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 .
Application Status
This action is written in response to applicant’s correspondence received on 10/29/2024. Claims 1-24, 27-29 are currently pending.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US2022/075871 filed on 09/01/2022 and has PRO 63/239,650 filed on 09/01/2021.
Specification
5. The use of the terms GenBank, Unigene, Entrez, Elsevier, PubMed, which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
6. Claims 2-6, 9-12, 23-24 are objected to because of the following informalities:
Regarding claims 2-4, 9-12, 23-24, the recitation “SEQ ID NO.:” is inconsistent with the rest of the disclosure for including a period “.” Before “:”. Editing to “SEQ ID NO:” is recommended.
Regarding claim 5, the recitation “polyA signal” is inconsistent with the rest of the disclosure. It is recommended to revise it to “poly(A) tail signal” as claimed in claim 1.
Regarding claim 6, the recitation “WPRE” should be spelled out for the first time.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
7. 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.
8. Claims 1-24, 27-29 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.
Claim 1 recites the limitation "the promoter…" in line 5. There is insufficient antecedent basis for this limitation in the claim as this is the first time a promoter is mentioned in the claim.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
Claim Interpretation
9. To advance prosecution, claim 1 is interpreted as reciting “… one or more regulatory elements” comprising a promoter that promotes “expression of the hGALT coding sequence and a polyadenylation (poly(A)) tail signal; the promoter …” and examined on the merit herein. Conversely, claim 5 is interpreted as reciting “the poly(A) tail signal” and examined on the merit accordingly.
Claims 5, 7-12, 15-16, 23-24 recite “has” or “having”, both transitional phrases are interpreted as “comprising” under the Broadest Reasonable Interpretation.
Claim Rejections - 35 USC § 102
10. 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.
11. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 6, 13-15, 17-22, 27-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Loiler (WO2020047472A1, published on 03/05/2020, listed on IDS 02/28/2024).
Regarding claim 1, Loiler (2020) teaches a recombinant adeno-associated virus (AAV) vector comprising an expression cassette (FIGs. 1A-1C), which comprises a nucleotide sequence encoding human galactose-1-phosphate uridylyl transferase (hGALT; FIGs. 1A-1C). Loiler teaches that the sequence encoding hGALT is operably linked to one or more regulatory elements comprising a promoter that promotes expression of the hGALT coding sequence and a polyadenylation (poly(A)) tail signal. Loiler teaches that the promoter may comprises a cytomegalovirus (CMV) early enhancer, chicken ß-actin, rabbit ß-globin splice acceptor (CAG) promoter, or an elongation factor-1 (EF-1) promoter (Page 3, ¶[0009] lines 6 and 9). Loiler teaches that the poly(A) tail signal may comprise a bovine growth hormone (bGH) poly(A) tail signal or a simian virus 40 (SV40) poly(A) tail signal (FIGs. 1A-1C; Page 29, ¶[0117] line 8; Page 46, lines 6). Finally, Loiler teaches that the AAV vector includes flanking inverted terminal repeat (ITR) nucleotide sequences (FIGs. 1A-1C; Page 2, ¶[0007]).
Regarding claim 2, Loiler further teaches that the hGALT protein encoded by the recombinant AAV vector comprises the amino acid sequence in SEQ ID NO: 4, which is a 100% perfect match with the claimed amino acid sequence of instant SEQ ID NO: 1, see alignment below: Query: Loiler (2020) SEQ ID NO: 4, Sbjct: SEQ ID NO: 1 of the instant application.
379/379(100%)
Query 1 MSRSGTDPQQRQQASEADAAAATFRANDHQHIRYNPLQDEWVLVSAHRMKRPWQGQVEPQ 60
MSRSGTDPQQRQQASEADAAAATFRANDHQHIRYNPLQDEWVLVSAHRMKRPWQGQVEPQ
Sbjct 1 MSRSGTDPQQRQQASEADAAAATFRANDHQHIRYNPLQDEWVLVSAHRMKRPWQGQVEPQ 60
Query 61 LLKTVPRHDPLNPLCPGAIRANGEVNPQYDSTFLFDNDFPALQPDAPSPGPSDHPLFQAK 120
LLKTVPRHDPLNPLCPGAIRANGEVNPQYDSTFLFDNDFPALQPDAPSPGPSDHPLFQAK
Sbjct 61 LLKTVPRHDPLNPLCPGAIRANGEVNPQYDSTFLFDNDFPALQPDAPSPGPSDHPLFQAK 120
Query 121 SARGVCKVMCFHPWSDVTLPLMSVPEIRAVVDAWASVTEELGAQYPWVQIFENKGAMMGC 180
SARGVCKVMCFHPWSDVTLPLMSVPEIRAVVDAWASVTEELGAQYPWVQIFENKGAMMGC
Sbjct 121 SARGVCKVMCFHPWSDVTLPLMSVPEIRAVVDAWASVTEELGAQYPWVQIFENKGAMMGC 180
Query 181 SNPHPHCQVWASSFLPDIAQREERSQQAYKSQHGEPLLMEYSRQELLRKERLVLTSEHWL 240
SNPHPHCQVWASSFLPDIAQREERSQQAYKSQHGEPLLMEYSRQELLRKERLVLTSEHWL
Sbjct 181 SNPHPHCQVWASSFLPDIAQREERSQQAYKSQHGEPLLMEYSRQELLRKERLVLTSEHWL 240
Query 241 VLVPFWATWPYQTLLLPRRHVRRLPELTPAERDDLASIMKKLLTKYDNLFETSFPYSMGW 300
VLVPFWATWPYQTLLLPRRHVRRLPELTPAERDDLASIMKKLLTKYDNLFETSFPYSMGW
Sbjct 241 VLVPFWATWPYQTLLLPRRHVRRLPELTPAERDDLASIMKKLLTKYDNLFETSFPYSMGW 300
