it has been granted U.S. Patent No. 7,338,761.  According to Commonwealth's press release, while the '761 patent is assigned to Vigen Laboratories, the patent is exclusively licensed to CBI Services, a Commonwealth business unit, which developed the claimed invention under contract to Vigen Laboratories.  Commonwealth's release also notes that the two named co-inventors of the '761 patent are CBI President Robert Harris and CBI Executive Vice President Thomas Reynolds.  Now that the '761 patent has issued, Commonwealth and Vigen are looking to out-license the patented technology to a clinical laboratory
service provider who can commercialize the assay on a large scale, with the two companies to share equally in licensing revenue.

The '761 patent is directed to real time PCR-based assays and polynucleotide sets for detecting human herpes viruses.  According to Commonwealth's statement, the platform described in the '761 patent provides a "rapid and specific assay of each of the various [human herpes viruses] down to as few as 10 copies of viral DNA in patient samples," and "has been successfully applied to peripheral blood serum, sputum, cerebrospinal fluid, and various laboratory preparations."

There are eight known human herpes viruses (HHVs), which can be divided into three classes:  the alpha herpes viruses, which include HSV 1 (simplex virus), HSV 2 (simplex virus), and HHV 3 (varicellovirus); the beta herpes viruses, which include HHV 5 (cytomegalovirus), HHV 6, and HHV 7 (Roseolovirus); and the gamma herpes viruses, which include HHV 4 (Epstein Barr virus) and HHV 8 (Rhadinovirus).  The herpes viruses are associated with a number of conditions, including:

• HHV 1 and 2 are the causative agents of genital herpes.
• HHV 4 is associated with infectious mononucleosis (glandular fever), chronic-fatigue syndrome, oncogenesis (particularly in relation to Burkitt’s lymphoma nasopharyngeocarcinoma), immuno-suppression, and Hodgkin’s disease.
• HHV 5 is associated with chronic-fatigue syndrome, and is known to cause lung infections in immune-suppressed persons.
• HHV 6 is associated with roseola and infantum infection in children and with immuno-compromised patients, and may perhaps be involved with multiple sclerosis and chronic fatigue syndrome.
• HHV 8 appears to be associated with Karposi’s Sarcoma.

The '761 patent issued from U.S. Application No. 10/399,872, which is a national stage application of International Application No. PCT/US01/31892, filed October 12, 2001, which claims the benefit of U.S. Provisional Application No. 60/242,903, filed October 24, 2000.  Representative claims 1, 16, and 17 of the '761 patent recite:

1.  A set of polynucleotide molecules wherein the set comprises the polynucleotide molecules consisting of SEQ ID NOS: 33, 34, and 35 and optionally a fourth polynucleotide molecule comprising SEQ ID NO: 57.

16.  A method for detecting infection by HHV6 in a sample from an individual suspected of being infected with HHV6, comprising:
    (a) amplifying, in the course of a single amplification reaction, a target segment of an HHV6 glycoprotein B gene comprising SEQ ID NO: 57 using primers and a probe consisting of SEQ ID NOS: 33, 34, and 35 and
    (b) interpolating the number of HHV6 viral nucleic acid copies in the sample by comparing the number of amplification cycles required for detection of the target segment to the number of amplification cycles required to detect a known quantity of the target segment.

17.  A method for detecting infection by either HHV6a or HHV6b in a sample from an individual suspected of being infected with either HHV6a or HHV6b, comprising:
    (a) amplifying, in the course of a single amplification reaction, a target segment of an HHV6 glycoprotein B gene comprising SEQ ID NO: 57, using primers and a probe consisting of SEQ ID NOS: 33, 34, and 35; and
    (b) interpolating the number of either HHV6a or HHV6b viral nucleic acid copies in the sample by comparing the number of amplification cycles required for detection of the target segment to the number of amplification cycles required to detect a known quantity of the target segment.

OREXIGEN Therapeutics Secures Allowance for Application Covering Zonisamide

    By Baltazar Gomez --

Last Thursday, OREXIGEN Therapeutics, Inc. announced that the U.S. Patent and Trademark Office mailed a Notice of Allowance for a patent application directed to the treatment of obesity using zonisamide, either alone or in combination with other drugs.  According to OREXIGEN, the allowed application will complement U.S. Patent No. 7,109,198.  Both the recently allowed application (believed to be U.S. Application No. 10/830,071) and the '198 patent, the latter of which OREXIGEN has exclusively licensed from Duke University, will expire in 2023.

OREXIGEN President and CEO, Dr. Gary Tollefson, stated that "[t]his notice from the USPTO is an important milestone toward issuance of the patent and would give us an additional layer of protection for our use of zonisamide in treating obesity."  Dr. Tollefson believes that the allowed application will discourage competitors from copying OREXIGEN's approach for treating obesity with zonisamide-based compounds.

Zonisamide is one of the active constituents of EMPATIC, a novel formulation of zonisamide and bupropion.  Bupropion is a dopamine and norepinephrine re-uptake inhibitor while zonisamide is an approved anticonvulsant medication.  The rationale behind EMPATIC is that the combination of zonisamide and bupropion affects two groups of hypothalamic neurons, the POMC and NPY/AgRP neurons, to reduce the feeling of hunger.  The POMC neurons release the hormone alpha-MSH while the NPY/AgRP neurons release AgRP.  Both alpha-MSH and AgRP competitively bind to the melanocortin MC4 receptors; alpha-MSH binding increases energy expenditure and reduces hunger, while AgRP binding reduces energy expenditure and increases hunger.  In addition, monoamines, such as dopamine, norepinephrine, and serotonin, stimulate the neurons increasing alpha-MSH secretion and reducing AgRP secretion.  The novel combination of zonisamide and bupropion exploits the opposing effects of alpha-MSH and AgRP on MC4.  Zonisamide increases monoamine secretion which increases alpha-MSH secretion and reduces AgRP secretion, while bupropion increases alpha-MSH secretion by stimulating POMC.  The net effect is that alpha-MSH is overproduced and AgRP is reduced, leading to increased energy expenditure and reduced hunger.

Results of clinical studies support OREXIGEN's rationale for weight loss.  Studies with EMPATIC have shown that meaningful weight loss is sustainable over long periods.  Patients with body mass indices between 30 and 40 lost in excess of 9% of their baseline body weight by week 24.  In addition, weight loss continued for another 24 weeks with patients averaging a weight loss of 12% from baseline.  The weight loss was dose dependent with the highest dose achieving the greatest weight loss.

OREXIGEN is also pursuing another drug combination, CONTRAVE, which in patient studies has shown weight loss without a plateau after 36 weeks of treatment.  CONTRAVE is a combination of bupropion and naltrexone designed to block the natural inhibition of alpha-MSH secretion by ß-endorphin.

