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 .
Election/Restrictions
Applicant’s amendment submitted on 12/1/2025 is acknowledged. Claims 46-49, 51, and 53 are canceled. New claim 59 is added.
Applicant’s election without traverse of Inventive Group VII (claim 52) and the required species in the reply filed on 4/8/2025 is acknowledged. New claims 54-58 are added. However, upon further consideration, the examiner hereby finds that Unity of Invention is present between the compositions of the instant invention, including Groups I-III & V-VIII. Accordingly, Inventive Groups I-III and V-VIII are hereby rejoined. New Claims 55 and 58 belong to the elected inventive Group VII.
Claims 56 and 57 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/8/2025.
Applicant elected the following species:
A variant VP1 capsid protein amino acid sequence: SEQ ID NO: 23. Upon further consideration, and in the interest of compact prosecution, the examiner hereby withdraws the election of species requirement.
Amended claims 52 and 54-59 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 12/1/2025 is in compliance with 37 CFR 1.97. Accordingly, the IDSs are being considered by the examiner.
Claim Interpretation
The specification indicates that the term “variant” refers to a first composition (e.g., a first molecule), that is related to a second composition (e.g., a second molecule, also termed a “parent” molecule). The variant molecule can be derived from, isolated from, based on or homologous to the parent molecule. Spec., p. 3.
The specification indicates that the term “transgene” refers to a polynucleotide that is introduced into a cell and is capable of being transcribed into RNA and optionally, translated and/or expressed under appropriate conditions. In aspects, it confers a desired property to a cell into which it is introduced, or otherwise leads to a desired therapeutic outcome. In another aspect, it may be transcribed into a molecule that mediates RNA interference, such as miRNA, siRNA, or shRNA. Spec., p. 8.
Withdrawn Objections
The previous objections are hereby withdrawn due to the amendment submitted 12/1/2025:
Claim objections: claims 48, 51-53, 55, and 58 for minor informalities.
New Objections Necessitated by Amendment
Claim 59 is objected to because of the following informalities: claim 59 recites the preamble “A pharmaceutical composition according to claim 58”, but should instead recite “The pharmaceutical composition according to claim 58”. Appropriate correction is required.
Withdrawn Rejections
The previous rejections are hereby withdrawn due to amendment or cancellation of the claims:
Claim Rejections – 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 46-48, 51, 54, and 58 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
MPEP 2173.05(s) states:
[Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims. Generally, the presence or absence of such reference characters does not affect the scope of a claim. See MPEP § 608.01(m) for information pertaining to the treatment of reference characters in a claim.] Presently, the claimed information of “at least one mutation selected from Table 1” on line 2 of claim 46 does not meet the requirements of an “exceptional circumstances where there is no practical way to define the invention in words”. Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Claims 47-48 are also rejected since they depend on claim 46, but do not remedy this deficiency.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 48 recites the broad recitation “an adeno-associated virus (AAV) that comprises at least one capsid protein according to claim 46”, and the claim also recites “in particular a rAAV further comprising a heterologous nucleic acid comprising a transgene” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 47 and 54 recite “a polynucleotide that encodes for a variant capsid protein according to [claim 46 or claim 52]”. However, claims 46 and 52, upon which claims 47 and 54 depend, are drawn to a variant VP1 capsid protein. It is not clear if claims 47 and 54 mean a polynucleotide that encodes the variant VP1 capsid protein of claims 46 and 52, or rather a variant of such VP1 capsid protein.
Claims 51 and 58 are indefinite because they include the limitation “sustained-release matrices, such as biodegradable polymers”, but it is unclear whether the intended scope of the claim is biodegradable polymers or other sustained-release matrices.
Regarding claims 51 and 58, the phrase “such as” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Maintained Rejections
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Previous Rejection Maintained in Part) Claims 52, 54-55, and 58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. (J Virol. 2000 Sep;74(18):8635-47. doi: 10.1128/jvi.74.18.8635-8647.2000. PMID: 10954565; hereinafter referred to as “Wu”). The rejection of claims 46-48, 51, and 53 is withdrawn due to cancellation of those claims.