Query 301 HGAPTGSEAGANWNHWQLHAHYYPPLLRSATVRKFMVGYEMLAQAQRDLTPEQAAERLRA 360
HGAPTGSEAGANWNHWQLHAHYYPPLLRSATVRKFMVGYEMLAQAQRDLTPEQAAERLRA
Sbjct 301 HGAPTGSEAGANWNHWQLHAHYYPPLLRSATVRKFMVGYEMLAQAQRDLTPEQAAERLRA 360
Query 361 LPEVHYHLGQKDRETATIA 379
LPEVHYHLGQKDRETATIA
Sbjct 361 LPEVHYHLGQKDRETATIA 379
Regarding claim 3, Loiler further teaches recombinant AAV vectors comprises the nucleotide sequence that encodes hGALT comprises a nucleic acid SEQ ID NO: 1 having 100% identity to the nucleotide sequence of the instant SEQ ID NO: 2. See alignment below between Query, SEQ ID NO: 1 of Loiler (2020) and Sbjct, SEQ ID NO: 2 of the instant application:
1140/1140(100%)
Query 1 ATGAGCAGAAGCGGCACCGACCCTCAGCAGAGACAGCAGGCCTCTGAAGCCGATGCCGCC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 ATGAGCAGAAGCGGCACCGACCCTCAGCAGAGACAGCAGGCCTCTGAAGCCGATGCCGCC 60
Query 61 GCTGCCACCTTCAGAGCCAATGACCACCAGCACATCCGGTACAACCCCCTGCAGGACGAG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 61 GCTGCCACCTTCAGAGCCAATGACCACCAGCACATCCGGTACAACCCCCTGCAGGACGAG 120
Query 121 TGGGTGCTGGTGTCCGCCCACAGAATGAAGAGGCCTTGGCAGGGCCAGGTGGAACCCCAG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 121 TGGGTGCTGGTGTCCGCCCACAGAATGAAGAGGCCTTGGCAGGGCCAGGTGGAACCCCAG 180
Query 181 CTGCTGAAAACCGTGCCCAGACACGACCCCCTGAACCCTCTGTGTCCTGGCGCCATTAGA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 181 CTGCTGAAAACCGTGCCCAGACACGACCCCCTGAACCCTCTGTGTCCTGGCGCCATTAGA 240
Query 241 GCCAACGGCGAAGTGAACCCCCAGTACGACAGCACCTTCCTGTTCGACAACGACTTCCCC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 241 GCCAACGGCGAAGTGAACCCCCAGTACGACAGCACCTTCCTGTTCGACAACGACTTCCCC 300
Query 301 GCCCTGCAGCCTGATGCCCCATCTCCTGGACCTAGCGACCACCCTCTGTTCCAGGCCAAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 301 GCCCTGCAGCCTGATGCCCCATCTCCTGGACCTAGCGACCACCCTCTGTTCCAGGCCAAG 360
Query 361 TCTGCCAGAGGCGTGTGCAAAGTGATGTGCTTCCACCCTTGGAGCGACGTGACCCTGCCC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 361 TCTGCCAGAGGCGTGTGCAAAGTGATGTGCTTCCACCCTTGGAGCGACGTGACCCTGCCC 420
Query 421 CTGATGAGCGTGCCAGAGATCAGAGCCGTGGTGGATGCCTGGGCCAGCGTGACAGAAGAA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 421 CTGATGAGCGTGCCAGAGATCAGAGCCGTGGTGGATGCCTGGGCCAGCGTGACAGAAGAA 480
Query 481 CTGGGAGCCCAGTACCCCTGGGTGCAGATCTTCGAGAACAAGGGCGCCATGATGGGCTGC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 481 CTGGGAGCCCAGTACCCCTGGGTGCAGATCTTCGAGAACAAGGGCGCCATGATGGGCTGC 540
Query 541 AGCAACCCCCACCCTCACTGTCAAGTGTGGGCCAGCAGCTTCCTGCCCGATATCGCCCAG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 541 AGCAACCCCCACCCTCACTGTCAAGTGTGGGCCAGCAGCTTCCTGCCCGATATCGCCCAG 600
Query 601 CGGGAAGAGAGAAGCCAGCAGGCTTACAAGAGCCAGCACGGCGAGCCCCTGCTGATGGAA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 601 CGGGAAGAGAGAAGCCAGCAGGCTTACAAGAGCCAGCACGGCGAGCCCCTGCTGATGGAA 660
Query 661 TACTCCAGACAGGAACTGCTGCGGAAAGAACGGCTGGTGCTGACCAGCGAGCACTGGCTG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 661 TACTCCAGACAGGAACTGCTGCGGAAAGAACGGCTGGTGCTGACCAGCGAGCACTGGCTG 720
Query 721 GTGCTGGTGCCTTTTTGGGCCACATGGCCCTACCAGACCCTGCTGCTGCCTAGAAGGCAC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 721 GTGCTGGTGCCTTTTTGGGCCACATGGCCCTACCAGACCCTGCTGCTGCCTAGAAGGCAC 780
Query 781 GTGCGGAGACTGCCTGAGCTGACACCCGCCGAGAGAGATGACCTGGCCAGCATCATGAAG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 781 GTGCGGAGACTGCCTGAGCTGACACCCGCCGAGAGAGATGACCTGGCCAGCATCATGAAG 840
Query 841 AAACTGCTGACCAAATACGACAACCTGTTCGAGACCAGCTTCCCCTACAGCATGGGCTGG 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 841 AAACTGCTGACCAAATACGACAACCTGTTCGAGACCAGCTTCCCCTACAGCATGGGCTGG 900
Query 901 CACGGCGCTCCTACAGGATCTGAGGCTGGCGCCAACTGGAACCACTGGCAGCTGCACGCC 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 901 CACGGCGCTCCTACAGGATCTGAGGCTGGCGCCAACTGGAACCACTGGCAGCTGCACGCC 960
Query 961 CACTACTACCCCCCACTGCTGAGATCTGCCACCGTGCGGAAGTTCATGGTGGGATACGAG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 961 CACTACTACCCCCCACTGCTGAGATCTGCCACCGTGCGGAAGTTCATGGTGGGATACGAG 1020
Query 1021 ATGCTGGCTCAGGCCCAGAGAGATCTGACCCCTGAACAGGCCGCCGAACGGCTGAGAGCA 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1021 ATGCTGGCTCAGGCCCAGAGAGATCTGACCCCTGAACAGGCCGCCGAACGGCTGAGAGCA 1080
Query 1081 CTGCCCGAAGTGCACTACCACCTGGGACAGAAGGACAGAGAGACAGCCACAATCGCCTGA 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1081 CTGCCCGAAGTGCACTACCACCTGGGACAGAAGGACAGAGAGACAGCCACAATCGCCTGA 1140
Regarding claim 4, Loiler further teaches that “…a recombinant adeno- associated viral ("AAV") vector comprising… the polynucleotide sequence encoding GALT comprises…the nucleotide sequence set forth in SEQ ID NO: 1” (Page 1, ¶[0005]; FIGs 1A-1C). Since SEQ ID NO: 1 disclosed by Loiler is 100% match with the instant SEQ ID NO: 2, as shown above, the nucleic acid that encodes hGALT in the AAV vectors disclosed by Loiler comprises the sequence set forth in the instant SEQ ID NO: 2.
