DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments and/or Claims
The amendment and Applicant's arguments, filed 24 June 2025, have been entered in full. Claims 6-11 are withdrawn from consideration as being drawn to a non-elected invention. Claims 5 and 12 are canceled. Claims 1-3 are amended. Claims 1-4 are under examination.
Withdrawn Objections And/Or Rejections
The rejection to claims 1 and 2 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AlA), second paragraph, as set forth at pages 3-5 of the previous Office Action (26 March 2025), is withdrawn in view of the amendment (24 June 2025).
The objection to claims 3 and 12, as set forth at page 11 of the previous Office Action (26 March 2025), is withdrawn in view of the amendment (24 June 2025).
Claim Rejections-35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4 remain rejected under 35 U.S.C. 103 as being unpatentable over Naumer et al. (Journal of Virology Volume 86 Number 23, p. 13038-13048, December 2012) in view of Boulikas (US 2003/0072794; published 17 April 2003) and Tsien et al. (US 6150176; published 21 November 2000).
The basis for this rejection is set forth at pages 6-11 of the previous Office Action (26 March 2025).
APPLICANT’S ARGUMENTS
Applicant discusses the pending rejection. Applicant argues that claim 1 recites that the engineered AAP comprises a deleted T/S rich region (T/S) of an AAP1 protein or AAP2 protein, or a corresponding T/S rich region in an AAP protein in any of AAV serotypes 3-5, 7-9, or comprises a proline rich region of an AAP, wherein the AAP comprises from N-terminal to C-terminal components A, proline rich region, B, C. Applicant argues that deletion of the T/S rich region from the engineered AAP or an engineered AAP comprising, from N-terminal to C-terminal components A, proline rich region, B, C is not disclosed, suggested or otherwise taught by the combination of references.
Applicant argues that the references fail to provide any rationale for replacing the T/S rich region with other domains. Applicant argues that Naumer, at most, states a portion of the five S/T-motifs can be mutated at two S/T regions without affecting assembly. Applicant argues that Naumer provides no teaching or disclosure of an AAP with deletion of one or more S/T motifs, deletion of the S/T rich region, nor performance of an engineered AAP protein with components A, B and C as claimed. Applicant argues that neither Boulikas nor Tsien provide any further teaching for deletion of the T/S rich region.
Applicant argues that Naumer is said to teach that mutation of conserved amino acids of the proline-rich region had no impairment in the ability to support assembly. Applicant argues that using the reasoning of the Office Action regarding motivation of one of ordinary skill in the art reading the teachings of Naumer, namely that the lack of function would motivate one to delete the T/S region, one of ordinary skill in the art would conclude from a reading of Naumer that there would have been no reason to retain the proline rich region.
Applicant maintains that the present specification teaches the retention of the proline rich region contributed to capsid assembly and serotype specificity and that PRR may contribute as a linker to separate the T/S rich region from the HR and CC domain. Applicant maintains that Naumer fails to teach, disclose or suggest retention of the PRR rich region, particularly when a T/S rich region is present, failing to provide any reasonable expectation of success in arriving at the claimed engineered AAP. Additionally, there is no predictability in replacing the T/S rich regions with other domains or linkers to arrive at the engineered AAPs claimed with a reasonable expectation of success.
Applicant argues that Tsien and Boulikas fail to cure the deficient teachings of Naumer to arrive that the claimed engineered AAP. Applicant argues that the references fail to supply, teach or disclose retaining PRR or deleting the T/S rich regions in an engineered AAP comprising components A, B and C. Applicant states that the Federal Circuit notes, "[b]oth the suggestion and the expectation of success must be founded in the prior art, not in applicant's disclosure." In re Dow Chem. Co., 837 F.2d 469, 473 (Fed. Cir. 1988).
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. In response to Applicant’s arguments that deletion of the T/S rich region from an engineered AAP or an engineered AAP comprising, from N-terminal to C-terminal components A, proline rich region, B, C is not disclosed;
The Examiner notes that amended Claim 1 does not solely read on an assembly activating protein (AAP) wherein the T/S region of an AAP is deleted. Claim 1 encompasses an AAP wherein the T/S region of an AAP is deleted OR an AAP comprising a proline rich region (PRR).
Naumer teaches the amino acid sequences of AAPs from AAV serotypes 1 to 13. Naumer teaches instant SEQ ID NO:1. The teachings of Naumer read on an AAP comprising an A component wherein the A component comprises an N-terminal domain comprising an HR domain and CC domain and having the amino acid sequence comprising SEQ ID NO:1 and the proline rich region (PRR). This also applies to claim 3.