The claimed invention encompasses a variant VP1 capsid protein that has an amino acid sequence selected from the group consisting of: SEQ ID NO: 23, or a derived variant VP2 or variant VP3 capsid protein, as recited in claim 52, a polynucleotide that encodes for the variant capsid protein, as recited in claim 54, or an adeno-associated virus (AAV) that comprises at least one of the capsid proteins, further comprising a heterologous nucleic acid comprising a transgene, as recited in claim 55. Alternatively, the invention encompasses a pharmaceutical composition comprising an rAAV comprising a variant VP1 capsid protein that has an amino acid sequence selected from the group consisting of: SEQ ID NO: 23, or a derived variant VP2 or variant VP3 capsid protein, and a heterologous nucleic acid comprising a transgene, with pharmaceutically acceptable excipients, and optionally sustained-release matrices, such as biodegradable polymers, as recited in claim 58.
The Prior Art
Wu teaches a comprehensive genetic map of the AAV capsid gene, featuring 93 mutants at 59 different positions in the AAV capsid gene constructed by site-directed mutagenesis (Abstract; Fig. 1). The mutants included 12 with mutations exclusively in VP1, 5 in VP2, and the remainder in VP3 (Fig. 1; p. 8637, col. 2, para. 1; Table 1). Recombinant AAV vectors were generated bearing the capsid mutation, with AAV plasmid that contains the gfp gene under the control of a CMV enhancer-promoter and a pIM45 plasmid bearing the mutation (p. 8638, col. 1, para. 2; Wu, generally).
Therefore, Wu anticipates Claims 52, 54-55, and 58.
After careful consideration, Applicants’ arguments are found not to be persuasive.
Applicant’s presents the following arguments:
Independent claim 52 is amended herein such that the claimed variant VP1 capsid proteins are those of SEQ ID NO: 23, or a derived VP2 or VP3 capsid protein thereof. Wu does not specifically disclose SEQ ID NO: 23 or VP2 or VP3 capsid protein derived thereof as recited in amended claim 52. To reject a claim as anticipated by a reference, the disclosure must teach every element required by the claim under its broadest reasonable interpretation. MPEP §2144. Applicant therefore submits that the claims are not anticipated by Wu. It should also be noted that SEQ ID NO: 23 corresponds to a sequence tested in the Examples of the specification, and de-targets the liver (Fig. 2 of the specification), and displays a marked tropism for the tested tissues. Wu does not teach or suggest the properties of these capsids.
Applicant’s arguments are not persuasive because:
The specification indicates that the term “variant” refers to a first composition (e.g., a first molecule), that is related to a second composition (e.g., a second molecule, also termed a “parent” molecule). The variant molecule can be derived from, isolated from, based on or homologous to the parent molecule. Spec., p. 3. In applying the broadest reasonable interpretation of the claim limitation “derived variant VP2 or variant VP3 capsid protein” (claim 52), the AAV capsid gene mutants disclosed by Wu read on homologous VP2 or VP3 variants of SEQ ID NO: 23 (the currently examined species). The broadest reasonable interpretation of the claim limitation “derived variant VP2 or variant VP3 capsid protein” encompasses any AAV capsid VP2 or VP3. Accordingly, Applicants’ arguments are not persuasive, and Wu anticipates claims 52, 54-55, and 58.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
(Previous Rejection Maintained in Part) Claims 52, 55, and 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12037362 B2. The rejection of claims 46, 48, 51, and 53 is withdrawn due to cancellation of those claims. Although the claims at issue are not identical, they are not patentably distinct from each other because each set of claims is drawn to an AAV capsid protein, which may be a variant VP2 or variant VP3 capsid protein in the instant application (claim 52) or a hybrid AAV capsid protein which is a hybrid VP2 or VP3 protein in ‘362 (claim 2). Both the instant claims (claim 55) and ‘362 claims (claims 3 and 4) encompass AAV vectors comprising the AAV capsid protein.
