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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/04/2026 has been entered.
Priority
This application claims the benefit of priority to Patent Application PCT/JP2019/027717. Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/JP2019/027717, filed on 07/12/2019.
Information Disclosure Statement
The Information Disclosure Statements filed 03/29/2022, 06/10/2022, and 06/09/2023 have been considered by the Examiner.
Status of Claims
Claims 1 and 7-12 are under examination.
Claims 2-6 are cancelled.
Claim Objections
Objection to claim 9 has been withdrawn in view of the applicants arguments filed 03/04/2026, see pages 4-5.
Claim Rejections - 35 USC § 102
Rejection to claims 1, 5-6, and 9 under 35 U.S.C. 102(a)(1) as being unpatentable by Russel et al (US 6,156,303) have been withdrawn in view of the applicant’s amendments filed 08/06/2025.
Rejection to claims 1, 4, 7, 8, 9, 11, and 12 under 35 U.S.C. 102(a)(1) as being unpatentable by Gao et al (US 7,282,199 B2) have been withdrawn in view of the applicant’s amendments filed 08/06/2025.
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.
Rejection to claims 2-3 and 10 under 35 U.S.C. 103 as being unpatentable over Gao et al (US 7,282,199 B2) as applied to claims 1, 4, 7, 8, 9 11, and 12 and further in view of Asokan (WO 2017/ 058892 A2) have been withdrawn in view of the applicant’s amendments filed 08/06/2025.
Rejection maintained (claim mapping updated for amino acid position correction):
Claims 1 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Russel et al (US 6,156,303) in view of Asokan (WO 2017/ 058892 A2).
Regarding claims 1 and 9, Russel et al teaches an adeno-associated viral vector (AAV) comprising a capsid protein sequence which has at least one of serine at position 472, serine at position 587 and asparagine at position 706 in the amino acid, which is sequence 6 (column 51- 53). Sequence 6 of Russel reads on SEQ ID: 3 of the current application. The peptide portion of an AAV polypeptide is exemplified by amino acids 142 to 147 of AAV3B VP1 (SEQ ID NO: 6; FIG. 2), since this six amino acid Sequence is unique to AAV3B as compared to AAV2, AAV3A and AAV6 (column 20, lines 7-9). Since such epitopes are unique to AAV3B an antibody that specifically binds to an AAV3B polypeptide, but not to the corresponding AAV3A polypeptide, or to the corresponding polypeptide of a different AAV serotype is useful (column 22, lines 23- 26). Therefore, an antibody specific for AAV3 would not be cross reactive due to the unique epitopes AAV serotype 2.
Asokan teaches modification of AAV capsid proteins and capsids comprising the same that can be incorporated into viral vectors to confer a phenotype of evasion of neutralizing antibodies without decreased transduction efficiency (page 1, lines 17-20). Asokan teaches the viral capsid can contain modifications, including insertions, deletions and/or substitutions. The amino acid substitutions can include glycine, alanine, valine, leucine, threonine and isoleucine (page 11, lines 15-20 and Table 2).
Amino acid positions 472, 587, and 706 of SEQ ID NO: 4 correspond to 471, 586, and 705 of Asokan. Asokan teaches an adeno-associated virus (AAV) capsid protein, wherein the capsid protein comprises a substitution resulting in the amino acid sequence where the amino acid at position 471 is any other amino acid than R (page 184, claim 192). Asokan teaches the amino acid corresponding to position 586 is any amino acid other than N (page 29, lines 1-10). Asokan further teaches another embodiment where the amino acid at position 586 is any amino acid other than S (page 129, claim 35). Asokan teaches at position 705 can comprise a selective amino acid substitution (page 61, lines 6-10).Asokan teaches the substitutions at positions 471 corresponding to 472 (page 184, claim 192), 586 corresponding to 587 (page 29, lines 1-10), and 705 corresponding to 706 (page 61, lines 6-10), which can be alanine as shown in SEQ ID NO:4 of the present application.
One of ordinary skill in the art would have been motivated to combine the adeno associated viral vector comprising a capsid protein, as taught by Russel with further modification of AAV capsid proteins as taught by Asokan. One would have been motivated to make this combination as modification of the capsid amino acids would confer vector evasion of neutralizing antibodies without decreasing transduction efficiency as taught by Asokan (page 2, lines 1-2). There is a reasonable expectation of success because the modification of capsid proteins had not decreased transduction efficiency in Asokan (page 1, lines 17-20) and further the AAV viral vectors taught by Russel and Asokan would be interchangeable. The modifications of Asokan to the sequence taught by Russel make obvious SEQ ID NO:4 of the present invention.