Instant claim 2 solely reads on an AAP comprising an A component wherein the A component comprises an N-terminal domain comprising an HR domain and CC domain and having the amino acid sequence comprising SEQ ID NO:1 and wherein the T/S region of an AAP is deleted.
2. In response to Applicant’s arguments that Naumer fails to provide any rationale for replacing the T/S rich region with other domains, no teaching or disclosure of an AAP with deletion of one or more T/S motifs and/or deletion of the T/S rich region;
The Examiner notes that the instant claims do not recite replacing the T/S motif with other domains. The claims recite wherein the T/S motifs are deleted (specifically claim 2).
Naumer mutates two of the S/T rich areas and states that the mutant constructs were not impaired with supporting VP3 capsid assembly. Naumer clearly states that the five S/T motifs have redundant functions and seem not to be a consequence of the superimposed VP protein sequence.
One skilled in the art would know/understand that “redundant functions and seem not to be a consequence” means that the motifs providing said function are not needed and/or there are other motifs that perform the same function.
3. In response to Applicant’s argument that Naumer fails to teach the performance of an engineered AAP protein with components A, B and C, and that neither Boulikas nor Tsien provide any further teaching for deletion of the T/S rich region;
The Examiner notes that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Naumer et al. teach constructs wherein the T/S motifs are mutated had no impairment in the ability to support VP3 capsid assembly. Naumer et al. teach an engineered assembly activating protein (AAP) comprising an A component wherein the A component comprises an N-terminal domain comprising an HR domain and CC domain and having the amino acid sequence comprising SEQ ID NO:1 wherein the PRR is retained and wherein the T/S motif can be deleted.
Tsien et al. teach the B component. Tsien et al. teach a sequence (SEQ ID NO:3) that is 100% identical to instant SEQ ID NO:2. Boulikas et al. teach the C component. Boulikas et al teach an NLS/NoLS sequence (SEQ ID NO:116) that is 100% identical to instant SEQ ID NO:13.
4. In response to Applicant’s argument that using the reasoning of the Office Action regarding motivation of one of ordinary skill in the art reading the teachings of Naumer, namely that the lack of function would motivate one to delete the T/S region, one of ordinary skill in the art would conclude from a reading of Naumer that there would have been no reason to retain the proline rich region and that Naumer fails to teach, disclose or suggest retention of the PRR rich region;
The Examiner notes Naumer teaches amino acids of the proline-rich region were mutated to histidines and that the mutant constructs were not impaired in supporting VP3 capsid assembly. However, unlike the T/S region, Naumer never states that the proline-rich region has redundant functions and seems not to be a consequence of the superimposed VP protein sequence. Thus, there would be no reason to delete this region.
Further, MPEP 2144 IV teaches: The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by Applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Linter, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972).
5. In response to Applicant’s arguments that there is no predictability in replacing the T/S rich regions with other domains or linkers to arrive at the engineered AAPs claimed with a reasonable expectation of success; that the references fail to supply, teach or disclose retaining PRR or deleting the T/S rich regions in an engineered AAP comprising components A, B and C and that the Federal Circuit notes, "[b]oth the suggestion and the expectation of success must be founded in the prior art, not in applicant's disclosure." In re Dow Chem. Co., 837 F.2d 469, 473 (Fed. Cir. 1988);
The Examiner notes that obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O' Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).
Obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In the instant case, Naumer teaches an engineered assembly activating protein (AAP) comprising an A component wherein the A component comprises an N-terminal domain comprising an HR domain and CC domain and having the amino acid sequence comprising SEQ ID NO:1 wherein the PRR is retained and wherein the T/S motif can be deleted.
Tsien et al. teach the B component. Tsien et al. teach a sequence (SEQ ID NO:3) that is 100% identical to instant SEQ ID NO:2. Boulikas et al. teach the C component. Boulikas et al teach an NLS/NoLS sequence (SEQ ID NO:116) that is 100% identical to instant SEQ ID NO:13.
The sequence taught by Tsien is a linker green fluorescent protein (GFP), which would allow the components taught by Naumer be linked to the NLS/NoLS sequence. GFP also allows the protein to be visualized via the green fluorescent activity. NLS/NoLS are sequences are essential for the proper transport of proteins to the nucleus.
The scientific reasoning and evidence as a whole indicates that the objection should be maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ELIZABETH C. KEMMERER/ Primary Examiner, Art Unit 1674
/R.M.D/Examiner, Art Unit 1647 9/11/2025
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