Obesity has become a major health problem in the Unites States and around the World.  The World Health Organization estimates that there are more than 1 billion overweight adults worldwide, and that at least 300 million of these individuals are clinically obese.  In the United States, data from two National Health and Nutrition Examination Surveys show that among adults aged 20-74 years, the prevalence of obesity increased from 15.0% (in the 1976-1980 survey) to 32.9% (in the 2003-2004 survey).  But obesity also increases the risk of many serious diseases, such as hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, respiratory problems, and even cancer.  So therapies such as EMPATIC and CONTRAVE represent important advances in the fight against obesity.

Among the allowed claims of the '071 application are independent claims 18, 35, 44, and 53:

18.  A method of reducing the weight of an overweight subject, said method comprising:  identifying an overweight subject and administering to said overweight subject a pharmaceutical composition comprising zonisamide, or a pharmaceutically acceptable salt thereof, in an amount effective to reduce the weight of said subject.

35.  A method of reducing weight in an overweight subject, said method comprising:  identifying an overweight subject and administering to said overweight subject a pharmaceutical composition comprising zonisamide, or a pharmaceutically acceptable salt thereof, in an amount effective to induce weight loss in said subject, wherein the weight loss
is ≥ 5%, or wherein said weight loss continues during the period of administration of said composition comprising zonisamide or a pharmaceutically acceptable salt thereof.

44.  A method of treating obesity by reducing the weight of an obese subject, said method comprising:  identifying an obese subject and administering to said obese subject an effective amount of a pharmaceutical composition comprising zonisamide, or a pharmaceutically acceptable salt thereof.

53.  A method of treating obesity by reducing the weight of an obese subject, said method comprising:  identifying an obese subject and orally administering to said obese subject a capsule comprising a pharmaceutical composition comprising zonisamide or a pharmaceutically acceptable salt thereof, wherein said subject receives a daily dose of 100 to 600 mg of zonisamide.

(Figure 1 of Wisse et al., "The skinny on  neurotrophins," Nature Neuroscience 6:655-56 (2003))

Patent Profile: Geron Receives Patent for Producing Pancreatic Islets from Embryonic Stem Cells

    By Kwame Mensah --

Geron Corporation recently announced that it had been granted U.S. Patent No. 7,326,572, entitled "Endoderm cells from human embryonic stem cells."  The '572 patent covers a method for producing endoderm cells from human embryonic stem cells (hESCs).  The production of endoderm cells is a critical step in generating pancreatic islet cells from hESCs.  Geron is developing ways to use this method in the treatment of diabetes.

Geron's senior vice president of business development and chief patent counsel, Dr. David J. Earp, believes that the '572 patent broadens the coverage for Geron's islet cell production protocol beyond the scope of U.S. Patent No. 7,033,831, which was issued to Geron in 2006.  Earp states that "[a]dded to our already robust portfolio of IP covering the scalable production of pluripotent stem cells, these patents reinforce our proprietary position for diabetes cell therapy."

Geron's president and chief executive officer, Dr. Thomas B. Okarma, commented on the utility of the method covered by the patent stating that it "has been validated in a number of studies published in leading journals by scientists from both Geron and other organizations."  Okarma also states that transplanted pancreatic islet cells of the method prolong the survival of severely diabetic animals as well as produce detectable human insulin in their bloodstream.  Geron is continuing to develop plans "aimed at producing a cell therapy capable of restoring normal glucose regulation in patients suffering from diabetes."

Geron's portfolio of owned and in-licensed patents includes over 30 patents issued in the U.S., more than 65 issued in other countries, and over 130 applications pending worldwide that relate to pluripotent stem cells.  Geron also holds the exclusive right to develop and commercialize hESC-derived pancreatic islet cells, cardiomyocytes, and neural cells for therapeutic applications under the fundamental hESC patents assigned to the Wisconsin Alumni Research Foundation (WARF).

The '572 patent is a divisional of U.S. Patent Application No. 10/313,739, filed Dec. 6, 2002, now U.S. Patent No. 7,033,831, which claims priority to U.S. Provisional Application No. 60/338,885, filed Dec. 7, 2001.  Representative claims 1 and 3 of the '572 patent recite:

1.  A method for generating endoderm cells from human embryonic stem (hES) cells or human embryonic germ (hEG) cells, comprising culturing the hES cells or hEG cells in a medium comprising a sufficient amount of Activin A to cause differentiation of said cells into endoderm, thereby generating endoderm cells, wherein the endoderm cells express the markers Sox 17, HNF313 and HNF4a.

3.  The method of claim 1, wherein the cells are human embryonic stem cells.

For additional information regarding this or other related topics, please see:

• "stART Licensing Announces Issuance of Patents for Cloning Ungulates," January 3, 2008
• "It's Time to Stop the Hypocrisy over Stem Cell Patents - Part III," July 4, 2007
• "It's Time to Stop the Hypocrisy over Stem Cell Patents - Part II," April 26, 2007

Patent Profile: Senomyx Announces Issuance of "Sweet and Savory" Patents

    By Donald Zuhn --

Senomyx, Inc. announced last week that it has been granted five U.S. patents directed to human umami and sweet taste receptors.  The patents are U.S. Patent Nos. 7,294,474; 7,297,543; 7,297,772; 7,301,009; and 7,309,577.  With the addition of the five new patents, the San Diego-based company, which uses proprietary taste receptor technologies to discover and develop novel flavor ingredients for the food, beverage, and ingredient supply industries, now has sixteen U.S. patents in its portfolio.

According Dr. Mark Zoller (at left), Senomyx Chief Scientific Officer and Executive Vice President of Discovery and Development, the five patents "add to Senomyx's already extensive taste receptor patent franchise and expand upon [the company's] earlier patents relating to the human sweet and umami (savory) taste receptors" (the five basic tastes include sweetness, sourness, bitterness, saltiness, and umami -- or savoriness).  Dr. Zoller explained that the new patents would strengthen Senomyx's position regarding the use of the claimed taste receptors in screening assays designed to identify new flavor ingredients that induce or modulate sweet and savory tastes.  For example, Senomyx has used taste receptor assays similar to those claimed in the new patents to discover S2383, an enhancer of the artificial sweetener sucralose, and S5742, an enhancer of sucrose (table sugar).  Senomyx is currently involved in product discovery and development collaborations with Ajinomoto Co., Inc., Cadbury Schweppes, Campbell Soup Company, The Coca-Cola Company, Firmenich SA, Nestlé SA, and Solae, LLC.