Regarding claim 6, Loiler further teaches “WPRE” as an additional component of an embodiment for the rAAV vector (Page 3, ¶[0010]).
Regarding claim 13, since the instant specification teaches that “although the scAAV ITR (e.g. SEQ ID NO:13) was developed by mutating or altering a wild type AAV2 ITR (e.g. SEQ ID NO: 11, which is the 5' flanking ITR” (145nt; Page 17, last 2 lines), Loiler further teaches a recombinant self-complementary AAV (scAAV; Page 2, ¶[0006]), comprising an scAAV 3’ ITR having a nucleotide sequence of the instant SEQ ID NO: 13 (106nt). See the alignment below and vector map (FIG 1A).
Query=instant SEQ ID NO: 13; Sbject=Loiler SEQ ID NO: 2.
Query 1 CCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGAC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2436 CCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGAC 2495
Query 61 GCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG 106
||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2496 GCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG 2541
Regarding claim 14, Loiler further teaches recombinant AAV virions comprising: 1) an AAV capsid; and 2) the recombinant AAV vector encompassed by the instant claim 1; and the AAV capsid protein encapsulating the recombinant AAV vector (Page 19, ¶[0085]).
Regarding claim 15, Loiler further teaches recombinant AAV virions, wherein the AAV capsid has an amino acid sequence (SEQ ID NO: 10) which is 85.5% identical to the instant SEQ ID NO: 18 (AAV9 capsid), see alignment below: Query=Loiler SEQ ID NO: 10 Sbjct=Instant SEQ ID NO: 18.
Score
Expect
Identities
Positives
Gaps
1295
0.0
631/738(86%)
672/738(91%)
2/738(0%)
Query 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDNGRGLVLPGYKYLGPFNGLD 60
MAADGYLPDWLEDNLSEGIREWW LKPGAP+PKANQQ QDN RGLVLPGYKYLGP NGLD
Sbjct 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
Query 61 KGEPVNAADAAALEHDKAYDQQLQAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
KGEPVNAADAAALEHDKAYDQQL+AGDNPYL+YNHADAEFQERL+EDTSFGGNLGRAVFQ
Sbjct 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Query 121 AKKRVLEPLGLVESPVKTAPGKKRPVEPSPQRSPDSSTGIGKKGQQPAKKRLNFGQTGDS 180
AKKR+LEPLGLVE KTAPGKKRPVE SPQ PDSS GIGK G QPAKKRLNFGQTGD+
Sbjct 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQE-PDSSAGIGKSGAQPAKKRLNFGQTGDT 179
Query 181 ESVPDPQPIGEPPAGPSGLGSGTMAAGGGAPMADNNEGADGVGSSSGNWHCDSTWLGDRV 240
ESVPDPQPIGEPPA PSG+GS TMA+GGGAP+ADNNEGADGVGSSSGNWHCDS WLGDRV
Sbjct 180 ESVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRV 239
Query 241 ITTSTRTWALPTYNNHLYKQISNGTSGGSTNDNTYFGYSTPWGYFDFNRFHCHFSPRDWQ 300
ITTSTRTWALPTYNNHLYKQISN TSGGS+NDN YFGYSTPWGYFDFNRFHCHFSPRDWQ
Sbjct 240 ITTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQ 299
Query 301 RLINNNWGFRPKRLNFKLFNIQVKEVTQNEGTKTIANNLTSTIQVFTDSEYQLPYVLGSA 360
RLINNNWGFRPKRLNFKLFNIQVKEVT N G KTIANNLTST+QVFTDS+YQLPYVLGSA
Sbjct 300 RLINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSA 359
Query 361 HQGCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFEFSYNFED 420
H+GCLPPFPADVFMIPQYGYLTLN+GSQAVGRSSFYCLEYFPSQMLRTGNNF+FSY FE+
Sbjct 360 HEGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFEN 419
Query 421 VPFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNW 480
VPFHSSYAHSQSLDRLMNPLIDQYLYYLS+T + G Q L FS AGP+NM+ Q +N+
Sbjct 420 VPFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQ-NQQTLKFSVAGPSNMAVQGRNY 478
Query 481 LPGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSS 540
+PGP YRQQRVSTT++QNNNS FAW GA+ + LNGR+SL+NPG AMA+HK+ E+RFFP S
Sbjct 479 IPGPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLS 538
Query 541 GVLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNS 600
G L+FGKQG G+DNVD VM+T+EEEIKTTNPVATE YG VA N Q A G V +
Sbjct 539 GSLIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQN 598
Query 601 QGALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGLKHPPPQILIKNTPVPADP 660
QG LPGMVWQ+RDVYLQGPIWAKIPHTDGNFHPSPLMGGFG+KHPPPQILIKNTPVPADP
Sbjct 599 QGILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADP 658
Query 661 PTTFNQAKLASFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSTNVDFAVNTE 720
PT FN+ KL SFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKS NV+FAVNTE
Sbjct 659 PTAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTE 718
Query 721 GTYSEPRPIGTRYLTRNL 738
G YSEPRPIGTRYLTRNL
Sbjct 719 GVYSEPRPIGTRYLTRNL 736
Regarding claim 17, Loiler further teaches a method in claim 37 (Page 60) for treating galactosemia in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the recombinant AAV virion comprising the recombinant AAV vector described above and the AAV capsid protein encapsulating the recombinant AAV vector as claimed in the instant claim 14.
