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 .
Restriction/Election
Applicants’ election of Group I claims 1, 4-6, 8-9, 30 on September 16, 2026 is acknowledged. Claims 7, 10-29 and 31 were canceled. Claims 1, 4-6, 8-9, 30 are pending and under examination in this Office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/14, 2026, 5/19/2026, 8/15/2025, 5/20, 2025, 4/29/2025, 4/17/2025, 3/11/2025, 2/25/2025, 12/31/2024, 12/10/2024, 11/15/2024, 10/03/2024, 9/13/2024, 7/11/2024, 6/27/2024, 3/26/2024, 3/18/2024, 2/08/2024 and 1/4/2024 have been considered by the examiner.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 4-5, 8-9, 30 are rejected u under 35 U.S.C. 103 as being unpatentable over Wilson et al. (US Patent 7,906,111) in view of Rubenfield (US Patent 6,551,795).
Regarding claims 1, 4-5, 8-9. Wilson teaches AAV-based constructs for delivery of heterologous molecules, AAV9, and VP1 (see Example 3). AAV capsid protein comprising a sequence identical with present SEQ ID NO: 14 (see sequence alignment below). These vectors and other vectors described herein can further contain a minigene comprising a selected transgene which is flanked by AAV 5' ITR and AAV 3' ITR (see Examples 1-8 and claims 1-7).
Regarding claim 30. Wilson teaches AAV-based constructs comprising a transgene nucleic acid sequence selected from insulin, glucagon, growth hormone (GH), parathyroid hormone (PTH), growth hormone releasing factor (GRF), follicle stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotropin (hCG), vascular endothelial growth factor (VEGF), angiopoietins, angiostatin, granulocyte colony stimulating factor (GCSF), erythropoietin (EPO), connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin growth factors I and II (IGF-I and IGF-II), any one of the transforming growth factor a superfamily, including TGF.alpha., activins, inhibins, or any of the bone morphogenic proteins (BMP) BMPs 1-15, any one of the heregluin/neuregulin/ARIA/neu differentiation factor (NDF) family of growth factors, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophins NT-3 and NT-4/5, ciliary neurotrophic factor (CNTF), glial cell line derived neurotrophic factor (GDNF), neurturin, agrin, any one of the family of semaphorins/collapsins, netrin-1 and netrin-2, hepatocyte growth factor (HGF), ephrins, noggin, sonic hedgehog and tyrosine hydroxylase (see columns 17-33).
Present SEQ ID NO: 14
Query Match 100.0%; Score 3986; Length 736;
Best Local Similarity 100.0%;
Matches 736; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Qy 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
Qy 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
Qy 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
Qy 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
Qy 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP 480
Qy 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS 540
Qy 541 LIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQG 600
Qy 601 ILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPT 660
Qy 661 AFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGV 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGV 720
Qy 721 YSEPRPIGTRYLTRNL 736
||||||||||||||||
Db 721 YSEPRPIGTRYLTRNL 736
Rubenfield discloses a sequence comprising present SEQ ID NO: 1 derived from Pseudomonas Aeruginosa used for diagnostic and therapeutic purposes and expression of the peptide in the nucleic acids (see SEQ ID NO: 30331, claims 1-26 and columns 19-25).
Present SEQ ID NO: 1 and SEQ ID NO: 30331 in Rubenfield
Query Match 100.0%; Score 43; Length 175;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 PRPPSTH 7
|||||||
Db 169 PRPPSTH 175
It would have been prima facie obvious to provide Wilson’s AAV construct comprising Rubenfield sequence comprising a sequence identical with present SEQ ID NO: 1 because Rubenfield teaches that SEQ ID NO: 1, derived from Pseudomonas Aeruginosa, can be used for diagnostic and therapeutic purposes when expressed in nucleic acids (see columns 19-25).
Thus, the present invention would have been prima facie obvious at the time the invention was made.
Claims 6 are rejected u under 35 U.S.C. 103 as being unpatentable over Wilson et al. (US Patent 7,906,111) in view of Rubenfield (US Patent 6,551,795) and further in view of Kleinschmidt et al. (US Patent 7,629,322).
Wilson et al. and Rubenfield teach the claimed invention as discussed above. They do not teach inserting the targeting sequence in a position corresponding to amino acids 588 and 589 of SEQ ID NO: 14.
Kleinschmidt et al. teaches that Arginine 585 and 588 are involved in Heparin binding on the AAV-2 capsid surface and the involvement of arginine 588 in heparin-binding came from the double point mutant #29 (N587A, R588C) which also resulted in more than 1000 fold reduction in infectivity, reduced cell binding and a loss of heparin binding (Table 1). For all the mutants analyzed in this report no significant effect on genome packaging was detected (Table 1). From these results, it was hypothesized that the loss of the basic charge of arginines 585 and 588 located in loop IV resulted in reduced cell binding and infectivity (see Example 2).
It would have been prima facie obvious to provide Wilson’s and Rubenfield’s AVV construct wherein the targeting sequence is inserted in position corresponding to amino acids 588 and 589 of SEQ ID NO: 14 because Kleinschmidt et al. teaches that Arginine 588 and 589 are involved in Heparin binding on the AAV-2 capsid surface and inserting the targeting sequence at position 588 would destroy the AAV virus natural affinity to bind heparin and thus infect the cells. Additionally, because position 588 is highly permissive and can accommodate insertions (see Example 2).
Thus, the present invention would have been prima facie obvious at the time the invention was made.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 4-6, 8-9, 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-15, and 21-22 of copending Application No. 19/116,185.
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are drawn to An adeno-associated virus (AAV) capsid protein comprising an amino acid sequence that comprises seven at least four contiguous amino acids from the sequence PRPPSTH (SEQ ID NO:1).
Claims 5-An adeno-associated virus (AAV) vector comprising (i) one or more of peptides selected from the group consisting of PRPPSTH (SEQ ID NO:1), MAEPGAR (SEQ ID NO:25), MLYADNT (SEQ ID NO: 26), and SQDPSTL (SEQ ID NO: 27), in its capsid, and (ii) a nucleic acid sequence comprising a smooth muscle cell-specific promoter or active portion thereof encapsulated by the capsid.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the present claims and the claims of the copending application are drawn to An adeno-associated virus (AAV) capsid protein comprising an amino acid sequence that comprises seven at least four contiguous amino acids from the sequence PRPPSTH (SEQ ID NO:1).
The difference between the present claims and the claims of the copending application is that the claims of the copending application recite multiple peptides while the claims of the present application are limited to one peptide of SEQ ID NO: 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4-6, 8-9, 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5-22 of copending Application No. 19/171,179.
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are drawn to An adeno-associated virus (AAV) capsid protein comprising an amino acid sequence that comprises seven at least four contiguous amino acids from the sequence PRPPSTH (SEQ ID NO:1).
The claims of the copenidng Application No. 19/171,179 are drawn to A recombinant adeno associated viral vector (AAV) encapsulating a construct encoding an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme, said vector comprising: an expression cassette comprising: a 5′ ITR; a promoter; a nucleic acid encoding an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme; and a 3′ ITR; and wherein the recombinant AAV vector comprises a capsid with a nucleic encoding peptide sequence PRPPSTH (SEQ ID NO:44) inserted therein.
The difference between the present claims and the claims of the copending application is that the claims of the copending application recite additional components of the construct, such as pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme, said vector comprising: an expression cassette comprising: a 5′ ITR; a promoter; a nucleic acid encoding an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme; and a 3′ ITR, while the claims of the present application are limited to one peptide of SEQ ID NO: 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM.
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/AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648
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