Representative independent claims 1 and 40 of the '474 patent, which issued from U.S. Application No. 10/725,475, recites:

1.  A method for identifying a compound that potentially modulates a T1R2/T1R3 receptor comprising:
    (i) screening one or more compounds in a functional assay that detects compounds which modulate (enhance or inhibit) the activity of the T1R2/T1R3 receptor by another compound; and
    (ii) identifying compounds that potentially modulate the T1R2/T1R3 receptor-based on their modulation (enhancement or inhibition) of the activity of the T1R2/T1R3 receptor by another compound, wherein said T1R2 is a T1R2 polypeptide and is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 10, (ii) encoded by a nucleic acid sequence comprising a nucleic acid that hybridizes to SEQ. ID. NO: 10 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, and 1% SDS and washing at 65o C. in a solution comprising 0.2xSSC and 0.1% SDS, or (iii) a T1R2 polypeptide possessing at least 90% sequence identity to the T1R2 polypeptide of SEQ. ID. NO: 6;
    wherein said T1R3 is a T1R3 polypeptide and is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 9; (ii) encoded by a nucleic acid sequence that hybridizes to SEQ. ID. NO: 9 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, 10% SDS; and washing at 65o C. in a solution comprising 0.2xSCC and 0.1% SDS, or (iii) a T1R3 polypeptide possessing at least 90% sequence identity to the T1R3 polypeptide of SEQ. ID. NO: 7;
    and wherein said T1R2/T1R3 receptor specifically binds to a ligand that specifically binds to an endogenous (wild-type) human T1R2/T1R3 receptor comprised of at least one endogenous T1R2 polypeptide and at least one endogenous T1R3 polypeptide.

Representative independent claims 1 and 40 of the '543 patent, which issued from U.S. Application No. 10/725,103, recite:

1.  An isolated recombinant cell that expresses a heteromeric taste receptor, wherein said receptor is comprised of at least one T1R2 polypeptide and at least one T1R3 polypeptide, wherein said T1R2 polypeptide is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 10, (ii) encoded by a nucleic acid sequence comprising a nucleic acid that hybridizes to SEQ. ID. NO: 10 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, and 1% SDS and washing at 65o C. in a solution comprising 0.2xSSC and 0.1% SDS, or (iii) a T1R2 polypeptide possessing at least 90% sequence identity to the T1R2 polypeptide of SEQ. ID. NO: 6;
    wherein said T1R3 polypeptide is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 9; (ii) encoded by a nucleic acid sequence that hybridizes to SEQ. ID. NO: 9 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formaniide [sic], 5xSSC, 10% SDS; and washing at 65o C. in a solution comprising 0.2xSCC and 0.1% SDS, or (iii) a T1R3 polypeptide possessing at least 90% sequence identity to the T1R3 polypeptide of SEQ. ID. NO: 7;
    and wherein said isolated cell expresses a heteromeric taste receptor that specifically binds to a ligand that specifically binds to an endogenous (wild-type) human heteromeric T1R2/T1R3 receptor comprised of at least one endogenous T1R2 polypeptide and at least one endogenous T1R3 polypeptide.

40.  An isolated eukaryotic recombinant cell that expresses a heteromeric taste receptor, wherein said receptor is comprised of at least one T1R2 polypeptide and at least one T1R3 polypeptide, wherein said T1R2 polypeptide is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 10, (ii) encoded by a nucleic acid sequence comprising a nucleic acid that hybridizes to SEQ. ID. NO: 10 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, and 1% SDS and washing at 65o C. in a solution comprising 0.2xSSC and 0.1% SDS, or (iii) a T1R2 polypeptide possessing at least 90% sequence identity to the T1R2 polypeptide of SEQ. ID. NO: 6;
    wherein said T1R3 polypeptide is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 9; (ii) encoded by a nucleic acid sequence that hybridizes to SEQ. ID. NO: 9 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, 10% SDS; and washing at 65o C. in a solution comprising 0.2xSCC and 0.1% SDS, or (iii) a T1R3 polypeptide possessing at least 90% sequence identity to the T1R3 polypeptide of SEQ. ID. NO: 7;
    and wherein said isolated cell expresses a heteromeric taste receptor that specifically binds to a ligand that specifically binds to an endogenous (wild-type) human heteromeric T1R2/T1R3 receptor comprised of at least one endogenous T1R2 polypeptide and at least one endogenous T1R3 polypeptide.

Representative independent claim 1 of the '772 patent, which issued from U.S. Application No. 10/725,037, recites:

1.  An isolated heteromeric receptor comprising at least one T1R2 polypeptide and at least one T1R3 polypeptide, wherein said T1R2 polypeptide is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 10, (ii) encoded by a nucleic acid sequence comprising a nucleic acid that hybridizes to SEQ. ID. NO: 10 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, and 1% SDS and washing at 65o C. in a solution comprising 0.2xSSC and 0.1% SDS, or (iii) a T1R2 polypeptide possessing at least 90% sequence identity to the T1R2 polypeptide of SEQ. ID. NO: 6;
    wherein said T1R3 polypeptide is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 9; (ii) encoded by a nucleic acid sequence that hybridizes to SEQ. ID. NO: 9 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, 10% SDS; and washing at 65o C. in a solution comprising 0.2xSCC and 0.1% SDS, or (iii) a T1R3 polypeptide possessing at least 90% sequence identity to the T1R3 polypeptide of SEQ. ID. NO: 7;
    and wherein said heteromeric receptor comprised of at least on [sic] T1R2 polypeptide and at least one T1R3 polypeptide specifically binds to a ligand that specifically binds to an endoenous (wild-type) human heteromeric T1R2/T1R3 receptor.

Representative independent claim 1 of the '009 patent, which issued from U.S. Application No. 10/725,080, recites:

1. An isolated heteromeric receptor comprising at least one T1R1 polypeptide and at least one T1R3 polypeptide, wherein said T1R1 polypeptide is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 8, (ii) encoded by a nucleic acid sequence comprising a nucleic acid that hybridizes to SEQ. ID. NO: 8 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, and 1% SDS and washing at 65o C. in a solution comprising 0.2xSSC and 0.1% SDS, or (iii) a T1R1 polypeptide possessing at least 95% sequence identity to the T1R1 polypeptide of SEQ. ID. NO: 5;
    wherein said T1R3 polypeptide is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 9; (ii) encoded by a nucleic acid sequence that hybridizes to SEQ. ID. NO: 9 or under stringent hybridization conditions which are conducting the hybridization reaction at 42 [sic] C. in a solution comprising 50% formamide, 5xSSC, 10% SDS; and washing at 65o C. in a solution comprising 0.2xSCC and 0.1% SDS, or (iii) a T1R3 polypeptide possessing at least 95% sequence identity to the T1R3 polypeptide of SEQ. ID. NO: 7;
    and wherein said heteromeric receptor comprised of at least one T1R1 polypeptide and at least one T1R3 polypeptide specifically binds to a ligand that specifically binds to an endogenous (wild-type) human heteromeric T1R1/T1R3 receptor.