Regarding claim 18, the recitation “a method of increasing galactose metabolism in a subject” is an intended outcome. There is no additional active step involved to distinguish the claim from the prior art involving a method comprising the same active steps. However, Loiler further teaches “a method of increasing galactose metabolism in a subject that may, in one aspect, be suffering from galactosemia…” (Page 4, ¶[0016]) when describing the claimed invention in claim 37, which is identical to the instant claims 17 and 18 in scope.
Regarding claim 19, Loiler further teaches a method of reducing a disease condition in a subject suffering from galactosemia, the method comprising administering to the subject a therapeutically effective amount of the recombinant AAV virion encompassed by the instant claim 14, “the disease condition comprising jaundice, hepatosplenomegaly, hepatocellular insufficiency, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis, cataract, ataxia, tremor, decreased bone density, or primary ovarian insufficiency” (Page 4, ¶[0017]). The claimed functional limitations are also intended outcomes, with no additional active step that distinguishes from the prior art.
Regarding claim 20, Loiler further teaches “Non-limiting examples of route of administration include intravenous, intra-arterial, intramuscular, intracardiac, intrathecal, subventricular, epidural, intracerebral, intracerebroventricular, sub-retinal, intravitreal, intraarticular, intraocular, intraperitoneal, intrauterine, intradermal, subcutaneous, transdermal, transmuccosal, and inhalation” when discussion examples of administration routes for the claimed recombinant AAV virion (Page 26, ¶[0105]).
Regarding claim 21, Loiler further teaches “… intracardiac, intrathecal, …” when discussion examples of administration routes for the recombinant AAV virion (Page 26, ¶[0105]).
Regarding claim 22, Loiler further teaches several examples of a plasmid comprising 1) an origin of replication (Arrow with “Ori” in FIGs 1B-1C) and 2) the recombinant AAV vector of the instant claim 1.
Regarding claim 27, Loiler further teaches a cell for in vitro packaging and production of the recombinant AAV virions, hence teaches “a cell comprising an AAV vector plasmid” (Page 3, ¶[0013]) of the instant claim 22 “and a second plasmid comprising nucleotide sequences encoding rep and cap; the cap encoding a VP1, a VP2, and a VP3; the rep encoding rep78, rep68, rep52, and rep40” (Page 18, ¶[0082]; Page 20, ¶[0086]).
Regarding claim 28, Loiler further teaches “In some embodiments, the viral capsid protein is a VP1, optionally of AAV9, …” (Page 28, ¶[0105]) and that “The cap gene … encodes the three capsid proteins VP1, VP2, and VP3” (Page 20, ¶[0086]). Hence, Loiler further teaches the cell of instant claim 27, wherein the cap is AAV9 cap.
Regarding claim 29, Loiler further teaches a method of producing an AAV virion, the method comprising culturing a host cell, a packaging cell line (Page 29, ¶[0116]; Page 31, ¶[0122]), comprising the AAV vector plasmid of claims 22, a second plasmid encoding the cap and rep, i.e. helper plasmid (Page 29, ¶[0116]); the cap encoding the VP1, the VP2, and the VP3; the rep encoding rep78, rep68, rep 52, and rep 40 (Page 20, ¶[0086]); and any additional adenoviral helper functions required for AAV replication, under conditions sufficient to produce the AAV virion; and isolating the AAV virion produced by the host cell (Page 31, ¶[0122]).
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Loiler (2020) in view of Wilson (US20230270884A1, published on 08/31/2023, priority on 07/13/2020 in PRO63/051,336)
The teachings of Loiler (2020) have been discussed above and applied herein. Loiler further teaches one embodiment of the claimed recombinant AAV vector (SEQ ID NO: 3; FIG. 1C), wherein the poly(A) tail signal has a nucleotide sequence of the instant SEQ ID NO: 15, see alignment below.
Loiler does not teach the promoter has a nucleotide sequence of SEQ ID NO: 9 or SEQ ID NO: 10.
However, Wilson (2020) teaches an 841nt promoter in SEQ ID NO: 87 (SEQ listing indicates it is a CAG promoter on Page 116), which comprises the claimed instant SEQ ID NO: 9 in its first 670 nucleotide, see alignment below. Wilson further demonstrates that the CAG promoter or its equivalent CB7 promoter with a CMV early enhancer (SEQ ID NO: 86, sharing the same sequence) has been consistently effective for both in vitro and in vivo applications (¶[0025]-[0031]; FIGs 8-12, 14).
