CureVac GmbHDownload PDFPatent Trials and Appeals BoardApr 9, 202014487425 - (D) (P.T.A.B. Apr. 9, 2020) 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. 14/487,425 09/16/2014 Florian VON DER MÜLBE CRVC.P0003US.D1 1723 108197 7590 04/09/2020 Parker Highlander PLLC 1120 South Capital of Texas Highway Bldg. 1, Suite 200 Austin, TX 78746 EXAMINER WOITACH, JOSEPH T ART UNIT PAPER NUMBER 1631 NOTIFICATION DATE DELIVERY MODE 04/09/2020 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@phiplaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte FLORIAN VON DER MÜLBE, INGMAR HOERR, and STEVE PASCOLO Appeal 2019-004883 Application 14/487,425 Technology Center 1600 BEFORE DEBORAH KATZ, JOHN E. SCHNEIDER, and MICHAEL A VALEK, Administrative Patent Judges. SCHNEIDER, Administrative Patent Judge. DECISION ON APPEAL STATEMENT OF THE CASE Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 29–33 and 35–45. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42(a). Appellant identifies the real party in interest as CureVac AG. Appeal Br. 3. Appeal 2019-004883 Application 14/487,425 2 CLAIMED SUBJECT MATTER The claims are directed to stabilizing mRNA for use in a pharmaceutical composition. Spec.¶ 2. Claim 29, reproduced below, is illustrative of the claimed subject matter: 29. A method for producing a stabilized mRNA comprising synthesizing an mRNA molecule encoding a native polypeptide sequence, wherein the mRNA encoding the polypeptide comprises a nucleic acid sequence that has an increased Guanine/Cytosine (G/C) content relative to the native nucleic acid sequence encoding the polypeptide, said relative G/C content being increased by at least 7 percentage points compared to native nucleic acid sequence encoding the polypeptide, to thereby produce a stabilized mRNA molecule, wherein said increase in relative G/C content results in the elimination of at least one destabilizing sequence element (DSE), wherein a polypeptide encoded by said stabilized mRNA molecule exhibits enhanced translational efficiency compared to a polypeptide encoded from the native nucleic acid sequence. REFERENCES The prior art relied upon by the Examiner is: Name Reference Date Felgner, et al. (Felgner) US 5,580,859 Dec. 3, 1996 Neeper, et al. (Neeper) WO 01/14416 A2 Mar. 1, 2001 Seldon, et al. (Seldon) WO 02/064799 A2 Aug. 22, 2002 Fujimoto EP 0175960 A1 Apr. 2, 1986 GenBank, Accession No. AF125673, Human papillomavirus type 16, isolate 16W12E, complete genome, found at http://www.ncbi.nlm.nih.gov/nuccore/AF125673.1, last accessed Oct. 6, 2015 Appeal 2019-004883 Application 14/487,425 3 REJECTIONS The Examiner has rejected the pending claims as follows: Claims 29–33 and 35–45 have been rejected under 35 U.S.C. § 112, second paragraph, and indefinite. Claims 29–33 and 35–45 have been rejected under 35 U.S.C. § 112, first paragraph for failure to comply with the written description requirement. Claims 29–33, 35–42, and 44–45 have been rejected udner35 U.S.C. § 103(a) as unpatentable over Neeper in view of Felgner, Seldon, GenBank and Fujimoto OPINION Indefiniteness The issue with respect to this rejection is whether the Examiner has correctly determined that the rejected claims fail to particularly point out and distinctly claims the subject matter the inventors regard as their invention. The Examiner finds that the term “enhanced translational efficiency” is indefinite in that the Specification teaches that stability and efficiency are determined in a particular context and is relative to the specific conditions in which it is assessed. Final Act. 3. The Examiner finds that the claims do not recite how stability and efficiency are to be assessed. Id. Appellant contends that the term “stabilized” is well known in the art. Appeal Br. 4. Appellant contends that the term means “to maintain at a given or unfluctuating level or quantity.” Id. Appellant contends that one skilled in the art would apply this definition to the term and it is used in the Specification and claims. Id. at 4–5. Appeal 2019-004883 Application 14/487,425 4 With respect to the term “enhanced,” Appellant contends that [a] skilled artisan would immediately recognize[] that relative to a RNA an enhanced translational efficiency would merely mean that more protein translated or expressed from the RNA. Appellants note that the claims provide a basis for measuring "enhanced" expression (or ehanced [sic] translational efficiency), namely, as compared to an unmodified mRNA sequence. This is believed to provide an adequate reference point so that the relative aspect of "enhanced" is clear. Id. at 5. Claims are in compliance with 35 U.S.C. § 112, second paragraph, if “the claims, read in light of the specification, reasonably apprise those skilled in the art and are as precise as the subject matter permits.” Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1385 (Fed. Cir. 1986). “[T]he definiteness of the language employed must be analyzed—not in a vacuum, but always in light of the teachings of the prior art and of the particular application disclosure as it would be interpreted by one possessing the ordinary level of skill in the pertinent art.” In re Moore, 439 F.2d 1232, 1235 (CCPA 1971). We have considered the arguments advanced by the Examiner and Appellant and conclude that Appellant as the better position. The present claims, when read in light of the Specification and the state of the art, clearly define the subject matter the inventor regards as his invention. The Examiner contends that stability and enhancement must be determined relative to a specific context and that neither the claims nor the specification give any context for determining those limitations. Ans. 5. The Examiner maintains that, absent such a context, the terms are indefinite. Id. Appeal 2019-004883 Application 14/487,425 5 We are not persuaded. As Appellant points out, the comparison is relative to the unmodified mRNA sequence. Reply Br. 5. This is clear from the language of the claims themselves as well as from the Specification. See Resp. Non-complaint Brief 2; Spec. ¶33. The other conditions are irrelevant as long as they are the same for both sets of molecules. Reply Br. 5. We conclude that the Examiner has not established that the pending claims are indefinite. Written Description The issue with respect to this rejection is whether the Examiner has established that the present claims fail to comply with the written description requirement. The Examiner finds that there is no support for the term “enhanced” as it is used in connection with translation efficiency. Final Act. 6. The Examiner finds that the Specification refers to codon optimization for translation efficiency and the Examiner finds that this does not equate to enhanced translation efficiency. Id. The Examiner concludes “[g]iven the lack of specific guidance and lack of evidence that a change in G/C content inherently enhances translation, the embodiment of enhanced translational efficiency [is] found to be new matter.” Id. at 7. Appellant contends that the Specification teaches that codon optimization results in improved translational efficiency and that the use of the term “enhanced” is synonymous with the term improved. Appeal Br. 6 (Citing Spec. ¶ 94). “In order to satisfy the written description requirement, the disclosure as originally filed does not have to provide in haec verba support for the Appeal 2019-004883 Application 14/487,425 6 claimed subject matter at issue.” Purdue Pharma L.P. v. Faulding, Inc., 230 F.3d 1320, 1323 (Fed. Cir. 2000). We have considered the positions advanced by the Examiner and Appellant and again conclude that Appellant has the better position. While we agree with the Examiner that the term “enhanced” does not literally appear in the Specification, the Specification does refer to improved translational efficiency. Spec. ¶ 94. We agree with Appellant that when read in context of the Specification, one skilled in the art would equate improved with enhanced. Appeal Br. 6. We conclude that the Examiner has not established that the term “enhanced” is not supported by the Specification. Obviousness The issue with respect to this rejection is whether the Examiner has demonstrated by a preponderance of the evidence that the subject matter of the pending claims would have been obvious over Neeper combined with Felgner, Seldon, GenBank and Fujimoto. The Examiner finds that Neeper teaches DNA vaccines papillomavirus genes which have been codon optimized for expression in a human cellular environment. Final Act. 15. The Examiner finds that one sequence encoding for a HPV exhibits a 23.6 % increase in G/C content relative to the wild type. Id. The Examiner also finds that each sequence reported inn Neeper has a maximum G/C content. Id. The Examiner finds that Neeper teaches that the codon optimization results inn improved expression yields relative to the wild-type sequence. Id. at 15–16. The Examiner cites to Fujimoto to show the codons that encode for the different amino acids. Id. at 16. The Examiner finds Seldon teaches increasing yield by replacing infrequently used codons with more frequently Appeal 2019-004883 Application 14/487,425 7 used codons, which would include codons containing both G and C. Id. The Examiner finds that Seldon teaches that “the starting point for optimization of an mRNA may be a coding sequence with 100% common codons or a sequence that contains a mixture of common and noncommon codons.” Id. With respect to Felgner, the Examiner finds that Felgner teaches pharmaceutical compositions comprising an aqueous carrier and a modified mRNA