Representative independent claim 1 of the '577 patent, which issued from U.S. Application No. 10/725,418, recites:

1.  A method for identifying a compound that potentially modulates a T1R1/T1R3 receptor comprising:
    (i) screening one or more compounds in a binding assay which identifies compounds that specifically bind to a T1R1/T1R3 receptor or which specifically modulate (enhance or inhibit) the specific binding of another compound to a T1R1/T1R3 receptor; and
(ii) identifying compounds that potentially modulate T1R1/T1R3 based on their (a) specific binding to a T1R1/T1R3 receptor or (b) modulation of the specific binding of another compound to a T1R1/T1R3 receptor, wherein said T1R1 is a T1R1 polypeptide and is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 8, (ii) encoded by a nucleic acid sequence comprising a nucleic acid that hybridizes to SEQ. ID. NO: 8 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, and 1% SDS and washing at 65o C. in a solution comprising 0.2xSSC and 0.1% SDS, or (iii) a T1R1 polypeptide possessing at least 95% sequence identity to the T1R1 polypeptide of SEQ. ID. NO: 5;
    wherein said T1R3 is a T1R3 polypeptide and is (i) encoded by a nucleic acid sequence comprising SEQ. ID. NO: 9; (ii) encoded by a nucleic acid sequence that hybridizes to SEQ. ID. NO: 9 under stringent hybridization conditions which are conducting the hybridization reaction at 42o C. in a solution comprising 50% formamide, 5xSSC, 10% SDS; and washing at 65o C. in a solution comprising 0.2xSCC and 0.1% SDS, or (iii) a T1R3 polypeptide possessing at least 95% sequence identity to the T1R3 polypeptide of SEQ. ID. NO: 7;
    and wherein said T1R1/T1R3 receptor specifically binds to a ligand that specifically binds to an endogenous (wild-type) human T1R1/T1R3 receptor comprised of at least one endogenous T1R1 polypeptide and at least one endogenous T1R3 polypeptide.

Patent Profile: PuriCore Announces Issuance of Patent for Wound and Ulcer Treatment

    By Kwame Mensah --

PuriCore recently announced that it had been granted U.S. Patent No. 7,276,255, entitled "Wound and Ulcer Treatment with Super-Oxidized Water."  The '255 patent covers methods of treating an open wound with hypochlorous acid solutions at neutral or near-neutral pH.  The method includes two processes:  reducing wound bioburden and promoting tissue repair.  Research data submitted with the application show that the method of the invention creates a wound-healing environment by decreasing the bioburden of harmful microorganisms within the wound and by promoting skin cell proliferation and re-growth.

The '255 patent is the first U.S. patent specifically related to wound therapy to be issued to PuriCore, whose research focuses on the control of infectious pathogens.  Commenting on the issuance of the '255 patent, PuriCore CEO Greg Bosch stated that "the granting of this patent complements our broad intellectual property portfolio focused on antimicrobial solutions and devices for producing these solutions."  In addition to the '255 patent, PuriCore's patent portfolio comprises U.S. Patent No. 6,632,347 and recently-issued U.S. Patent No. 7,303,660.

The '255 patent issued from U.S. Application Number 10/830,878, filed April 23, 2004.  Representative independent claims 1 and 18 of the '255 patent recite:

1.  A method for treating an open wound in a human or animal body comprising administering to the open wound an output solution comprising hypochlorous acid, said output solution: having a pH of 4 to 7, a redox potential of >950 mV, and being obtained by electrochemical treatment of a saline solution; and wherein the output solution is administered in an amount effective to act as a biocide and permit cell proliferation for wound healing.

18.  A method for treating an open wound in a mammal comprising administering to the open wound an output solution obtained by electrochemical treatment of a saline solution, the output solution comprising hypochlorous acid, having an available free chlorine concentration of about 144 mg/l to 400 mg/l, and having a pH of 4 to 7, wherein the output solution is administered in an amount effective to act as a biocide and permit cell proliferation for wound healing.

Patent Profile: Proteologics Announces Issuance of POSH siRNA Patent

    By Donald Zuhn ---

Proteologics, Inc. announced today that it has been granted U.S. Patent No. 7,268,227.  The '227 patent is the second U.S. patent to be awarded to the Rehovot, Israel-based biopharmaceutical company.  According to the statement released by Proteologics, the '227 patent encompasses siRNA molecules that inhibit the expression of the antiviral drug target, hPOSH (human Plenty Of SH3 domains protein), a ubiquitin ligase that Proteologics identified as being essential for HIV biogenesis.

Proteologics' research focuses primarily on the discovery of inhibitors for specific ubiquitin enzymes -- E3 ligases -- and their interacting proteins, and the therapeutic use of such inhibitors.  Ubiquitin enzymes are known to play key roles in a variety of cell cycle and viral processes.  Dr. Avram Hershko and Dr. Aaron Ciechanover, who lead Proteologics' scientific advisory board, were awarded the 2004 Nobel Prize in chemistry, along with Dr. Irwin Rose, for their discovery of the ubiquitin system.

The ubiquitin system, in which proteins are covalently modified with ubiquitin (at left), is responsible for regulating most eukaryotic cellular processes, including transcriptional and cell cycle regulation, DNA repair, signal transduction, immune response, protein quality control, and metabolism.  This system of regulation is carried out by three enzymes (see figure below):  E1, a ubiquitin-activating enzyme; E2, a ubiquitin-conjugating enzyme; and E3, a ubiquitin ligase that specifically recognizes proteins for ubiquitination and recruits E2 for the conjugation of ubiquitin.  Human E3, rather than being a single protein, is actually a family of hundreds of distinct proteins, each of which targets a small set of proteins for ubiquitination.  As a result of the essential physiological role of ubiquitination and the high degree of substrate specificity of the individual members of the E3 family, E3 ligases constitute attractive therapeutic targets.

Proteologics' '227 patent issued from U.S. Application No. 11/031,737, filed January 7, 2005, which is a divisional of U.S. Application No. 10/293,965, filed November 12, 2002, which issued as U.S. Patent No. 7,250,250, and which claims the benefit of U.S. Provisional Application Nos. 60/345,846, filed November 9, 2001, and No. 60/364,530, filed March 15, 2002.  Representative independent claim 1 of the '227 patent recites:

1.  A composition comprising:
    (a) a first nucleic acid which
        (i) comprises between 5 and 100 nucleotides, of SEQ ID NO: 1 or a complement thereof, and
        (ii) decreases the level of a POSH mRNA and/or a POSH polypeptide when introduced into a cell, and
    (b) a pharmaceutically acceptable excipient.