Query=instant SEQ ID NO: 9, Sbjct=SEQ ID NO: 87 of Wilson
Query 1 CCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 CCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGA 60
Query 61 CGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCAT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 61 CGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCAT 120
Query 121 ATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 121 ATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCC 180
Query 181 CAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 181 CAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCT 240
Query 241 ATTACCATGGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTccccatctcccccccctcc 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 241 ATTACCATGGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCATCTCCCCCCCCTCC 300
Query 301 ccacccccAattttgtatttatttattttttaattattttGTGCAGCGATgggggcgggg 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 301 CCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTGCAGCGATGGGGGCGGGG 360
Query 361 ggggggggggggcgcgcgccaggcggggcggggcggggcgaggggcggggcggggcgagg 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 361 GGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAGG 420
Query 421 cggagaggtgcggcggcagccaatcagagcggcgcgCTCCGAAAGTTTCCTTTTATggcg 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 421 CGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCG 480
Query 481 aggcggcggcggcggcggccctataaaaagcgaagcgcgcggcgggcgggagtcgctgcg 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 481 AGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTCGCTGCG 540
Query 541 cgctgccttcgccccgtgccccgctccgccgccgcctcgcgccgcccgccccgGCTCTGA 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 541 CGCTGCCTTCGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCCGCCCCGGCTCTGA 600
Query 601 CTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCTGTAAT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 601 CTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCTGTAAT 660
Query 661 TAGCGCTTGG 670
||||||||||
Sbjct 661 TAGCGCTTGG 670
It would have been obvious to persons having ordinary skills in the art (PHOSITAs) before the effective filing date of the claimed invention to have modified the recombinant AAV vector embodiments taught by Loiler via simple substitution of the CAG promoter sequences that had a different sequence design that resulted in different length, taught by Wilson (2020) as one of the preferred embodiments (Page 11, ¶[0074]). It would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to do so because Wilson (2020) teaches that the recombinant AAV vectors comprising the claimed promoter show robust in vitro (FIGs. 8-12) and in vivo gene expression and toxicology profiles in mice (FIG. 14) mediated by a CAG or CB7 promoter with identical sequences (SEQ ID NOs: 86 and 87; ¶[0025]-[0031]).
Claims 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Loiler (2020) in view of Hou (US20200377887A1, published on 12/03/2020, PCT filed on 09/21/2018), further in view of Sahenk (US20200339960A1, published on 10/29/2020, PCT filed on 10/19/2018).
The teachings of Loiler (2020) have been discussed above and applied herein.
Loiler further teaches that the rAAV vector is a self-complementary vector (scAAV) or a single stranded DNA vector (ssAAV) (Page 27, ¶[0107] & [0108]). Loiler teaches that while ssAAVs require second strand synthesis, which limits transfection efficiency, scAAVs show increased and prolonged transgene expression in vitro and in vivo (Page 2, ¶[0007]). Hou further teaches that scAAV viral genomes contain DNA strands which anneal together to form double stranded DNA. By skipping second strand synthesis, scAAVs allow for rapid expression in the cell (Page 8, ¶[0050]). However, the self-anneal requirement for scAAV genomes indicates that the capacity of the scAAV is effectively halved compared with the capacity of ssAAV counterparts. Loiler further teaches good in vivo expression profiles (Loiler, Pages 52-53, Examples 3-5, FIGs. 16-28).
Regarding claim 7, Loiler does not teach any embodiment of the claimed recombinant AAV, wherein the inverted terminal repeat (ITR) nucleotide sequences comprise a 5’ AAV2 ITR having a nucleotide sequence of the instant SEQ ID NO: 11 and a 3’ AAV2 ITR having a nucleotide sequence of the instant SEQ ID NO: 12, or the reverse complement thereof.
However, Hou (2020) teaches at least one embodiment of recombinant AAV vectors, set forth in SEQ ID NO: 45, that meet the above claimed limitations and comprise a 5’ AAV2 ITR having a nucleotide sequence of the instant SEQ ID NO: 11 and a 3’ AAV2 ITR having a nucleotide sequence of the instant SEQ ID NO: 12, or the reverse complement thereof. See alignments below. Hou further teaches good in vivo expression profile (Page 134, Example 4).
Query = The instant SEQ ID NO: 11, Sbjct = Hou SEQ ID NO: 45
Query 1 TTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 TTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGG 60
Query 61 CGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 61 CGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTG 120
Query 121 GCCAACTCCATCACTAGGGGTTCCT 145
|||||||||||||||||||||||||
Sbjct 121 GCCAACTCCATCACTAGGGGTTCCT 145
Query = The instant SEQ ID NO: 12, Sbjct = Hou SEQ ID NO: 45
Query 1 AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4460 AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGG 4519
Query 61 CCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4520 CCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGC 4579
Query 121 GAGCGCGCAGAGAGGGAGTGGCCAA 145
|||||||||||||||||||||||||
Sbjct 4580 GAGCGCGCAGAGAGGGAGTGGCCAA 4604
Regarding claim 8, Loiler does not teach any embodiment of the claimed recombinant AAV, wherein the ITR nucleotide sequences comprise a 5’ AAV2 ITR having a nucleotide sequence of the instant SEQ ID NO: 11 and a 3’ AAV2 ITR having a nucleotide sequence of the instant SEQ ID NO: 13, or the reverse complement thereof.
However, Sahenk (2020) teaches at least one embodiment of recombinant AAV vectors, set forth in SEQ ID NO: 11, that meet the above claimed limitations and comprises a 5’ AAV2 ITR having a nucleotide sequence of the instant SEQ ID NO: 11 and a 3’ AAV2 ITR having a nucleotide sequence of the instant SEQ ID NO: 13, or the reverse complement thereof. See alignments below. Sahenk further teaches good tolerance of scAAV vectors in vivo (Page 96, ¶[0305]) and good in vivo expression (Page 96, ¶[0305]).
