Ex Parte Nusse et alDownload PDFPatent Trial and Appeal BoardOct 21, 201312041538 (P.T.A.B. Oct. 21, 2013) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte ROELAND NUSSE, M. YASHAR KALANI, and SAMUEL CHESHIER __________ Appeal 2012-002996 Application 12/041,538 Technology Center 1600 __________ Before LORA M. GREEN, JEFFREY N. FREDMAN, and ERICA A. FRANKLIN, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35 U.S.C. § 134 involving claims to a method for in vitro expansion of mammalian central nervous system (CNS) neural stem cells. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 Appellants identify the Real Party in Interest as the Board of Trustees of the Leland Stanford Junior University (see App. Br. 1). Appeal 2012-002996 Application 12/041,538 2 Statement of the Case Background “Methods are provided for the expansion of neural progenitor or stem cells in vitro, whereby the cells retain their pluripotential phenotype after expansion. The cells are cultured in the presence of a wnt activating agent, e.g. a wnt polypeptide. The alteration in wnt signaling provides for cultures that maintain an undifferentiated phenotype in vitro” (Spec. 2 ¶ 07). The Claims Claims 1, 4, 5, and 7-13 are on appeal. Claim 1 is representative and reads as follows: 1. A method for in vitro expansion of mammalian central nervous system (CNS) neural stem cells, the method comprising: culturing CNS neural stem cells in medium comprising one or more added wnt polypeptides, wherein said CNS cells can self-renew and can differentiate into neurons, astrocytes and oligodendrocytes; wherein the number of CNS neural stem cells is expanded at least 2.5-fold over a control culture lacking said added wnt polypeptides. The issue The Examiner rejected claims 1, 4, 5, and 7-13 under 35 U.S.C. § 103(a) as obvious over McMahon2 (Ans. 5-8). The Examiner finds that McMahon teaches “methods for enriching neural precursor cells that maintain a stem cell phenotype in the presence of Wnt polypeptides (page 1, lines 33-35), and specifically teaches contacting human or porcine neural precursor cells derived from fetal tissue with Wnt- 3a (page 2, lines 5-8)” (Ans. 5). The Examiner finds that McMahon teaches 2 McMahon et al., WO 99/57248 A1, published Nov. 11, 1999. Appeal 2012-002996 Application 12/041,538 3 “their method induces proliferation of neural precursor cells that are able to ‘differentiate into glial cells, schwann cells ... parasympathetic neurons, as well as peptidergic and serotonergic neurons’ (page 17, lines 24-29)” (Ans. 6). The Examiner finds that “since the McMahon reference discloses a method comprising substantially identical materials and method steps, any increase in the yield of CNS neural stem cells would be substantially identical also” (Ans. 7). The Examiner finds that while “the McMahon reference does not teach optimization of the method to produce a yield of 2.5-fold, such optimization would have been achieved through routine experimentation” (Ans. 7-8). The issue with respect to this rejection is: Does the evidence of record support the Examiner’s conclusion that McMahon renders claim 1 obvious? Findings of Fact 1. McMahon teaches “an enriched population of mammalian dorsal neural precursor cells that maintain a stem cell phenotype in the presence of a Wnt polypeptide” (McMahon 1, ll. 33-35). 2. McMahon teaches that: Neural precursor cells selectively proliferate in the presence of the Wnt polypeptide, whereas other precursor cells do not proliferate (or proliferate at a rate lower than that of the dorsal neural precursor cells). Thus, repeated culturing of the population in this manner yields a population of neural precursor cells that is progressively more enriched for dorsal neural precursor cells. (McMahon 2, ll. 25-32). Appeal 2012-002996 Application 12/041,538 4 3. McMahon teaches that “the cells maintain a stem cell phenotype in culture in the presence of a Wnt-3a polypeptide. Such precursor cells cease proliferating and differentiate into hippocampal neurons in the absence of the Wnt-3a polypeptide” (McMahon 5, ll. 14-18). 4. McMahon teaches that: Primary neural progenitor cells are obtained from a mammalian source, e.g., fetal CNS precursor tissue such as developing neural crest tissue, using known methods. Such primary cells are cultured in the presence of a Wnt polypeptide such as Wnt-1 class polypeptide (purified from a natural source or produced recombinantly) in conventional tissue culture medium such as Dulbecco’s Modified Eagles Medium (DMEM) containing fetal calf serum or in serum- free tissue culture medium. (McMahon 7, l. 30 to 8, l. 3). 5. McMahon teaches that “[h]uman heterologous neural progenitor cells may be derived from fetal tissue obtained from elective abortion, or from a post-natal, juvenile or adult organ donor. Autologous neural tissue can be obtained by biopsy, or from patients undergoing neurosurgery in which neural tissue is removed” (McMahon 15, ll. 1-6). 6. McMahon teaches that “[d]issociated cells can be placed into any culture medium capable of supporting cell growth, including MEM, DMEM, RPMI, F-12” (McMahon 15, ll. 23-25). 7. McMahon teaches that the “[c]ells can be grown in suspension or on a fixed substrate, but proliferation of the precursor cells is preferably done in suspension to generate large numbers of cells by formation of ‘neurospheres’” (McMahon 16, ll. 1-4). Appeal 2012-002996 Application 12/041,538 5 8. McMahon teaches that the “tissue culture media is supplemented with a Wnt polypeptide (either by adding a Wnt polypeptide to the culture media or by adding feeder cells producing a Wnt polypeptide) to maintain a stem cell phenotype of the precursor cells and to promote proliferation of the cells” (McMahon 16, l. 34 to 17, l. 4). 9. McMahon teaches that “[d]ifferentiation of the cells can proceed upon the removal of the Wnt polypeptide and/or addition of a composition that promotes differentiation” (McMahon 17, ll. 10-12). 10. McMahon teaches that the “Wnt polypeptide is preferably a Wnt-1 class polypeptide such as Wnt-1, Wnt-2, Wnt-3a, Wnt-7a, and Wnt- 7b” (McMahon 2, ll. 8-10). 