Ex Parte Cooke et alDownload PDFPatent Trial and Appeal BoardJan 26, 201813744272 (P.T.A.B. Jan. 26, 2018) 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. 13/744,272 01/17/2013 John P. Cooke STAN-928 5403 77974 7590 01/30/2018 Stanford University Office of Technology Licensing Bozicevic, Field & Francis LLP 201 REDWOOD SHORES PARKWAY SUITE 200 REDWOOD CITY, CA 94065 EXAMINER EPPS -SMITH, JANET L ART UNIT PAPER NUMBER 1633 NOTIFICATION DATE DELIVERY MODE 01/30/2018 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 JOHN P. COOKE, JI EUN LEE, and NAZISH SAYED1 Appeal 2017-003866 Application 13/744,272 Technology Center 1600 Before RICHARD J. SMITH, JOHN E. SCHNEIDER, and DAVID COTTA, Administrative Patent Judges. SCHNEIDER, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims a method for reprograming cells which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. STATEMENT OF THE CASE Certain transcription factors, such as Oct %, Sox2, c-Myc, Klf4, Lin28 and Nanog, are known to induce pluripotency in somatic cells. Spec. 1. Induced pluripotent stem cells (iPSC) can be used to treat disease and in 1 Appellants identify the Real Party in Interest as Board of Trustees of the Leland Stanford Junior University. Br. 1. Appeal 2017-003866 Application 13/744,272 patient-specific regenerative medicine therapies. Id. Current methods used to generate transcription factors involve the use of plasmids of viral vectors to induce overexpression of the reprogramming factors. Id. The drawbacks of this method is that it results in low efficiency and cannot be precisely controlled. Id. In addition, the method increases the risk of incorporation of foreign DNA into the host genome. Id. The Specification describes methods and compositions for efficient generation of induced pluripotent cells or transdifferentiated cells using non integrating methods. Claims 2—10, 13—15, 25, and 26 are on appeal.2 Claim 4 is representative3 and reads as follows: 4. A method of reprogramming a mammalian somatic cell to pluripotency, the method comprising: contacting a population of mammalian somatic cells in vitro with (a) an effective dose of an innate immune response activator wherein the innate immune response activator is a Toll-like receptor (TLR) agonist; and (b) a cocktail of non integrating reprogramming factors; for a period of time sufficient to reprogram or transdifferentiate said mammalian somatic cells to desired cell type of interest. 2 The rejection of claim 11 is withdrawn. (Ans. 2.) 3 Although Appellants provide a grouping of claims (Br. 3, Groups I—V), Appellants provide common arguments as to all claims on appeal (Br. 3—7). Appellants also refer in the Brief to claim 20 being on appeal, but claim 20 was cancelled pursuant to an amendment dated Sept. 23, 2015. 2 Appeal 2017-003866 Application 13/744,272 The claims have been rejected under 35 U.S.C. § 103(a) as unpatentable over Jaenisch4 in view of Aubin5 in further view of Howard6 and Gantier.7 DISCUSSION Issue The issue with respect to the rejection is whether a preponderance of the evidence supports the Examiner’s conclusion that the claims would have been obvious over Jaenisch combined with Aubin, Howard, and Gantier. The Examiner finds that Jaenisch teaches a method for reprogramming somatic cells by contacting somatic cells with at least one reprogramming agent where the reprograming agent can be a nucleotide or a peptide. Ans. 5—6. The Examiner finds that the reprogramming agent can be microRNA. Ans. 7. The Examiner finds that Jaenisch does not teach that the reprogramming agent can be an innate immune response activator such as a TLR agonist. Ans. 9. The Examiner finds that Aubin teaches that certain dsRNA are agonists of TLRs and are innate immune response activators. Ans. 9. The Examiner finds that Howard teaches that microRNAs act as reprogramming agents. Ans. 11. The Examiner finds that Gantier teaches that microRNAs are involved in both innate immunity and transduction signaling by Toll-like 4 Jaenisch et al., US 2011/0076678 Al, published Mar. 31, 2011 (“Jaenisch”). 5 Aubin et al., US 2011/0076296 Al, published Mar. 31, 2011 (“Aubin”). 6 Howard et al., MicroRNAs regulating cellpluripotency and vascular differentiation, 55 Vascular Pharm. 69 (2011) (“Howard”). 7 Gantier et al., Fine-tuning of the innate immune response by microRNAs, 85 Immunol. Cell Biol. 458 (2007) (“Gantier”). 3 Appeal 2017-003866 Application 13/744,272 receptors. Id. The Examiner concludes that it would have been obvious to one skilled in the art at the time the invention was made to use the TLR agonists of Aubin as one of the reprogramming agents in Jaenisch. Ans. 11— 12. Appellants contend that the art does not teach or suggest the role of innate immunity in cell reprograming, therefore, one skilled in the art would not be motivated to combine reprogramming factors with TLR agonists. Br. 4. Appellants contend that the dsRNA in Jaenisch trigger sequence specific degradation thus excludes TLR agonists. Id. at 5. Appellants argue that Jaenisch teaches the use of encoded peptides whereas the present claims are directed to permeant peptides and that the Specification demonstrates that the two act differently. Id. Appellants contend that the references do not teach the need to use innate immunity activation to improve the action of non-integrating reprogramming factors. Id. at 6. Findings of Fact We adopt the Examiner’s findings as our own, including with regard to the scope and content of, and motivation to modify or combine, the prior art. The following findings are included for emphasis and reference purposes. ELI. Jaenisch discloses a method of reprogramming one or more somatic cells to a less differentiated state by treating the cells with an agent. Jaenisch | 8. FF2. One of the reprogramming factors that can be used in the method of Jaenisch is microRNA. Jaenisch ]f]f 15—16. FF3. Other reprogramming agents used in Jaenisch are transcription factors such as Oct4, Sox2, Klf4, and c-Myc. Jaenisch 123. 