Query = The instant SEQ ID NO: 11, Sbjct = Sahenk SEQ ID NO: 11
Query 18 GCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTTGG 77
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2248 GCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTTGG 2189
Query 78 TCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAG 137
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2188 TCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAG 2129
Query 138 GGGTTCCT 145
||||||||
Sbjct 2128 GGGTTCCT 2121
Query = The instant SEQ ID NO: 13, Sbjct = Sahenk SEQ ID NO: 11
Query 1 CCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGAC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 112 CCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGAC 53
Query 61 GCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG 106
||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 52 GCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG 7
It would have been obvious to PHOSITAs before the effective filing date of the claimed invention to have modified the recombinant AAV vector embodiments taught by Loiler via simple substitution of the ITR sequences and would have experimented with different AAV genome types, such as ssAAV and scAAV vectors, to have weighed the pros and cons of each format using the known ITR sequence pairing, involving the claimed SEQ ID NOs: 11, 12, 13, so that optimal transgene expression can be achieved through proven vector structural element arrangements in the art. It would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results because success demonstrated by prior arts. One would have been motivated to do so because the recombinant AAV vectors comprising the claimed ITR pairings show good in vivo gene expression and toxicology profiles. The larger cargo capacity but less efficient ssAAV would have been weighed against the faster and more durable gene expression of scAAVs with smaller cargo capacity, and PHOSITAs would have arrived at the claimed inventions simply by testing and comparing the known formats.
Claims 9-10, 24 are rejected under 35 U.S.C. 103 as being unpatentable over Loiler (2020) in view of Hou (2020), further in view of Derosa (US20160151409A1, published on 06/02/2016), Baltes (US20200140893A1, published on 05/07/2020), Huelsmann (US20140370547A1, published on 12/18/2014), and Azzouz (US20230109504A1, published on 04/06/2023, priority on 04/09/2020 in GB2005321.1).
The teachings of Loiler (2020), and Hou (2020) have been discussed above and applied herein. Loiler further teaches a WPRE sequence that has only 2 mismatches with the claimed WPRE sequence (SEQ ID NO: 14), see alignment below.
Query = The instant SEQ ID NO: 14, Sbjct = Loiler SEQ ID NO: 3
Score Expect Identities Gaps Strand
1077 bits(583) 0.0 587/589(99%) 0/589(0%) Plus/Plus
Query 1 AATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2403 AATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCT 2462
Query 61 CCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2463 CCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGT 2522
Query 121 ATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTAGCTGTCTCTTTATGAGGAGTTG 180
||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||
Sbjct 2523 ATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTG 2582
Query 181 TGGCCCGTTGTCAGGCAACGTGGCGTAGTGTGCACTGTGTTTGCTGACGCAACCCCCACT 240
|||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||
Sbjct 2583 TGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACT 2642
Query 241 GGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2643 GGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCT 2702
Query 301 ATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2703 ATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTG 2762
Query 361 TTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2763 TTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTC 2822
Query 421 GCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2823 GCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC 2882
Query 481 AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2883 AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTT 2942
Query 541 CGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGC 589
|||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2943 CGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGC 2991
Loiler does not teach a rAAV vector, wherein the expression cassette and flanking ITR nucleotide sequences comprise a nucleic acid that has at least 85% identity to the nucleotide sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, or a sequence reverse complementary thereto, and encodes a human GALT.
Nor does Loiler teach a rAAV vector, wherein the expression cassette comprises a nucleic acid that has at least 85% identity to the nucleotide sequence of SEQ ID NO: 19, SEQ ID NO: 20, or SEQ ID NO: 21, or a sequence reverse complementary thereto, and encodes a human GALT.
Loiler also does not teach a plasmid of claim 22, comprising a nucleic acid having at least 85% identity to the nucleotide sequence of SEQ ID NO: 6, SEQ ID NO: 7 or SEQ ID NO: 8, which encodes a human GALT or comprising the nucleotide sequence of SEO ID NO: 6, SEO ID NO: 7, or SEQ ID NO: 8.
However, Hou (2020), Baltes (2020), Derosa (2016), Huelsmann (2014), and Azzouz (2020) each teaches different claimed AAV vector or plasmid elemental sequences based on sequence alignment analysis outcome below (see the attached NCBI_Sequence_Alignment_2026.pdf for alignment details, listed in PTO-892):
-Hou teaches a sequence set forth in SEQ ID NO: 45 that comprises the instant SEQ ID NOs: 11 & 12.
-Loiler teaches a sequence set forth in SEQ ID NO: 3 that comprises 99.7% sequence identity, except 2 mismatches, see alignment above, at positions 158 and 207 of the instant SEQ ID NO: 14.
-Baltes teaches a sequence set forth in SEQ ID NO: 4 that comprises the instant SEQ ID NO: 10.
-Huelsmann teaches a sequence set forth in SEQ ID NO: 9 that comprises the instant SEQ ID NO: 15.
-Derosa teaches a sequence set forth in SEQ ID NO: 2 that comprises an altered hGALT coding sequence in SEQ ID NOs: 21, 5, and 8, which is more stable than the wildtype (Page 43, ¶[0091]).
-Azzouz teaches a plasmid sequence set forth in SEQ ID NO: 22 that comprises the backbone portion of the claimed plasmid with the instant SEQ ID NOs: 6-8. See Prior_Art_Alignment_2026.pdf in PTO-892 for alignment details regarding the element sequences taught by the cited prior art.
The following schema show the arrangements with claimed elements within SEQ ID NOs: 21, 5, 8:
SEQ ID NO: 21 3296/3360x100%=98.1% 3296nt are known elements in the art.
[EF1α promoter]-[hGALT optimized codons]-[ WPRE ]-[bGH poly(A) tail signal]
[SEQ ID NO: 10]-[ ]-[SEQ ID NO: 14]-[ SEQ ID NO: 15 ]
[ Baltes ]-[ Derosa ]-[ Loiler ]-[ Huelsmann ]
[ 167-1348 ]-18-[ 1355 - 2494 ]-23-[ 2516-3104 ]-23-[ 3136 - 3360 ]
SEQ ID NO: 5 3374/3543x100%=95.2% 3374nt are known elements in the art.
[ 5'ITR ]-[ Expression Cassette ]-[ 3' ITR ]-
[SEQ ID NO: 11]-[ SEQ ID NO: 21 ]-[SEQ ID NO: 12]-
[ Hou ]-[ Baltes, Derosa, Loiler, Huelsmann ]-[ Hou ]-
[1-145]-23-[167-1348]-18-[1355-2494]-23-[2516-3104]-23-[3136-3360]-66-[ 3423-3528 ]-16
SEQ ID NO: 8 5945/6230x100%=95.4% 5945nt are known elements in the art.