that encodes for a polypeptide. Id. The Examiner finds that Felgner teaches modifying the mRNA to provide a greater half-life. Id. The Examiner finds that Felgner does not teach increasing G/C content to greater than 7% relative to the wild-type mRNA. Id. at 17. The Examiner finds that combining the teachings of Neeper and Felgner would result in a modified mRNA having greater than 7% G/C content. The Examiner concludes: One would have been motivated to make such a modification in order to receive the expected benefit of providing mRNA encoding tumor antigens for a specific type of cancer as taught by Neeper et al. Furthermore, one would have made such a modification to provide mRNA with maximum G/C content due to the replacement of rare codons with common codons of highly expressed genes (codons recognized by abundant cellular tRNA), which would allow for improved expression of the HPV antigens and more specifically, Seldon et al teach the preferred human codon usage, which has maximal G/C content for use and expression in a human cell. Id. at 18. Appellant contends that there is no motivation to combine the references. Appeal Br. 7. In support of this contention Appellant points to our decision in Appeal 2016-005808 where we found a lack of motivation to combined Felgner and Neeper. Id. at 8–11. Appellant contends that the Appeal 2019-004883 Application 14/487,425 8 same logic applied to the combination of references in the present appeal. Id. Appellant also contends that none of the references teach or suggest modifying the mRNA to increase the G/C content to over 7% relative to the wild-type. Appeal Br. 14. Appellant contends that the codon optimization taught by Neeper does not necessarily result in a G/C content of over 7% greater than the wild-type. Id. A proper § 103 analysis requires “a searching comparison of the claimed invention—including all its limitations—with the teaching of the prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995). A party must, therefore, meet a high standard in order to rely on inherency to establish the existence of a claim limitation in the prior art in an obviousness analysis––the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art. Par Pharmaceuticals Inc., v. TWI Pharmaceuticals, Inc., 773 F3d 1186, 1195–96 (Fed. Cir. 2014). Having considered the arguments presented by both the Examiner and Appellant and the evidence of record, we conclude that the Examiner has failed to establish that the subject matter of the present claims would have been obvious. While we agree with the Examiner that the art generally teaches codon optimization, the art does not teach or suggest increasing the G/C content by at least 7 percentage points over the native nucleic acid sequence. The Examiner’s reliance on Neeper for this limitation is misplaced. While Neeper discloses an example where the G/C level exceeded 7%, as Appellant points out, the codon optimization method of Neeper does not always lead to a G/C content of over 7%. Appeal Br. 13–15. Appellant has Appeal 2019-004883 Application 14/487,425 9 submitted evidence in the form of a declaration of Dr. Byrd2 showing that the optimization technique of Neeper can result in a G/C content of less than 7%. Id. (Citing Byrd Decl.) The Declaration of Dr. Byrd demonstrates that the optimization technique of Neeper does not inevitably lead to a G/C content of over 7%. The Examiner points to nothing in the remaining references that remedies the deficiencies in Neeper. While Seldon teaches codon optimization, which may include increased G/C content, we find nothing in Seldon which teaches or suggests increasing G/C content to greater than 7% relative to the native sequence. See Sheldon 26–27. We conclude that the Examiner has not established by a preponderance of the evidence that the subject matter of the present claims would have been obvious over Neeper combined with Felgner, Seldon, GenBank and Fujimoto. CONCLUSION The Examiner’s rejections are reversed. More specifically, The rejection under 35 U.S.C. §112, second paragraph for indefiniteness is reversed. The rejection under 35 U.S.C. § 112, first paragraph for failure to comply with the written description requirement is reversed. The rejection under 35 U.S.C. §103(a) as unpatentable over Neeper combined with Felgner, Seldon, GenBank and Fujimoto is reversed. 2 Declaration Under 37 C.F.R. § 1.132, originally filed in Application 10/729,830 Dec. 15, 2014. Appeal 2019-004883 Application 14/487,425 10 DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 29–33, 35–45 112 Indefiniteness 29–33, 35–45 29–33, 35–45 112 Written Description 29–33, 35–45 29–33, 35–45 103(a) Neeper, Felgner, Seldon, GenBank, Fujimoto 29–33, 35–45 Overall Outcome 29–33, 35–45 REVERSED Copy with citationCopy as parenthetical citation