Rejection maintained (claim mapping updated for amino acid position correction):
Claims 1 and 7-12 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al (US 7,282,199 B2) in view of Asokan (WO 2017/ 058892 A2).
Regarding claims 1 and 9, Gao et al teach an adeno-associated viral vector (AAV) comprising a capsid protein sequence which has at least one of serine at position 472, serine at position 587 and asparagine at position 706 in the amino acid, which is represented by sequence 6 (columns 57-61). Sequence 6 of Gao reads on SEQ ID NO: 2 of the present application. Gao does not teach substitution of lysine, alanine, valine, leucine, threonine or isoleucine at each position.
Asokan teaches modification of AAV capsid proteins and capsids comprising the same that can be incorporated into viral vectors to confer a phenotype of evasion of neutralizing antibodies without decreased transduction efficiency (page 1, lines 17-20). Asokan teaches the viral capsid can contain modifications, including insertions, deletions and/or substitutions. The amino acid substitutions can include glycine, alanine, valine, leucine, threonine and isoleucine (page 11, lines 15-20 and Table 2).
Amino acid positions 472, 587, and 706 of SEQ ID NO: 4 correspond to 471, 586, and 705 of Asokan. Asokan teaches an adeno-associated virus (AAV) capsid protein, wherein the capsid protein comprises a substitution resulting in the amino acid sequence where the amino acid at position 471 is any other amino acid than R (page 184, claim 192). Asokan teaches the amino acid corresponding to position 586 is any amino acid other than N (page 29, lines 1-10). Asokan further teaches another embodiment where the amino acid at position 586 is any amino acid other than S (page 129, claim 35). Asokan teaches at position 705 can comprise a selective amino acid substitution (page 61, lines 6-10).Asokan teaches the substitutions at positions 471 corresponding to 472 (page 184, claim 192), 586 corresponding to 587 (page 29, lines 1-10), and 705 corresponding to 706 (page 61, lines 6-10), which can be alanine as shown in SEQ ID NO:4 of the present application.
One of ordinary skill in the art would have been motivated to combine the adeno associated viral vector comprising a capsid protein as taught by Gao with further modification of AAV capsid proteins as taught by Asokan. One would have been motivated to make this combination because this modification would confer evasion of the vector from neutralizing antibodies without decreasing transduction efficiency as taught by Asokan (page 2, lines 1-2). There is a reasonable expectation of success because the modification of capsid proteins had not decreased transduction efficiency in Asokan (page 1, lines 17-20) and further the AAV viral vectors taught by Gao and Asokan would be interchangeable. The modifications of Asokan to the sequence taught by Gao make obvious SEQ ID NO:4 of the present invention. Furthermore, Asokan teaches various modifications of the capsid protein.
Regarding claim 7, Gao teaches a viral vector wherein the tissue-specific promoter is a liver-specific promoter (column 70, claim 13).
Regarding claim 8, Gao teaches an adeno-associated viral vector where the liver-specific promoter could be a promoter for albumin (column 11, and lines 24-26). Gao teaches the use of various VP1 capsid proteins, which includes various serotypes like AAV2 (column 4, lines 41-53). Furthermore, the use of VP1 protein of AAV2 SEQ ID NO:4 for the capsid of Gao (column 5, lines 34-35) which reads on SEQ ID NO: 1 of the present application.
Regarding claim 10, Gao et al teaches a polynucleotide coding for serine at position 472, serine at position 587 and asparagine at position 706 in the amino acid, which is represented by sequence 6 (columns 57-61). Sequence 6 of Gao reads on SEQ ID NO: 2 of the present application. Gao does not teach substitution of lysine, alanine, valine, leucine, threonine or isoleucine at each position.
Asokan teaches modification of AAV capsid proteins and capsids comprising the same that can be incorporated into virus vectors to confer a phenotype of evasion of neutralizing antibodies without decreased transduction -efficiency (page 1, lines 17-20). Asokan teaches the viral capsid can contain modifications, including insertions, deletions and/or substitutions. The amino acid substitutions can include glycine, alanine, valine, leucine, threonine and isoleucine (page 11, lines 15-20 and Table 2).
Amino acid positions 472, 587, and 706 of SEQ ID NO: 4 correspond to 471, 586, and 705 of Asokan. Asokan teaches an adeno-associated virus (AAV) capsid protein, wherein the capsid protein comprises a substitution resulting in the amino acid sequence where the amino acid at position 471 is any other amino acid than R (page 184, claim 192). Asokan teaches the amino acid corresponding to position 586 is any amino acid other than N (page 29, lines 1-10). Asokan further teaches another embodiment where the amino acid at position 586 is any amino acid other than S (page 129, claim 35). Asokan teaches at position 705 can comprise a selective amino acid substitution (page 61, lines 6-10).Asokan teaches the substitutions at positions 471 corresponding to 472 (page 184, claim 192), 586 corresponding to 587 (page 29, lines 1-10), and 705 corresponding to 706 (page 61, lines 6-10), which can be alanine as shown in SEQ ID NO:4 of the present application.