Ubiquitin-mediated protein degradation:

1.  The E1 enzyme activates the ubiquitin molecule. This reaction requires energy in the form of ATP.
2.  The ubiquitin molecule is transferred to a different enzyme, E2.
3.  The E3 enzyme can recognise the protein target which is to be destroyed.  The E2-ubiquitin complex binds so near to the protein target that the actual ubiquitin label can be transferred from E2 to the target.
4.  The E3 enzyme now releases the ubiquitin-labelled protein.
5.  This last step is repeated until the protein has a short chain of ubiquitin molecules attached to itself.
6.  This ubiquitin chain is recognised in the opening of the proteasome.  The ubiquitin label is disconnected and the protein is admitted and chopped into small pieces.

(Graphic and text from Figure 2, "Information for the Public," Nobelprize.org, October 6, 2004)

Patent Profile: Cyplasin Biomedical Announces Issuance of Patent for Protein Based Cancer Treatment

    By Kwame Mensah --

Last November, Cyplasin Biomedical Ltd. announced that it had been granted U.S. Patent No. 7,271,242, entitled "Cytotoxic Cyplasin of the SeaHare, Aplysia punctata, cDNA Cloning and Expression of Bioreactive Recombinants."  The '242 patent covers the production of cytotoxic cyplasin by mammalian cells and the use of this protein for treating cancer.  According to Cyplasin's Chief Scientific Officer Professor Christian Petzelt the company will use the technology encompassed by the '242 patent, as well as that encompassed by another Cyplasin patent issued in 2001 (U.S. Patent No. 6,171,818), to further develop cyplasin's selective ability to rapidly kill certain types of cancer cells while leaving normal non-cancerous cells untouched.

The '242 patent issued from U.S. Application No. 10/501,098, filed December 18, 2002.  Representative claims 1, 2, and 4 of the '242 patent recite:

1.  An isolated protein encoded by a nucleic acid molecule selected from the group consisting of: a) a nucleic acid molecule encoding a protein comprising the amino acid sequence from position 20 or 53 to 558 of SEQ ID NO: 1; b) a nucleic acid molecule comprising the sequence of SEQ ID NO: 5; and c) a nucleic acid molecule, the sequence of which deviates from the nucleic acid sequences specified in (a) or (b) due to the degeneration of the genetic code, wherein said protein lacks a functional secretory signal sequence.

2.  A pharmaceutical composition comprising a protein of claim 1.

4.  The protein of claim 1, wherein the protein is cyplasin with a deleted or non-functional signal sequence.

Patent Profile: stART Licensing Announces Issuance of Patents for Cloning Ungulates

    By Donald Zuhn --

Last month, stART Licensing, Inc. announced that it had been granted U.S. Patent Nos. 7,304,204 and 7,307,198.  stART Licensing, Inc., an Austin, Texas-based joint venture between Geron Corp. and Exeter Life Sciences, Inc., manages and licenses a portfolio of patent rights related to animal reproductive technologies (including patents encompassing technology originally developed by the Roslin Institute for the cloning of Dolly the sheep (at right)).

The '204 and '198 patents, which are assigned to the Roslin Institute, relate to methods of cloning ungulate animals (hoofed mammals), fetuses, and embryos using differentiated cells.  The patents -- the eighth and ninth U.S. patents to be awarded to the Roslin Institute -- are part of a portfolio of patents and applications that the Roslin Institute has exclusively licensed to stART for non-human animal cloning applications.

According to stART's statement, the Roslin Institute also expects to secure two additional patents from related U.S. Application Nos. 09/650,194 and 09/989,126, for which the U.S. Patent and Trademark Office recently issued notices of allowance.  stART noted that the allowance of the '194 and '126 applications was the result of successful interference proceedings between those applications and U.S. Patent Nos. 5,945,577 and 6,235,970, which are assigned to the University of Massachusetts and exclusively licensed to Advanced Cell Technology.  stART Chairman Jonathan Thatcher stated that "[t]he technology covered by the Roslin patents and patent applications has been widely adopted," and "has been used to clone a broad range of species including cattle, sheep, pigs, goats, horses, mice, rats, rabbits, cats and dogs."

The '204 and '198 patents issued from U.S. Application Nos. 09/989,125 and 09/989,128, respectively, both of which claim the benefit of U.S. Application Nos. 09/650,285 and 08/803,165 (the latter of which issued as U.S. Patent No. 6,252,133), International Application No. PCT/GB96/02098, and British application GB 9517779.6.  Representative independent claims 1 and 12 of the '204 patent recite:

1.  A method of cloning an ungulate by nuclear transfer comprising:
    (i) inserting a nucleus of an ungulate differentiated somatic cell, which has passed start in the mitotic cell cycle and is in the G1 phase of the cell cycle, into an unactivated, metaphase II-arrested, ungulate enucleated oocyte of the same species to reconstruct an embryo;
    (ii) maintaining the reconstructed embryo without activation for a sufficient time to allow the reconstructed embryo to become capable of developing to term;
    (iii) activating the resultant reconstructed embryo;
    (iv) culturing said activated, reconstructed embryo; and
    (v) transferring said cultured, reconstructed embryo to a host ungulate of the same species such that the reconstructed embryo develops to term.

12.  A method of cloning an ungulate fetus by nuclear transfer comprising:
    (i) inserting a nucleus of an ungulate differentiated somatic cell, which has passed start in the mitotic cell cycle and is in the G1 phase of the cell cycle, into an unactivated, metaphase II-arrested, ungulate enucleated oocyte of the same species to reconstruct an embryo;
    (ii) maintaining the reconstructed embryo without activation for a sufficient time to allow the reconstructed embryo to become capable of developing to term;
    (iii) activating the resultant reconstructed embryo;
    (iv) culturing said activated, reconstructed embryo; and
    (v) transferring said cultured, reconstructed embryo to a host ungulate of the same species such that the reconstructed embryo develops into a fetus.

Representative independent claims 1, 14, and 17 of the '198 patent recite:

1.  A method of cloning a pig, comprising:
    (i) inserting a nucleus of a differentiated pig cell, which is in the G1 phase of the cell cycle, into an unactivated, enucleated, metaphase II-arrested, pig oocyte, to reconstruct an embryo;
    (ii) maintaining the reconstructed embryo without activation for a sufficient time to allow the reconstructed embryo to become capable of developing to term;
    (iii) activating the resultant reconstructed embryo; and
    (iv) transferring said reconstructed embryo to a host pig such that the reconstructed embryo develops into a fetus,
    wherein the fetus is capable of developing to term.

14.  A method of cloning a pig, comprising:
    (i) inserting a nucleus of a cultured, differentiated pig embryonic disc cell, which is in the G1 phase of the cell cycle, into an unactivated, enucleated, metaphase II-arrested, pig oocyte, to reconstruct an embryo;
    (ii) maintaining the reconstructed embryo without activation for a sufficient time to allow the reconstructed embryo to become capable of developing to term;
    (iii) activating the resultant reconstructed embryo; and
(iv) transferring said reconstructed embryo to a host pig such that the reconstructed embryo develops into a fetus,
    wherein the fetus is capable of developing to term.

