Ex Parte Blau et alDownload PDFPatent Trial and Appeal BoardMay 23, 201713440534 (P.T.A.B. May. 23, 2017) Copy Citation United States Patent and Trademark Office UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O.Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/440,534 04/05/2012 Helen M. Blau STAN-829 6495 77974 7590 05/25/2017 Stanford University Office of Technology Licensing Bozicevic, Field & Francis LLP 201 REDWOOD SHORES PARKWAY SUITE 200 REDWOOD CITY, CA 94065 EXAMINER VISONE, THOMAS J ART UNIT PAPER NUMBER 1651 NOTIFICATION DATE DELIVERY MODE 05/25/2017 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): docket@bozpat.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte HELEN M. BLAU, BENJAMIN D. COSGROVE, and PENNEY M. GILBERT Appeal 2016-005788 Application 13/440,534 Technology Center 1600 Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and JOHN E. SCHNEIDER, Administrative Patent Judges. MILLS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35U.S.C. § 134. The Examiner has rejected the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. Appeal 2016-005788 Application 13/440,534 STATEMENT OF CASE The following claims are representative. 1. A method for improving the ability of aged, muscle satellite cells to regenerate muscle tissue in an individual human past the age 50 years or mouse past 22 months of age, the method comprising: identifying an aged individual mouse or human; contacting aged muscle satellite cells from said aged individual with an inhibitor of p38 mitogen-associated protein kinase (MAPK); wherein said the aged muscle satellite cells are induced to proliferate and regenerate said tissue. 4. The method according to Claim 1, wherein said inhibitor of p38 MAPK is administered locally or systemically to the individual. 16. A method for improving the ability of aged human or mouse muscle satellite cells to regenerate muscle tissue in response to injury, the method comprising: identifying an aged individual mouse or human past the age 50 years in a human or 22 months in a mouse; contacting a population of aged human or mouse muscle satellite cells obtained from an the aged individual, in an ex vivo culture on a pliable substrate with an inhibitor of p38 mitogen associated protein kinase (MAPK) in a dose and for a time sufficient to expand the number of muscle satellite cells in the population; wherein the expanded population of aged muscle satellite cells has an enhanced ability to regenerate muscle tissue relative to untreated aged muscle satellite cells. 18. The method of Claim 16, wherein said pliable substrate is a hydrogel. 2 Appeal 2016-005788 Application 13/440,534 Grounds of Rejection 1. Claims 1—2, 4—5, 13, 16, 20, and 26 are rejected under pre-AIA 35 U.S.C. §103(a) as being unpatentable over Underhill (WO 02/094842 A2; pub. Nov. 28, 2002). 2. Claims 18 is rejected under 35 U.S.C. § 103(a) as being unpatentable over Underhill and Cosgrove (Benjamin D. Cosgrove, A home away from home: challenges and opportunities in engineering in vitro muscle satellite cell niches, NIH Public Access Author Manuscript, Author manuscript available in Differentiation, 2009; 782(2—3). FINDINGS OF FACT The Examiner’s findings of fact are set forth in the Final Action at pages 2—7. The following facts are highlighted. 1. Underhill teaches a method that can be used to regenerate muscle in a variety of subjects such as fetuses, newborns, children, and adults. (Page 27, lines 26—29). More particularly, Underhill teaches the method can be used to treat late-adult onset Welander distal myopathy and repair or replace, i.e., regenerate, muscle tissue (Pages 27—29). 2. Underhill states that In another embodiment, the muscle atrophy results from chronic disuse. Such disuse atrophy may stem from conditions including, but not limited to: paralysis due to stroke, spinal cord injury; skeletal immobilization due to trauma (such as fracture, sprain or dislocation) or prolonged bed rest. In yet another embodiment, the muscle atrophy results from metabolic stress or nutritional insufficiency, including, but not limited to, the cachexia of cancer and other chronic illnesses, fasting or rhabdomyolysis, endocrine disorders such as, but not limited to, disorders of the thyroid gland and diabetes. p. 32. 3 Appeal 2016-005788 Application 13/440,534 3. Underhill states that its p38 mitogen activated protein kinase (MAPK) inhibitor compounds may be administered systemically or topically. P.38. 4. Underhill recognizes the myogenic potential of progenitor cells in any phase of development, including aged cells, can be enhanced through p38 MAPK inhibition. Final Act. 3. 5. Underhill explicitly teaches that “inhibition of p38 MAPK activity results in enhanced myogenesis of myogenic precursors.” (Page 3, lines 21—23). The starting cells and method steps taught by Underhill are indistinguishable from those of the claimed invention. Id. 6. According to the Specification, “Muscle tissue in adult vertebrates regenerates from stem cells known as satellite cells. Satellite cells are distributed throughout muscle tissue and are mitotically quiescent in the absence of injury or disease, residing in an instructive, anatomically defined niche.” Spec. 1. 