Additionally, the instant specification indicates that the term “variant” (present in the instant claims) refers to a first composition (e.g., a first molecule), that is related to a second composition (e.g., a second molecule, also termed a “parent” molecule). The variant molecule can be derived from, isolated from, based on or homologous to the parent molecule. Specification, p. 3. The Examiner thus interprets the hybrid VP2 or VP3 proteins disclosed by ‘362 to read on the instant claims’ limitation “a derived variant VP2 or variant VP3 capsid protein”.
Although ‘362 does not specifically indicate that its pharmaceutical composition comprising a therapeutically effective amount of AAV vector particles (claim 5) comprises pharmaceutically acceptable excipients (as required by instant claim 58), the presence of such excipients would be inherent to the invention, since ‘362 teaches methods of treating a disease by gene therapy, comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition comprising AAV (‘362 claims 6-7).
Although ‘362 does not specifically disclose that the AAV vector particle packaging a gene of interest which comprises one or more of the hybrid recombinant AAV capsid proteins is a hybrid VP2 or VP3 protein (claims 3-4), it would be obvious to one of ordinary skill in the art since ‘362 discloses: i) recombinant hybrid AAV capsid protein which is a hybrid VP2 or VP3 protein ii) AAV vector particles which comprise one or more hybrid AAV capsid proteins, and iii) pharmaceutical compositions comprising a therapeutically effective amount of AAV vector particles.
After careful consideration, Applicants’ arguments are found not to be persuasive.
Applicant’s presents the following arguments:
The reference patent claims a recombinant AAV capsid protein, which is a hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins, wherein: said recombinant hybrid AAV capsid protein comprises the sequence of SEQ ID NO: 3, wherein said recombinant hybrid AAV capsid protein has a reduced liver tropism compared to the parent AAV9 and AAVrh74 capsid proteins, and the muscle tropism of the parent AAV9 and/or AAVrh74 capsid proteins is maintained in the recombinant hybrid AAV capsid protein.
To the contrary, the pending claims are directed to capsid proteins of SEQ ID NO: 23 or a derived VP2 or VP3 capsid protein thereof. This claimed variant VP1 protein amino acid sequence is not a hybrid between AAV9 and AAVrh74 capsid proteins and is different from SEQ ID NO: 3 as recited in the claims of the reference patent. The test for obvious-type double patenting is whether the claims of the pending application are patentably distinct from the claims of the cited reference application or patent. See MPEP§804. In the present rejection, Applicant submits that the claims at issue are patentably distinct over the claims in the reference patent for at least the following reasons. The pending claims have different claim scope and elements when compared to the claims of this reference application. For example, the claims in the reference patent require SEQ ID NO: 3 which is a hybrid sequence as mentioned above. The pending claims of the present application do not teach nor suggest such features. Second, the pending claims are directed to a different inventive concept than those of the reference patent. While the claims of the reference application relate to hybrid sequences, the claims of the present application do not require such a feature as they relate to variant VP1 capsid proteins.
Applicant’s arguments are not persuasive because:
The specification indicates that the term “variant” refers to a first composition (e.g., a first molecule), that is related to a second composition (e.g., a second molecule, also termed a “parent” molecule). The variant molecule can be derived from, isolated from, based on or homologous to the parent molecule. Spec., p. 3. In applying the broadest reasonable interpretation of the claim limitation “derived variant VP2 or variant VP3 capsid protein” (claim 52), the AAV capsid gene mutants disclosed by Wu read on homologous VP2 or VP3 variants of SEQ ID NO: 23 (the currently examined species). The broadest reasonable interpretation of the claim limitation “derived variant VP2 or variant VP3 capsid protein” encompasses any AAV capsid VP2 or VP3. Accordingly, Applicants’ arguments are not persuasive, and the AAV capsid variants of the copending application read on the instant claims.