One of ordinary skill in the art would have been motivated to combine polypeptide sequence encoding a capsid protein, as taught by Gao with further modification of AAV capsid proteins as taught by Asokan. One would have been motivated to make this combination as modification of the capsid amino acids would confer evasion of neutralizing antibodies without decreasing transduction efficiency as taught by Asokan (page 2, lines 1-2). There is a reasonable expectation of success because the changing of capsid proteins had not decreased transduction efficiency in Asokan (page 1, lines 17-20) and further the polypeptides encoding capsid proteins taught by Gao and Asokan would be interchangeable. The modifications of Asokan to the sequence taught by Gao make obvious SEQ ID NO:4 of the present invention. Furthermore, Asokan teach various modifications of the capsid protein and the benefits related.
Regarding claim 11, Gao teaches a pharmaceutical composition for transferring genes into a liver of a subject comprising an adeno-associated viral vector (column 17, lines 5-25 and 54-55).
Regarding claim 12, Gao teaches viral vectors and administration to a human subject (column 17, lines 27-31).
Response to Arguments
Applicant's arguments filed 03/04/2026 have been fully considered but they are not persuasive.
Applicant’s Arguments: Applicant argues the present SEQ ID NO: 4 and the AAV2 protein of Asokan do not line up, so that positions 472, 587, and 706 of Asokan are not the same as positions 472, 587, and 706 of presently claimed SEQ ID NO: 4. Applicant points out the misalignment is because there is a gap between positions 449 and 450 in AAV2 of Asokan. Applicant further points out the gap means that the numbering of residues of AAV2 after 449 is off by one, so that 472, 587, and 706 of SEQ ID NO: 4 actually correspond to 471, 586, and 705 of Asokan. Therefore, Asokan does not teach or suggest alanine in the AAV3B capsid at positions 472, 587, and 706 as defined in SEQ ID NO: 4.
Examiner’s Response: Examiner appreciated the misalignment of Seq ID NO:4 and AAV2. Asokan is maintained as it still covers the changes at positions 472, 587, and 796 of SEQ ID NO:4. As applicant has pointed out 472, 587, and 706 of SEQ ID NO: 4 correspond to 471, 586, and 705 of Asokan. Asokan teaches an adeno-associated virus (AAV) capsid protein, wherein the capsid protein comprises a substitution resulting in the amino acid sequence where the amino acid at position 471 is any other amino acid than R (page 184, claim 192). Asokan teaches the amino acid corresponding to position 586 is any amino acid other than N (page 29, lines 1-10). Asokan further teaches another embodiment where the amino acid at position 586 is any amino acid other than S (page 129, claim 35). Asokan teaches at position 705 can comprise a selective amino acid substitution (page 61, lines 6-10).
Applicants Arguments: Applicant argues SEQ ID NO: 4 provides improved transfection of wild type AAV3 in the presence of AAV2 antisera. Applicant argues these results are unexpected.
Examiner’s Response: Asokan teaches modification of AAV capsid proteins and capsids to specifically confer a phenotype of evasion of neutralizing antibodies without decreased transduction efficiency (page 1, lines 17-20). Therefore, the improved transfection would not have been a surprising result.
Rejection maintained:
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claim 10 of this application is patentably indistinct from claim 10 of Application No. 18/285829. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
Response to Arguments
Applicant's arguments filed 03/04/2026 have been fully considered but they are not persuasive.
Applicant Argues: The Office Action alleges that claim 10 of this application is patentable indistinct from claim 10 of Application No. 18/285,829. Applicant respectfully traverses the rejection. The presently claimed subject matter is believed to be patentably distinct from the claims of the copending application at least in view of differences in claim scope and the specific combination and arrangement of features recited herein.
Examiner’s response: Both claim 10 of Application No. 18/285,829 and claim 10 of the present application recite a polynucleotide coding for any one of the following sequences: an amino acid sequence capsid protein in which 1-3 amino acid residues at other than position 472, position 587 and position 706 in the amino acid sequence of SEQ ID NO: 4 are deleted, substituted, inserted or added; or the amino acid sequence of a mutated AAV3B capsid protein, which is represented by SEQ ID NO: 4.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635
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