17.  A method of producing an ungulate embryo by nuclear transfer comprising:
    (i) transfer of a nucleus of an ungulate cell, which has passed start in the mitotic cell cycle and is in the G1 phase of the cell cycle, into an unactivated, enucleated, metaphase II-arrested ungulate oocyte of the same species;
    (ii) activation of the recipient oocyte containing the donor cell nucleus; and
    (iii) incubation of the activated oocyte to provide an embryo;
    wherein the donor cell nucleus is from an ungulate differentiated cell.

Patent Profile: Morphotek Announces Issuance of Patent for Genetically Altered Antibodies

    By Suresh Pillai --

Last month, Morphotek, Inc., a subsidiary of Eisai Co., Ltd. based in Exton, Pennsylvania, announced that it had been granted U.S. Patent No. 7,235,643 ("Antibodies and methods for generating genetically altered antibodies with high affinity," issued June 26, 2007).  This is the eleventh U.S. Patent awarded to Morphotek, Inc.

Prior to cell division, gene duplication is accomplished by the parent cell's replication of the cell's genetic material.  Errors in replication can lead to mutations among the duplicated genes; however, DNA repair mechanisms, such as mismatch repair (MMR), normally repair such mutations prior to cell division.  MMR is a proofreading mechanism by which the cell checks the genetic coding between the two copies of the genetic material to ensure that the genes are, in fact, copies of one another.  Normally, cell division occurs only upon completion of MMR.  In cells where MMR is dysfunctional, mutations accumulate through the genome to the point where sibling cells have traits different from the parents.  Morphogenics is a technology whereby the MMR process is selectively regulated within a living host.  Through the regulation of morphogenics and targeted mutation, scientists can accelerate cellular evolution, thereby creating unique organisms ideal for the study of disease pathogenesis or other commercial applications.

The '643 patent covers both Morphotek's proprietary human MORPHODOMA® technology, which combines an ex vivo immunization with morphogenics.  The resultant antibodies naturally target specific disease-associated antigens.

The '643 patent issued from U.S. Application No. 10/243,130 which was filed on September 13, 2002 and which was a continuation-in-part of U.S. Application No. 09/707,468, filed November 7, 2000, which is now U.S. Patent No. 6,808,894.  Independent claim 1 recites:

1.  A method for producing a monoclonal antibody having an increased affinity for the antigen to which it binds relative to a monoclonal antibody comprising a heavy chain variable region comprising SEQ ID NO: 18, the method comprising substituting Alanine at the sixth position of SEQ ID NO:18 with Proline, whereby the affinity of the produced monoclonal antibody for said antigen is increased.

Suresh Pillai, Ph.D., is a molecular biologist and a third-year law student at DePaul University College of Law.  Dr. Pillai was a member of MBHB's 2007 class of summer associates, and is currently working as a law clerk at MBHB.

Patent Profile: Vaccinex Announces Issuance of European Patent Covering ActivMAb® Antibody Discovery Technology

    By Donald Zuhn --

Last Friday, Vaccinex, Inc. announced that it had been granted European Patent No. 1 340 088.  According to the statement released by Vaccinex, the '088 patent covers the Rochester, New York-based company's ActivMAb® antibody discovery technology platform, which can be used for the discovery and development of new monoclonal antibody therapies, and which Vaccinex has used to identify four of its lead therapeutic antibodies.

Vaccinex President and CEO Dr. Maurice Zauderer stated that "[t]his European patent, and related patents already awarded in the United States and elsewhere, underscores the novelty of our discovery technology, which gives Vaccinex important advantages over competitors in the area of therapeutic antibodies."  Vaccinex estimates that the market for antibody therapies in 2007 will be $25 billion, and projects the market to reach $43 billion by 2012.

Vaccinex describes its ActivMAb® technology as allowing for the direct selection of high-affinity, fully human antibodies using a unique vaccinia virus-based vector to express antibodies in mammalian cells, thereby providing extremely high levels of combinatorial diversity of immunoglobulin heavy and light chains.  A video outlining Vaccinex' antibody technology can be viewed here.  Representative independent claim 1 of the '088 patent recites:

1.  An in vitro method of selecting polynucleotides which encode an antigen-specific immunoglobulin molecule, or antigen-specific fragment thereof, comprising:

(a)  introducing into a population of eukaryotic host cells capable of expressing said immunoglobulin molecule a first library of polynucleotides encoding, through operable association with a transcriptional control region, a plurality of first immunoglobulin subunit polypeptides, each first immunoglobulin subunit polypeptide comprising:

(i)  a first immunoglobulin constant region selected from the group consisting of a heavy chain constant region and a light chain constant region,
(ii)  an immunoglobulin variable region corresponding to said first constant region, and
(iii)  a signal peptide capable of directing cell surface expression or secretion of said first immunoglobulin subunit polypeptide;

(b)  introducing into said host cells a second library of polynucleotides encoding, through operable association with a transcriptional control region, a plurality of second immunoglobulin subunit polypeptides, each comprising:

(i)  a second immunoglobulin constant region selected from the group consisting of a heavy chain constant region and a light chain constant region, wherein said second immunoglobulin constant region is not the same as said first immunoglobulin constant region,
(ii)  an immunoglobulin variable region corresponding to said second constant region, and
(iii)  a signal peptide capable of directing cell surface expression or secretion of said second immunoglobulin subunit polypeptide, wherein said second immunoglobulin subunit polypeptide is capable of combining with said first immunoglobulin subunit polypeptide to form an immunoglobulin molecule, or antigen-specific fragment thereof;

(c)  permitting expression of immunoglobulin molecules, or antigen-specific fragments thereof, from said host cells;
(d)  contacting said immunoglobulin molecules with an antigen; and
(e)  recovering those polynucleotides of said first library which express immunoglobulin molecules, or antigen-specific fragments thereof, specific for said antigen.

Patent Profile: Metagenics Awarded Three U.S. Patents For Anti-Inflammatory Compounds

    By Suresh Pillai --

Metagenics, Inc. of San Clemente, California has been awarded U.S. Patent Nos. 7,270,835 ("Compositions that treat or inhibit pathological conditions associated with inflammatory response," issued September 18, 2007);  7,195,785 ("Complex mixtures exhibiting selective inhibition of cyclooxygenase-2," issued March 27, 2007) and 7,205,151 (same title, issued April 17, 2007), three patents that cover discoveries relating to selective kinase response modifiers that have anti-inflammatory properties.  These patents extend to thirty the number of U.S. Patents awarded to both Metagenics, Inc. and its Metaproteomics® Nutrigenomics Research Center subsidiary.