(Previous Rejection Maintained in Part) Claims 52, 54-55, and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-17 of copending Application No. 18/735,636 (reference application). The rejection of claims 46-48, 51, and 53 is withdrawn due to cancellation of those claims. Although the claims at issue are not identical, they are not patentably distinct from each other because each set of claims is drawn to an AAV capsid protein, which may be a variant VP2 or variant VP3 capsid protein in the instant application (claim 52) or a recombinant chimeric AAV capsid protein that is a chimeric VP2 protein comprising a VP2-specific N-terminal region having a sequence from natural or artificial AAV serotype other than AAV9 and AAVrh74, and a VP3 C-terminal region having the sequence of a hybrid VP3 protein (‘636 claim 10). Additionally, each set of claims encompasses a polynucleotide encoding the AAV capsid protein (instant claim 54; ‘636 claim 11). Further, both the instant claims (claim 55) and ‘636 claims (claims 13 and 44) encompass AAV vectors comprising the capsid protein.
Additionally, the instant specification indicates that the term “variant” (present in the instant claims) refers to a first composition (e.g., a first molecule), that is related to a second composition (e.g., a second molecule, also termed a “parent” molecule). The variant molecule can be derived from, isolated from, based on or homologous to the parent molecule. Specification, p. 3. The Examiner thus interprets the chimeric VP2 and VP3 proteins disclosed by ‘636 to read on the instant claims’ limitation “a derived variant VP2 or variant VP3 capsid protein”.
Although ‘636 does not specifically indicate that its pharmaceutical composition comprising a therapeutically effective amount of AAV vector particles (claims 15-17) comprises pharmaceutically acceptable excipients (as required by instant claim 58), the presence of such excipients would be inherent to the invention, since ‘636 teaches that its pharmaceutical composition is for use as a medicament in gene therapy for treating genetic diseases, cancer or auto-immune diseases affecting muscle tissues (‘636 claim 16).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
After careful consideration, Applicants’ arguments are found not to be persuasive.
Applicant’s presents the following arguments:
Similar to U.S. Patent No. 12,037,362 discussed above, the reference application claims are directed to a recombinant adeno-associated virus (AAV) capsid protein, which is a hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins. The claimed amino acid sequences herein do not correspond to such hybrid sequences as they are VP1 variant protein amino acid sequences as discussed above.
Applicant’s arguments are not persuasive because:
The specification indicates that the term “variant” refers to a first composition (e.g., a first molecule), that is related to a second composition (e.g., a second molecule, also termed a “parent” molecule). The variant molecule can be derived from, isolated from, based on or homologous to the parent molecule. Spec., p. 3. In applying the broadest reasonable interpretation of the claim limitation “derived variant VP2 or variant VP3 capsid protein” (claim 52), the AAV capsid gene mutants disclosed by Wu read on homologous VP2 or VP3 variants of SEQ ID NO: 23 (the currently examined species). The broadest reasonable interpretation of the claim limitation “derived variant VP2 or variant VP3 capsid protein” encompasses any AAV capsid VP2 or VP3. Accordingly, Applicants’ arguments are not persuasive, and the AAV capsid variants of the copending application read on the instant claims.
New Rejections
Double Patenting
(New Rejection Necessitated by Amendment) Claims 52, 55, and 58-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12037362 B2 in view of Jang et al. (Mol Ther. 2011 Aug;19(8):1407-15. doi: 10.1038/mt.2011.111. Epub 2011 May 31. PMID: 21629221). Although the claims at issue are not identical, they are not patentably distinct from each other because each set of claims is drawn to an AAV capsid protein, which may be a variant VP2 or variant VP3 capsid protein in the instant application (claim 52) or a hybrid AAV capsid protein which is a hybrid VP2 or VP3 protein in ‘362 (claim 2). Both the instant claims (claim 55) and ‘362 claims (claims 3 and 4) encompass AAV vectors comprising the AAV capsid protein.
Additionally, the instant specification indicates that the term “variant” (present in the instant claims) refers to a first composition (e.g., a first molecule), that is related to a second composition (e.g., a second molecule, also termed a “parent” molecule). The variant molecule can be derived from, isolated from, based on or homologous to the parent molecule. Specification, p. 3. The Examiner thus interprets the hybrid VP2 or VP3 proteins disclosed by ‘362 to read on the instant claims’ limitation “a derived variant VP2 or variant VP3 capsid protein”.