7. According to Appellants’ Specification, page 3, In one embodiment of the invention, a subject who is in need of tissue rejuvenation, e.g. due to an injury, disease, or aging, is contacted with an inhibitor of the p38 mitogen associated protein kinase (MAPK) signaling pathway in a dose effective to stimulate rejuvenation and proliferation of stem cells resident in the targeted tissue. Included as inhibitors of interest are molecules that selectively inhibit p38 MAPK, a component of the MAPK signaling pathway, or a component upstream or downstream of the MAPK signaling pathway. Inhibitors of interest may be small molecules, polynucleotides, antibodies, antagonist proteins, and the like. Inhibitors of interest include, without limitation, small molecule inhibitors of the a and P isoforms of p38 MAP kinase, e.g. SB202190, SB203580, etc. Delivery of the inhibitor may be systemic or localized, usually localized. 4 Appeal 2016-005788 Application 13/440,534 8. According to the Specification, “In some embodiments, the tissue is muscle tissue. Resident in muscle tissue are satellite cells, which are stem cells that ultimately give rise to muscle fibers. Satellite cells in aged muscle are rejuvenated and capable of regeneration of tissue when the p38 MAPK signaling pathway is inhibited.” Spec. 3. PRINCIPLES OF LAW In making our determination, we apply the preponderance of the evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427 (Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings before the Office). “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Obviousness Rejection 1 Appellants do not provide separate arguments for individual claims. We select claims 1 and 18 as representative of rejections 1 and 2, respectively. According to the Examiner, Underhill teaches a method of regenerating muscle tissue comprising contacting myogenic progenitor cells with a p38 (e.g., alpha and beta isoforms) MAPK inhibitor to induce myogenesis and then administering the cells to a subject. (Page 2, lines 13-34; page 5, lines 25- 27; page 10, lines 16-25; page 3, lines 21-32; and pages 26-28). Alternatively, Underhill teaches the p3 8 MAPK inhibitor can be directly administered to a subject’s tissue in order to induce the myogenic progenitor cells residing in the tissue. (Page 26, lines 15-30; and page 37, lines 24-34)[.] 5 Appeal 2016-005788 Application 13/440,534 Underhill teaches the precursors may be stimulated to proliferate using, e.g., BMP-4 or any other known growth or proliferative factor for myogenic progenitors. (Page 28, lines 11-12). Underhill also teaches the treatment can be administered by orally, by parenteral administration by injection, or by IM injection. (Pages 37-40). Underhill teaches the myogenic progenitor cells can be cultured on pliable substrates and subsequently transplanted into a subject. (Pages 28-29). It is noted that Underhill broadly defines “myogenic progenitor” and “myogenic precursor” cells as any cell that is capable of becoming confined to the muscle fate or giving rise to a descendent cell confined to the muscle fate. (Page 5, lines 25- 28). Underhill does not explicitly teach the muscle tissue is from an individual human or mouse past the age 50 years in a human or past 22 months in a mouse. Final Act. 2—3. Appellants contend that, “Underhill cannot render the claims . . . obvious at least because Underhill fails to teach or suggest a limitation of Claim 1, namely contacting aged muscle satellite cells of an aged individual with an inhibitor of p38 MAPK.” App. Br. 4. Appellants further contend that, the Examiner has erred in his interpretation of how an ordinary skilled artisan would interpret the teachings of Underhill. Underhill describes at length how prior studies performed in cells derived from satellite cells showed that “activation of p38 MAPK stimulates myogenesis” (see e.g., pg. 3, line 24-29; emphasis added). In addition, as described above, the specifically described embodiments of Underhill are restricted to the application of p38 MAPK inhibitor to developing embryonic limbs. Underhill, however, does not suggest that the findings made in studying embryonic cells somehow translate to adult satellite cells. In fact, Underhill 6 Appeal 2016-005788 Application 13/440,534 suggests the opposite, stating that satellite cells are important in “a program that differs from the embryonic myogenic program ” (pg.5, lines 10-11; emphasis added). Furthermore, Underhill suggests that the myogenesis promoting effect of p3 8 MAPK inhibitor is not even consistent in embryonic cell types across different conditions. App. Br. 5. ANALYSIS We agree with the Examiner’s fact finding, statement of the rejection and responses to Appellants’ arguments as set forth in the Answer. We find that the Examiner has provided evidence to support a prima facie case of obviousness. We provide the following additional comment to the Examiner’s argument set forth in the Final Rejection and Answer. We are not persuaded by Appellants’ arguments. During ex parte prosecution, claims are to be given their broadest reasonable interpretation consistent with the description of the invention in the specification. See In re Zletz, 893 F.2d 319, 321 (Fed. Cir. 1989). Appellants’ claims encompass administering an inhibitor of the p38 mitogen associated protein kinase (MAPK) systemically to an adult. FF7, claim 4. Appellants’ Specification states that, “the tissue is muscle tissue. Resident in muscle tissue are satellite cells, which are stem cells that ultimately give rise to muscle fibers. Satellite cells in aged muscle are rejuvenated and capable of regeneration of tissue when the p38 MAPK signaling pathway