Inflammation via the cyclooxygenase pathway (COX-2) contributes to numerous maladies, including osteoarthritis, reduction of bone mineral density, and autoimmune disease.  COX-2 also plays a housekeeping role within certain cellular pathways; therefore, any treatment targeted to inhibit COX-2-mediated inflammation should not similarly inhibit COX-2-mediated cellular housekeeping.  One method for targeted regulation of COX-2 pathways is through the use of selective kinase response modifiers (SKRMs).  SKRMs inhibit the induction of inflammation via the selective alteration of COX-induced signaling cascade phosphorylation profiles.  The primary benefit of using SKRMs is that, although the inflammation pathways are inhibited, other COX-mediated signaling pathways, including those responsible for normal cellular housekeeping tasks, remain intact.

The '835 patent covers both Metagenics' proprietary compound Luduxin, which consists of rho iso-alpha acids derived from hops, and the use of Luduxin in preserving joint health.  The '785 and '151 patents cover both Metagenics' proprietary compound Tetrase, which consists of tetrahydro-isohumulone (a tetrahydro iso-alpha acid derived from hops), and the use of Tetrase in supporting the management of inflammation.

The '835 patent issued from U.S. Application No. 10/689,856, which was filed on October 20, 2003, and which claims the benefit of Provisional Application No. 60/420,383, filed October 21, 2002.  Independent claim 1 recites:

1.  A method of preserving the health of joint tissues comprising administering to a patient, group consisting of oleanolic acid and ursolic acid, and a component selected from the group consisting of rosemary, an extract derived from rosemary, and a compound derived from rosemary.

The '785 patent issued from U.S. Application No. 10/480,145, which was filed on June 20, 2002.  Independent claim 1 recites:

1.  A method of treating inflammation comprising administering to an animal suffering symptoms of inflammation a pharmaceutical grade extract of hops comprising an effective amount of tetrahydroisohumulone, and an effective amount of essential oils, fats or waxes, wherein said administration provides about 0.01 to 100 mg per kg body weight per day of tetrahydroisohumulone.

The '151 patent issued from U.S. Application No. 09/885,721, which was filed on June 20, 2001.  Independent claim 1 recites:

1.  A composition comprising a pharmaceutical grade extract of hops comprising an effective amount of tetrahydroisohumulone, and an effective amount of at least one component selected from the group consisting of essential oils, fats and waxes, wherein said pharmaceutical grade extract provides 15 to 45 weight % of tetrahydroisohumulone of the composition.

Suresh Pillai, Ph.D., is a molecular biologist and a third-year law student at DePaul University College of Law.  Dr. Pillai was a member of MBHB's 2007 class of summer associates, and is currently working as a law clerk at MBHB.

Patent Profile: Avicena Group Announces Issuance of Patent for ALS Therapeutic

    By Donald Zuhn --

Last week, Avicena Group, Inc. announced that it had been granted U.S. Patent No. 7,285,573.  The '573 patent, which relates to use of creatine (lower left) and creatine phosphate (lower right) for treating amyotropic lateral sclerosis (ALS) or "Lou Gehrig's Disease," is the fifth U.S. patent to be awarded to the Palo Alto, California-based biotech company.

According to the statement released by Avicena, the '573 patent "provides further protection for the Company's growing portfolio of drug candidates for the treatment of ALS, which are designed to slow disease progression and improve the quality of life for patients."  Among Avicena's ALS drug candidates are AL-02 and AL-08, which have been the subjects of Phase II/III trials conducted by the Northeast ALS Consortium (NEALS), Carolinas Medical Center, and Utrecht University.  The results of these trials indicate that Avicena's ALS drug candidates show a 1.47-fold increase in median survival compared to results in patients taking a placebo.  Avcena Chairman and CEO Dr. Belinda Tsao Nivaggioli stated that the company was "very excited about the prospects of AL-02 for the treatment of ALS" and was currently preparing for confirmatory Phase III trials in early 2008.

The '573 patent issued from U.S. Application No. 10/718,846, filed November 21, 2003, and claims the benefit of U.S. Application No. 08/853,174 (which issued as U.S. Patent No. 6,706,764), which was a national stage application of International Application No. PCT/US95/14567, which claims the benefit of U.S. Application No. No. 08/336,388, filed November 8, 1994.  Representative independent claims 1, 3, 5, and 7 of the '573 patent recite:

1.  A method for treating a subject afflicted with amyotrophic lateral sclerosis, comprising administering to the subject an amount of creatine, such that the subject is treated for amyotrophic lateral sclerosis.

3.  A method for treating a subject afflicted with amyotrophic lateral sclerosis, comprising administering to the subject an amount of creatine phosphate, such that the subject is treated for amyotrophic lateral sclerosis.

5.  A method for reducing progression of amyotrophic lateral sclerosis in a subject, comprising administering to the subject an amount of creatine, such that the progression of amyotrophic lateral sclerosis in said subject is reduced.

7.  A method for reducing progression of amyotrophic lateral sclerosis in a subject, comprising administering to the subject an amount of creatine phosphate, such that the progression of amyotrophic lateral sclerosis in said subject is reduced.

Patent Profile: CellCyte Genetics Announces Issuance of Patent on Stem Cell Delivery Method

    By Donald Zuhn --

Last week, CellCyte Genetics announced that it had been granted U.S. Patent No. 7,282,222, which relates to methods for delivering stem cells to a target tissue in a mammal using glycoconjugate to traffic the cells to a desired organ.  According to CellCyte's press release, the Kirkland, Washington based biotech company, which has exclusively licensed the '222 patent from the U.S. Department of Veterans Affairs, plans to use the patented technology to develop stem cell enabling therapeutic products for efficient delivery and significantly increased retention of adult stem cells to target organs such as the heart.

CellCyte's first product in development, CCG-TH30, is designed to target autologous bone-marrow-derived (adult) stem cells to the heart of patients after a heart attack/  CellCyte Chief Scientific Officer Dr. Ronald Berninger noted that CCG-TH30 has been shown in preclinical models to increase stem cell retention to 77% as opposed to the 6% retention level of conventional methods.  In addition, unlike conventional methods that require an invasive procedure, CCG-TH30 can be delivered intravenously.  A video outlining the CellCyte's technology can be viewed here.

The '222 patent issued from U.S. Application No. 10/388,964, filed March 14, 2003, and claims the benefit of U.S. Provisional Application No. 60/364,498, filed March 15, 2002.  Representative independent claims 1, 3, 5, and 7 of the '222 patent recite:

1.  A method for targeting a hematopoietic stem cell to the heart of a mammal comprising administering an asialoorosomucoid to the mammal prior to administration of the cell to the mammal, whereby the cell is directed to the heart.