Although ‘362 does not specifically indicate that its pharmaceutical composition comprising a therapeutically effective amount of AAV vector particles (claim 5) comprises pharmaceutically acceptable excipients (as required by instant claim 58), the presence of such excipients would be inherent to the invention, since ‘362 teaches methods of treating a disease by gene therapy, comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition comprising AAV (‘362 claims 6-7).
Although ‘362 does not specifically disclose that the AAV vector particle packaging a gene of interest which comprises one or more of the hybrid recombinant AAV capsid proteins is a hybrid VP2 or VP3 protein (claims 3-4), it would be obvious to one of ordinary skill in the art since ‘362 discloses: i) recombinant hybrid AAV capsid protein which is a hybrid VP2 or VP3 protein ii) AAV vector particles which comprise one or more hybrid AAV capsid proteins, and iii) pharmaceutical compositions comprising a therapeutically effective amount of AAV vector particles.
Notably, the copending claims do not disclose a pharmaceutical composition comprising an rAAV comprising at least one capsid protein according to claim 52 and a heterologous nucleic acid comprising a transgene, with pharmaceutically acceptable excipients and sustained-release matrices that are biodegradable polymers.
Jang teaches that viral vectors can be combined with biomaterials either through encapsulation within the material or immobilization onto a material surface, and subsequent biomaterial-based delivery can increase the vector’s residence time within the target site through releasing vectors in a sustained manner, thereby potentially providing localized delivery, enhancing transduction, and extending the duration of gene expression (Abstract; p. 1407, col. 2, para. 1). Jang also discloses that a number of biomaterial platforms have been harnessed for applications, including synthetic, biodegradable polymers such as poly lactide-co-glycolide (p. 1409, col. 1, paras. 2-3).
It would be obvious to one of ordinary skill in the art to modify the copending pharmaceutical compositions comprising AAV vector particles to comprise sustained-release matrices that are biodegradable polymers.
(New Rejection Necessitated by Amendment) Claims 52, 54-55, and 58-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-17 of copending Application No. 18/735,636 (reference application) in view of Jang et al. (Mol Ther. 2011 Aug;19(8):1407-15. doi: 10.1038/mt.2011.111. Epub 2011 May 31. PMID: 21629221). Although the claims at issue are not identical, they are not patentably distinct from each other because each set of claims is drawn to an AAV capsid protein, which may be a variant VP2 or variant VP3 capsid protein in the instant application (claim 52) or a recombinant chimeric AAV capsid protein that is a chimeric VP2 protein comprising a VP2-specific N-terminal region having a sequence from natural or artificial AAV serotype other than AAV9 and AAVrh74, and a VP3 C-terminal region having the sequence of a hybrid VP3 protein (‘636 claim 10). Additionally, each set of claims encompasses a polynucleotide encoding the AAV capsid protein (instant claim 54; ‘636 claim 11). Further, both the instant claims (claim 55) and ‘636 claims (claims 13 and 44) encompass AAV vectors comprising the capsid protein.
Additionally, the instant specification indicates that the term “variant” (present in the instant claims) refers to a first composition (e.g., a first molecule), that is related to a second composition (e.g., a second molecule, also termed a “parent” molecule). The variant molecule can be derived from, isolated from, based on or homologous to the parent molecule. Specification, p. 3. The Examiner thus interprets the chimeric VP2 and VP3 proteins disclosed by ‘636 to read on the instant claims’ limitation “a derived variant VP2 or variant VP3 capsid protein”.
Although ‘636 does not specifically indicate that its pharmaceutical composition comprising a therapeutically effective amount of AAV vector particles (claims 15-17) comprises pharmaceutically acceptable excipients (as required by instant claim 58), the presence of such excipients would be inherent to the invention, since ‘636 teaches that its pharmaceutical composition is for use as a medicament in gene therapy for treating genetic diseases, cancer or auto-immune diseases affecting muscle tissues (‘636 claim 16).