is inhibited.” FF8. Underhill discloses administering an inhibitor of the p38 mitogen associated protein kinase (MAPK) systemically to adults with muscle atrophy. In particular, to adults with muscular atrophy conditions that are 7 Appeal 2016-005788 Application 13/440,534 often associated with aging, e.g, stroke, diabetes, etc. FF1, 2. Because satellite cells are resident in muscle tissue, the administration of an inhibitor of the p38 mitogen associated protein kinase (MAPK) systemically to adults with muscle atrophy in Underhill, necessarily meets the method limitations claimed, as muscle tissue will be exposed to the systemically administered inhibitor of the p38 mitogen associated protein kinase (MAPK) in Underhill (cf Instant claim 5). In addition, based on the Examiner’s argument on page 5 of the Answer, we agree with the Examiner that, “muscle satellite cells, i.e., muscle stem cells that progress through the myogenic linage to give rise to terminally differentiated muscle tissue, are consistent with the definition of myogenic progenitors and myogenic precursors taught by Underhill.” The Examiner further finds that, “Applicant discloses that ‘[mjuscle tissue in adult vertebrates will regenerate from reserve myoblasts called “satellite cells”.’ (10087). Indeed, Underhill even teaches contacting myocytes, in addition to, precursors of myocytes, such as mesenchymal cells or myoblasts, with a p38 MAPK inhibitor. (See, e.g., page 27, lines 30-33).” Ans. 7. Appellants’ argue that the specifically described embodiments of Underhill are restricted to the application of p3 8 MAPK inhibitor to developing embryonic limbs. Underhill, however, does not suggest that the findings made in studying embryonic cells somehow translate to adult satellite cells. In fact, Underhill suggests the opposite, stating that satellite cells are important in “a program that differs from the embryonic myogenic program” (pg.5, lines 10-11; emphasis added). 8 Appeal 2016-005788 Application 13/440,534 App. Br. 5. Notwithstanding this argument, Underhill describes the administration of an inhibitor of the p38 mitogen associated protein kinase (MAPK) systemically to adults with muscle atrophy. FF1,2. Thus, Underhill describes administration to muscle tissue and therefore also to muscle satellite cells. We further agree with the Examiner that the age of 50 years recited in the preamble of the claim appears arbitrary, and is reasonably disclosed by Underhill. According to the Specification, page 16, Aged. As used herein, the term aged refers to the effects or the characteristics of increasing age, particularly with respect to the diminished ability of somatic tissues to regenerate in response to damage, disease, and normal use. One measure of aging, therefore, is evidenced by the intrinsic lack of ability of somatic stem cells to regenerate tissues. Alternatively, aging may be defined in terms of general physiological characteristics. The rate of aging is very species specific, where a human may be aged at about 50 years; and a rodent at about 2 years. In general terms, a natural progressive decline in body systems starts in early adulthood, but it becomes most evident several decades later. One arbitrary way to define old age more precisely in humans is to say that it begins at conventional retirement age, around about 60, around about 65 years of age. Another definition sets parameters for aging coincident with the loss of reproductive ability, which is around about age 45, more usually around about 50 in humans, but will, however, vary with the individual. Furthermore, “Underhill teaches the method can be used to regenerate muscle in a variety of subjects such as fetuses, newborns, children, and adults. (Page 27, lines 26-29). More particularly, Underhill teaches the method can be used to treat late-adult onset Welander distal myopathy and 9 Appeal 2016-005788 Application 13/440,534 repair or replace, i.e., regenerate, muscle tissue (Pages 27-29).” Ans. 3. Because the disclosure of adults in Underhill reasonably includes 50 year old adults, the obviousness rejection is affirmed for the reason of record. Appellants provide no evidence that “adults” would not have been understood by those of ordinary skill in the art to include 50 year old adults. See also FF 1,2. Appellants present similar arguments for rejection 2 as for rejection 1. Brief 8. For rejection 2, Cosgrove is additionally relied upon by the Examiner for the disclosure that hydrogels “are largely resistant to nonspecific cell adhesion mediated by protein adsorption and allow for experimentally determined presentation of ligands, through either covalent or non- covalent (e.g., streptavidin-biotin) binding chemistries, to facilitate cell adhesion through specific protein modifications.’’(Page 191). Cosgrove also teaches that “of particular interest for the in vitro maintenance of satellite cells are the widely-used poly(ethyleneglycol) (PEG)-based hydrogels, which have both tunable matrix stiffness and controlled ligand tethering for inducing receptor activation and cell adhesion.” (Page 191). Final Act. 4. We did not find Appellants’ arguments for rejection 1 convincing. Rejection 2 is affirmed for the reasons of record. CONCLUSION OF LAW The cited references support the Examiner’s obviousness rejections, which are affirmed for the reasons of record. All pending, rejected claims fall. AFFIRMED 10 Copy with citationCopy as parenthetical citation