11. The Specification teaches that “[v]arious media are commercially available and may be used, including . . . Dulbecco’s Modified Eagle Medium (DMEM), RPMI” (Spec. 9 ¶ 39). 12. The Specification teaches, regarding differentiation conditions, that “[n]eurosphere cells were harvested, and cultured with differentiation medium [Nacetylcsteine, brain-derived neurotrophic factor (10 ng/ml) glial- derived neurotrophic factor (10 ng/ml), EFG and FGF on laminin-coated chamber slides” (Spec. 13 ¶ 57). Principles of Law “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” Id. at 417. Appeal 2012-002996 Application 12/041,538 6 Analysis McMahon teaches that “the cells maintain a stem cell phenotype in culture in the presence of a Wnt-3a polypeptide. Such precursor cells cease proliferating and differentiate into hippocampal neurons in the absence of the Wnt-3a polypeptide” (McMahon 5, ll. 14-18; FF 3). McMahon extensively teaches that mammalian, including human, central nervous system (CNS) neural stem cells may be cultured in vitro in media using the Wnt protein (FF 1-8) and then can differentiate into neurons and other cell types (FF 3, 9). Appellants contend that McMahon “is not issued as a patent in the United States, and therefore, has no presumption of validity” (App. Br. 3). Appellants “submit that the cited document is completely speculative with respect to culture of neuronal stem cells, and further fails to provide sufficient guidelines for one of skill in the art to practice the invention, and thus fails to provide an enabling disclosure” (App. Br. 3). We are not persuaded. “[D]uring patent prosecution, an examiner is entitled to reject claims . . . by a prior art publication or patent without conducting an inquiry into whether or not that prior art reference is enabling. As long as an examiner makes a proper prima facie case . . . by giving adequate notice under § 132, the burden shifts to the applicant to submit rebuttal evidence of nonenablement.” In re Antor Media Corp., 689 F.3d 1282, 1289 (Fed. Cir. 2012). Appellants have not submitted any rebuttal evidence showing that McMahon would not have been enabled, nor have Appellants provided any specific argument or reason to suggest why McMahon would not have Appeal 2012-002996 Application 12/041,538 7 provided sufficient information for the ordinary artisan to practice the invention. Indeed, McMahon specifically teaches that neural cell tissue, obtained from the neural crest using known methods, may be cultured in one of the most common of known culture media, DMEM, with Wnt polypeptides (FF 4). We conclude that the ordinary artisan would have reasonably been enabled to perform the method steps taught by McMahon (FF 1-9). Appellants submit that the teachings of the present application, which, it is noted, provide actual data for the cell phenotype, abundantly demonstrate that culturing neural stem cells with wnt does not lead to selective enrichment for a specific neural cell subtype precursor, but rather provides for proliferation of a multipoint cell that can give rise to a plurality of cell types, including neurons, oligodendrocytes and astrocytes. (App. Br. 3). Appellants further “submit that the cited art fails to teach methods that teach an expansion of neural progenitor cells, as is set forth in the present claims” (App. Br. 4). We are not persuaded. McMahon teaches the use of CNS neural stem cells (FF 1, 5) and McMahon teaches culturing these cells in media with Wnt (FF 4, 8). Indeed, both the Specification and McMahon teach the use of the same media, DMEM and RPMI (FF 6, 11) which both result in the formation of neurospheres (FF 7, 12). McMahon teaches that the CNS neural stem cells have the capacity to differentiate into neurons (FF 5). The Specification demonstrates that such differentiation inherently occurs under particular conditions (FF 12). Appeal 2012-002996 Application 12/041,538 8 Based on this fact pattern, we find that cells removed from the neurospheres produced by culturing neural stem cells with the Wnt protein as taught by both the Specification or by McMahon inherently “can differentiate into neurons, astrocytes and oligodendrocytes” as required by claim 1 (FF 4-6, 11, 12). We also find, that given that both McMahon’s cells and those of the Specification proliferate to form “neurospheres” (FF 7, 12), the Examiner reasonably finds that the 2.5 fold expansion of cells is either inherent or obvious as an optimizable variable (see Ans. 6). These arguments are consistent with the Examiner’s finding that “something which is old does not become patentable upon the discovery of a new unknown effect that is inherently present in the prior art” (Ans. 7). See In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (“Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. . . .Whether the rejection is based on ‘inherency’ under 35 U.S.C. § 102, on ‘prima facie obviousness' under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products.). Appellants have provided no evidence which rebuts the Examiner’s positions, only argument. Appellants “submit that the cited reference fails to teach an effective range of wnt polypeptide concentration for the asserted cultures, fails to teach an effective dose of wnt polypeptide, and further fails to teach how one of skill in the art could determine the effective ranges” (App. Br. 4). Appeal 2012-002996 Application 12/041,538 9 We are not persuaded. There are no limitations in any of Appellants’ claims to specific wnt polypeptide concentrations or specific wnt polypeptide doses. Thus, Appellants’ entire argument is not directed to the claim as written. “[L]imitations are not to be read into the claims from the specification.” In re Van Geuns, 988 F.2d 1181, 1184 (Fed. Cir. 1993). Conclusion of Law The evidence of record supports the Examiner’s conclusion that McMahon renders claim 1 obvious. SUMMARY In summary, we affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as obvious over McMahon. Pursuant to 37 C.F.R. § 41.37(c)(1), we also affirm the rejection of claims 4, 5, and 7-13 as these claims were not argued separately. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED lp Copy with citationCopy as parenthetical citation