3.  A method for targeting a mesenchymal stem cell to the heart of a mammal comprising administering an orosomucoid to the mammal prior to administration of the cell to the mammal, whereby the cell is directed to the heart.

5.  A method for targeting a hematopoietic stem cell to the liver of a mammal comprising administering an orosomucoid to the mammal prior to administration of the cell to the mammal, whereby the cell is directed to the liver.

7.  A method for targeting a mesenchymal stem cell to the liver of a mammal comprising administering an asialoorosomucoid to the mammal prior to administration of the cell to the mammal, whereby the cell is directed to the liver.

Patent Profile: Nventa Biopharmaceuticals Corp. Announces Grant of U.S. Patent 7,262,014 to HPV-Fusion Technology

    By Christopher P. Singer --

Nventa Biopharmaceuticals Corporation announced on October 29, 2007 that U.S. Patent 7,262,014, titled "Immune responses against HPV antigens elicited by compositions comprising an HPV antigen and a stress protein or an expression vector capable of expression of these proteins" has been granted by the U.S. Patent and Trademark Office.  The '014 patent relates to compositions and methods for inducing or enhancing immune response to human papillomavirus (HPV) with or without adjuvant.  According Nventa's press release, the patent provides a method for treating a tumor expressing HPV antigen by administering an effective amount of a composition of an HPV antigen fused to a stress protein, and additionally provides exclusivity for HspE7, an investigational therapeutic vaccine.

The '014 patent issued from U.S. Application No. 10/938,695 (filed September 10, 2004) and claims priority through a number of divisional and continuation applications as well as to a provisional application, filed on August 5, 1997.  The patent contains a total of 15 claims relating to methods of treatment.  Representative independent Claims 1 and 3 recite:

1.  A method of treating a tumor exhibiting an HPV protein antigen, the method comprising administering to a subject having the tumor an effective amount of an expression vector that encodes and is capable of directing expression of a fusion protein comprising the HPV protein antigen fused to a stress protein.

3.  A method of treating a tumor expressing an HPV protein antigen, the method comprising administering to a subject an effective amount of a composition comprising the HPV protein antigen joined to a stress protein.

Patent Profile: Ryogen Announces Issuance of Patent on Soluble Aminopeptidase P Gene

    By Donald Zuhn --

Ryogen LLC announced today that it had been granted U.S. Patent No. 7,273,718.  The '718 patent, which relates to an isolated genomic polynucleotide fragment that encodes human soluble (cytosolic) aminopeptidase P, appears to be the Suffern, New York-based genomics company's second U.S. patent.  According to Ryogen's website, the company, which is a portfolio company of IP Holdings LLC, was formed for the purpose of licensing U.S. Patent No. 6,399,349, which is directed to the human aminopeptidase P gene.

The '718 patent issued from U.S. Application No. 10/457,715, filed June 9, 2003, and claims the benefit of U.S. Provisional Application No. 60/386,941, filed June 7, 2002.  Representative independent claims 1 and 8 of the '718 patent recite:

1.  An isolated genomic polynucleotide, wherein said polynucleotide can be isolated from human chromosome 10 and is selected from the group consisting of:
    (a) a polynucleotide consisting of the nucleic acid sequence set forth in SEQ ID NO:2,
    (b) a polynucleotide consisting of the sequence of nucleotides from position 12803 to position 55760 of SEQ ID NO:2, and
    (c) a polynucleotide which is the complement of a polynucleotide of (a) or (b) and encodes a polypeptide having aminoacyl prolyl peptidyl hydrolase activity.

8.  An isolated polynucleotide consisting of a nucleic acid sequence selected from the group consisting of
    (a) a sequence of at least 5000 contiguous nucleotides within the region consisting of the sequence of nucleotides from position 1 through position 12802 of SEQ ID NO:2,
    (b) a sequence of at least 2000 contiguous nucleotides within the region consisting of the sequence of nucleotides from position 55761 through position 58735 of SEQ ID NO:2,
    (c) a sequence of nucleotides complementary to the nucleotide sequence of (a), and
    (d) a sequence of nucleotides complementary to the nucleotide sequence of (b).

Patent Profile: Epigenomics Awarded Patent Covering DNA Methylation Detection Method

    By Suresh Pillai --

Epigenomics AG of Frankfurt, Germany has been awarded U.S. Patent No. 7,229,759 ("Highly sensitive method for the detection of cytosine methylation patterns," issued June 12, 2007).  The '759 patent, covering a method for the detection of cytosine methylation in genomic DNA samples, is the fourteenth U.S. patent to be awarded to the Frankfurt, Germany-based biotech company.

DNA methylation is a naturally occurring means by which cells regulate gene transcription.  Methylation occurs when cytosine is modified via the addition of a DNA methyl group.  The methyl group subsequently interferes with the binding of transcription factors and allows for chromatin condensation, thereby terminating gene activity.  Specific methylation at cytosines throughout the genome results in the specific targeted reduction for gene transcription.  Methylation patterns also form genetic fingerprints specific to various disease states, including cancer, that correspond to the regulation of genes important in disease pathogenesis.

The newly issued patent covers Epigenomics' HeavyMethyl® and MethyLight® technology (see below) as well as their proprietary line of DNA methylation biomarkers.  Through the use of established real-time quantitative PCR techniques, the technology can differentiate between genomic DNA that is either methylation-modified or unmodified.  This technology can be used for the high-throughput methylation detection of cancer biomarkers, thereby providing a clinical diagnostic tool for the early detection of cancer at the genetic level.

The '759 patent issued from U.S. Application No. 10/229,370, which was filed on August 27, 2002, and which claims the benefit of International Application No. PCT/EP02/02572, filed March 8, 2002.  Independent claim 1 recites:

1.  A method for the detection of cytosine methylation in DNA samples, characterized in that the following steps are conducted:
    a genomic DNA sample, which comprises the DNA to be investigated as well as background DNA, is chemically treated in such a way that all unmethylated cytosine bases are converted to uracil, while 5-methylcytosine bases remain unchanged;
    the chemically treated DNA sample is amplified with the use of at least 2 primer oligonucleotides, as well as a polymerase and at least one blocking oligonucleotide or PNA oligomer which preferentially binds to a 5'-CG-3' dinucleotide or a 5'-TG-3' dinucleotide or a 5'-CA-3' dinucleotide on the background DNA, whereby the DNA to be investigated is preferentially amplified over the background DNA as the template, and
    the amplified products are analyzed and the methylation status in the DNA to be investigated is concluded from the presence of an amplified product and/or from the analysis of the amplified product.

Suresh Pillai, Ph.D., is a molecular biologist and a third-year law student at DePaul University College of Law.  Dr. Pillai was a member of MBHB's 2007 class of summer associates, and is currently working as a law clerk at MBHB.