[ 5' backbone ]-[Expression Cassette & Flanking ITRs]-[ 3' backbone ]
[ ]-[ SEQ ID NO: 5 ]-[ ]
[ Azzouz ]-[Hou, Baltes, Derosa, Loiler, Huelsmann]-[ Azzouz ]
[ 1-395 ]-60-[ 455-3997 ]-56-[ 4053-6230 ]
As over 95% of the sequence of each of the claimed SEQ ID NOs: 21, 5, and 8 comprises known sequences for functional AAV vector elements in the art with only a small fraction (<5%) of the sequences being generic spacers or linkers that function as “glue” resulting from routine laboratory optimization. The prior arts, Hou, Baltes, Derosa, Loiler, Huelsmann, and Azzouz, each teaches various modular element(s) essential for the claimed inventions.
It would have been obvious to PHOSITAs before the effective filing date of the claimed invention to have modified the recombinant AAV vector embodiments taught by Loiler via simple substitution of the known AAV regulatory element sequences and the more stable codon optimized hGALT coding sequences for improved hGALT expression, and would have experimented with different AAV vector elemental architecture known in the art based on the teachings and examples of Hou, Baltes, Derosa, Loiler, Huelsmann, and Azzouz, such that optimal transgene expression can be achieved. It would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to do so because the recombinant AAV vectors comprising the claimed vector elements show good in vivo gene expression and toxicology profiles (Loiler, Pages 52-53, Examples 3-5, FIGs. 16-28; Hou, Page 134, Example 4; Azzouz, Pages 35-39, Examples 2-3). PHOSITAs would have arrived as the claimed inventions through routine optimizations and explorations with reasonable expectation of success.
Regarding claim 9, PHOSITAs would have generated a rAAV vector wherein the expression cassette and flanking ITR nucleotide sequences comprise a nucleic acid that has at least 85% identity to the nucleotide sequence of SEQ ID NO: 5, or a sequence reverse complementary thereto, and encodes a human GALT, and would have tested it with reasonable expectation of success.
Regarding claim 10, PHOSITAs would have generated a rAAV vector wherein the expression cassette comprises a nucleic acid that has at least 85% identity to the nucleotide sequence of SEQ ID NO.: 21, or a sequence reverse complementary thereto, and encodes a human GALT, and would have tested it with reasonable expectation of success.
Regarding claim 24, PHOSITAs would have generated a rAAV plasmid wherein the comprising a nucleic acid having at least 85% identity to the nucleotide sequence of SEQ ID NO: 21, which encodes a human GALT or comprising the nucleotide sequence of SEQ ID NO: 21, and would have tested it with reasonable expectation of success.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Loiler (2020) in view of Asokan (US20140056854A1, published on 02/27/2014).
The teachings of Loiler (2020) have been discussed above and applied herein.
Loiler does not teach a rAAV virion of claim 15, wherein the AAV capsid comprises an amino acid sequence of SEQ ID NO: 18.
However, Asokan (2014) teaches an AAV9 capsid protein set forth in SEQ ID NO: 1 that has 100% match with the claimed AAV9 capsid sequence in SEQ ID NO: 18, and numerous mutated variants thereof (e.g. claim 1). Asokan further teaches that AAV9 vectors display a systemic, multi- organ transduction profile following intravenous administration (Page 1, line 27), and that a wide range of clinically relevant applications benefit from vector targeting to specific tissues rather than multi-organ gene expression (Page 2, lines 1-2), hence providing motivation to explore AAV9 capsid variants.
It would have been obvious to PHOSITAs before the effective filing date of the claimed invention to have modified the recombinant AAV virion embodiments taught by Loiler via simple substitution of the known AAV capsid sequences, and would have experimented with different AAV capsid variants to identify the optimal variant for tissue or cell type specific targeting based on the teachings and examples of Asokan. It would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to do so because the recombinant AAV virions comprising the claimed capsid protein sequence can serve as a baseline control for capsid optimization in identifying a more effective capsid variant that helps to achieve optimal rAAV gene transfection in the intended target tissue types based on the success of Asokan in identifying functional variants that show tissue-specific targeting potential (Page 65 line 9-Page 66 line 29). PHOSITAs would have arrived as the claimed inventions through the explorations.
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.
US Application 18/688,724
Claims 1-24, 27-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 7, 9, 12, 14, 16, 18, 20-21, 23-28, 31-36 and 39 of copending Application 18/688,724. Although the claims at issue are not identical, they are not patentably distinct from each other.
US Application 18/688,724 teaches a composition of AAV capsid and recombinant AAV vectors comprising regulatory elements and a nucleic acid sequence encoding the human GALT gene and methods of treating galactosemia using the claimed composition with a plurality of intended outcomes.
Regarding claims 1 & 14, claim 1 of US Application 18/688,724 teaches all limitations.
Regarding claims 2-4, claims 20 and 21 of US Application 18/688,724 teach all sequence limitations for the hGALT transgene encoded by the rAAV vectors.
Regarding claim 5, claim 23 of US Application 18/688,724 teaches all sequence limitations.
Regarding claim 6, claim 24 of US Application 18/688,724 teaches the same WPRE limitation.
Regarding claims 7 & 8, claims 25 and 26 of US Application 18/688,724 teach the same ITR sequences of the instant claims.
Regarding claims 9 & 11, claim 27 of US Application 18/688,724 teaches the same sequence.
Regarding claims 10 & 12, claim 28 of US Application 18/688,724 teaches the same sequence.
Regarding claim 13, claim 31 of US Application 18/688,724 teaches the same AAV types.
Regarding claims 15 & 16, claims 32 & 33 of US Application 18/688,724 teaches the same AAV capsid amino acid sequence.