Notably, the copending claims do not disclose a pharmaceutical composition comprising an rAAV comprising at least one capsid protein according to claim 52 and a heterologous nucleic acid comprising a transgene, with pharmaceutically acceptable excipients and sustained-release matrices that are biodegradable polymers.
Jang teaches that viral vectors can be combined with biomaterials either through encapsulation within the material or immobilization onto a material surface, and subsequent biomaterial-based delivery can increase the vector’s residence time within the target site through releasing vectors in a sustained manner, thereby potentially providing localized delivery, enhancing transduction, and extending the duration of gene expression (Abstract; p. 1407, col. 2, para. 1). Jang also discloses that a number of biomaterial platforms have been harnessed for applications, including synthetic, biodegradable polymers such as poly lactide-co-glycolide (p. 1409, col. 1, paras. 2-3).
It would be obvious to one of ordinary skill in the art to modify the copending pharmaceutical compositions comprising AAV vector particles to comprise sustained-release matrices that are biodegradable polymers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
New Rejection
Claim Rejections - 35 USC § 103
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.
(New Rejection Necessitated by Amendment) Claim 59 is rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (supra), as applied to claims 52, 54-55, and 58 above, in view of Jang et al. (Mol Ther. 2011 Aug;19(8):1407-15. doi: 10.1038/mt.2011.111. Epub 2011 May 31. PMID: 21629221; hereinafter referred to as “Jang”).
The claimed invention encompasses a pharmaceutical composition comprising an rAAV comprising a variant VP1 capsid protein that has an amino acid sequence selected from the group consisting of: SEQ ID NO: 23, or a derived variant VP2 or variant VP3 capsid protein, and a heterologous nucleic acid comprising a transgene, with pharmaceutically acceptable excipients, and a sustained-release matrices that are biodegradable polymers, as recited in claim 59.
The Prior Art
Wu teaches a comprehensive genetic map of the AAV capsid gene, featuring 93 mutants at 59 different positions in the AAV capsid gene constructed by site-directed mutagenesis (Abstract; Fig. 1). The mutants included 12 with mutations exclusively in VP1, 5 in VP2, and the remainder in VP3 (Fig. 1; p. 8637, col. 2, para. 1; Table 1). Recombinant AAV vectors were generated bearing the capsid mutation, with AAV plasmid that contains the gfp gene under the control of a CMV enhancer-promoter and a pIM45 plasmid bearing the mutation (p. 8638, col. 1, para. 2; Wu, generally). Wu also discloses that AAV can transduce a wide variety of tissues (p. 8636, col. 1, para. 2), and is a valuable vector for gene therapy (Abstract).
However, Wu does not teach sustained-release matrices that are biodegradable polymers.
Jang teaches that viral vectors can be combined with biomaterials either through encapsulation within the material or immobilization onto a material surface, and subsequent biomaterial-based delivery can increase the vector’s residence time within the target site through releasing vectors in a sustained manner, thereby potentially providing localized delivery, enhancing transduction, and extending the duration of gene expression (Abstract; p. 1407, col. 2, para. 1). Jang also discloses that a number of biomaterial platforms have been harnessed for applications, including synthetic, biodegradable polymers such as poly lactide-co-glycolide (p. 1409, col. 1, paras. 2-3).
It would have been obvious to one of ordinary skill in the art to modify Wu’s AAV compositions to include a biodegradable polymer such as poly lactide co-glycolide for sustained release. Wu discloses that AAV is a valuable vector for gene therapy and can transduce a wide variety of tissues, while Jang teaches that viral vectors can be combined with biomaterials, such as biodegradable polymers, to increase the vector’s time within the target site in a sustained manner, thereby potentially providing localized delivery, enhancing transduction, and extending the duration of gene expression. One of ordinary skill in the art would have been motivated to provide localized delivery, enhancing transduction, and extending the duration of gene expression of the AAV vector. There would be a reasonable expectation of success because Jang discloses use of biomaterial-based delivery for viral vectors. Therefore, claim 59 was prima facie obvious before the priority date of the instant invention.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is (571)272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671