4 Appeal 2017-003866 Application 13/744,272 FF4. Jaenisch teaches: The treatment can be, by way of non-limiting example, contacting the cells with a known or candidate reprogramming agent (e.g., an agent which alters the chromatin structure of the cell, an agent which decreases DNA methylation, an agent which decreases histone acetylation) transfecting the cells with a polynucleotide encoding a reprogramming agent, and/or culturing the cells under conditions that differ from standard culture conditions in which such cells are typically maintained. For example, the temperature or pH could be varied. Multiple known or candidate reprogramming agents may be used concurrently/simultaneously or sequentially. In another embodiment, methods of the invention may further include repeating the steps of treating the cells with an agent or factor. The agent used in the repeating treatment may be the same as, or different from, the one used during the first treatment. Reprogramming agents of the invention can be polynucleotides, polypeptides, small molecules, etc. Jaenisch 176. FF5. Aubin discloses dsRNAs which act as TLR agonists. Aubin | 6. FF6. The dsRNA of Aubin may have at least 18 or 20 nucleotides. Id. FF7. Howard discloses microRNAs which act as reprogramming factors. Howard 7 0—71. FF8. Gantier teaches that microRNAs are involved in innate immune response and act as TLR agonists. Gantier Abstract. FF9. Gantier teaches that microRNAs are part of a class of small RNAs which have between 19 and 25 nucleotides. Gantier 458 Principles of Law [T]he examiner bears the initial burden, on review of the prior art or on any other ground, of presenting a prima facie case of 5 Appeal 2017-003866 Application 13/744,272 unpatentability. If that burden is met, the burden of coming forward with evidence or argument shifts to the applicant. After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument. In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Inti Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the answer depends on “whether the improvement is more than the predictable use of prior art elements according to their established functions.” Id. at 417. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose. . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980) (citations omitted). Analysis Claim 4 is representative of the rejected claims and is recited above. We conclude that a preponderance of the evidence supports the Examiner’s conclusion that claim 4 would have been obvious to one of ordinary skill in the art at the time the invention was made. Jaenisch teaches a method for reprogramming somatic cells to a pluripotent state by treating the cells with one or more reprogramming agents. FF 1. The 6 Appeal 2017-003866 Application 13/744,272 reprogramming agents can be nucleotides such as microRNAs or they can be peptides such as Oct4, Sox2, Klf4, and c-Myc. FF 2—\. Aubin discloses that dsRNAs act as TLR agonists. The dsRNA used in Aubin include small RNAs having 18 or 20 nucleotides. FF5 & 9. Howard and Gantier teach that microRNAs act as reprogramming agents. FF 6—7. Gantier also teaches that microRNAs are innate immunity response activators and act as TLR agonists. FF 8. We agree with the Examiner that one skilled in the art would have been motivated to use a TLR agonist as one of the reprogramming agents in the method of Jaenisch as the TLR agonists can also act as reprogramming agents. Ans. 14. We have considered Appellants’ arguments and find them unpersuasive. The motivation to combine the references stems from the fact that both TLR agonists and the transcription factors are known reprogramming agents. It is obvious to combine known elements having equivalent properties for the same purpose absent evidence of unexpected results. KSR, 550 U.S. at 416. Here, Appellants have not presented any evidence that the combination yields unexpected results. With respect to Appellants’ argument that the art does not reflect an understanding of the role innate immunity plays in reprogramming, Br. 4, we are unpersuaded. As the Examiner points out, Gantier discloses that microRNA is a TLR agonist and plays a role in both cellular differentiation and innate immunity. Ans. 12—13. Appellants contend that Jaenisch does not teach the use of TLR agonists as a reprogramming agent or its use in combination with a non integrating reprogramming agent. Br. 4. Again, we are unpersuaded. Jaenisch teaches the use of one or more reprogramming agents including 7 Appeal 2017-003866 Application 13/744,272 non-integrating agents such as Oct4. FF 3^4. Aubin teaches that dsRNAs are TLR agonists and Howard and Gantier teach the role of microRNAs a reprogramming agents. FF 6—8. As discussed above, the combined teachings of the references would lead one skilled in the art to the claimed method. Appellants next argue that Jaenisch teaches the use of encoded peptides and not exogenous peptides. Br. 5. Appellants contend that the evidence of record shows that exogenous peptides and encoded peptides do not have the same functionality. Id. We remain unpersuaded. Jaenisch teaches the use of peptides themselves as reprogramming agents not just encoded peptides. FF 4; Jaenisch claims 193, 195, and 196. CONCLUSION We find that a preponderance of the evidence supports the Examiner’s conclusion that claim 4 would have been obvious over Jaenisch combined with Aubin, Howard, and Gantier. Claims 2, 3, 5—10, 13—15, 25, and 26 have not been argued separately and therefore fall with claim 4. 37 C.F.R. § 41.37(c)(l)(iv). SUMMARY We affirm the rejection under 35 U.S.C. § 103(a). TIME PERIOD FOR RESPONSE 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 8 Copy with citationCopy as parenthetical citation