Regarding claims 17-19, claims 3-4, 7-9, 12, 14, 16, 18 of US Application 18/688,724 teaches the same method of treating galactosemia.
Regarding claims 20 & 21, claims 34 & 35 of US Application 18/688,724 teaches the same administration routes.
Regarding claim 24, claim 28 of US Application 18/688,724 teaches the same sequence.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
US Application 18/715,015
Claims 1-24, 27-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-9, 11-12, 14-17, 19-20, 23-24, 26 and 28 of copending Application 18/688,724 in view of Loiler (2020), further in view of Derosa (2016), see full citation above. Although the claims at issue are not identical, they are not patentably distinct from each other.
US Application 18/715,015 teaches a recombinant AAV vector encoding a hPax4 gene and methods for treating diabetes mellitus in a subject in need thereof or methods for reducing the risk of developing diabetes in a subject positive for anti-islet auto-antibodies, methods comprising administering a therapeutically effective amount of AAV virions to the subject in need thereof, and involve rAAV vectors, expression cassettes, and plasmids comprising modular regulatory elements, along with a method of producing rAAV virions.
US Application 18/715,015 does not teach a rAAV encoding hGALT gene for treating galactosemia.
However, Loiler (2020) and Derosa (2016) teaches using a rAAV vector comprising different nucleic acid sequences encoding the same human GALT and an AAV capsid to treat galactosemia.
It would have been obvious to PHOSITAs before the effective filing date of the claimed invention to have modified the recombinant AAV virion embodiments taught by Loiler and Derosa via simple substitution of the known AAV capsid sequences disclosed in US Application 18/715,015, and would have experimented with different AAV vector designs, regulatory element or capsid variants to identify the optimal variant for optimal vector performance and therapeutic outcomes based on the teachings and examples of the US Application 18/715,015. It would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to do so because of the in vivo impact of the rAAV vectors demonstrated by US Application 18/715,015 (Page 12, ¶[0069] & [0070]; FIG. 5 & FIG. 6). PHOSITAs would have arrived at the claimed inventions through the explorations with reasonable expectation for success.
Claims 1, 7-9, 11-12, 24 of the US Application 18/715,015 correspond to the instant claims 1, 5, 7-16, 22-24.
Claims 14-17, 19-20, 23 of the US Application 18/715,015 correspond to the instant claims 17-21.
Claim 26 of the US Application 18/715,015 correspond to the instant claims 27-28.
Claim 28 of the US Application 18/715,015 correspond to the instant claims 29.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 11-12, 23 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
1). The claimed sequences set forth in SEQ ID NOs: 3 (claim 11), 19 (claim 12), and 6 (claim 23) are free of prior art based on sequence search. The closest prior art sequence match for SEQ ID NO: 3 (claim 11) is at 71%, 82.7% for SEQ ID NO: 19 (claim 12), and 52.5% for SEQ ID NO: 6 (claim 23) based on sequence search. Hence, nothing in the art teaches sequencing having any of SEQ ID NOs: 3, 19, or 6.
The modular sequence analysis performed above also indicates that, despite the teachings of modular elemental sequences for AAV vector design in the art, there is no obvious teaching for PHOSITAs to combine the known elements in a specific fashion to arrive at the sequences set forth in SEQ ID NOs: 3, 19, and 6, particularly due to the inclusion of the truncated CAG promoter variant set forth in SEQ ID NO: 9, as its closest prior art based on sequence search, Wilson (2020), discloses an 841nt CAG promoter sequence (SEQ ID NO: 87) that comprises the 670nt sequence of SEQ ID NO: 9, but there is no teaching in the art that specifically directs PHOSITAs to make the specific truncation to be able to insert SEQ ID NO: 9 of the instant disclosure in the claimed SEQ ID NOs: 3 (claim 11), 19 (claim 12), and 6 (claim 23). Hence, it is not obvious for PHOSITAs to arrive at these claimed sequences via routine optimization.
2). The claimed SEQ ID NOs: 4 (claim 11), 20 (claim 12), and 7 (claim 23) are free of prior art based on sequence search. The closest prior art sequence match for SEQ ID NO: 4 (claim 11) is at 59.5%, 76.2% for SEQ ID NO: 20 (claim 12), and 53% for SEQ ID NO: 7 (claim 23) based on sequence search. Hence, nothing in the art teaches sequencing having any of SEQ ID NOs: 4, 20, or 7.
SEQ ID NOs: 4 (claim 11), 20 (claim 12), and 7 (claim 23) all contain a 666nt CAG variant promoter that partially aligns with the SEQ ID NO: 9, see alignment below. Although this promoter also has a closely related art that teaches a 1614nt CAG promoter variant that encompasses the entire 666nt variant sequence, e.g. Pauza (US20170335344A1, published on 11/23/2017) teaches a 1614nt CAG promoter variant set forth in SEQ ID NO: 36. Hence, the 666nt CAG promoter variant is free of prior art based on sequence search, and it requires specific truncation of the known closest counterpart in the art, i.e. a 1614nt variant, in order to fit into the SEQ ID NOs: 4, 7, and 20. There is no obvious teaching for PHOSITAs to combine the known elements in a specific fashion to arrive at the sequences set forth in SEQ ID NOs: 4, 7, and 20 via routine optimization.
Query = Instant SEQ ID NO: 9, Sbjct = Instant SEQ ID NO: 4
Query 1 CCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 278 CCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGA 337
Query 61 CGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCAT 120
|||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||
Sbjct 338 CGTCAATGGGTGGACTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCAT 397
Query 121 ATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 398 ATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCC 457
Query 181 CAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 458 CAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCT 517
Query 241 ATTACCAT-GGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTccccatctcccccccctc 299
|||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 518 ATTACCATGGGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCATCTCCCCCCCCTC 577
Query 300 cccacccccAattttgtatttatttattttttaattattttGTGCAGCGATgggggcggg 359
||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |
Sbjct 578 CCCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTGCAGCGATGGGGGC--G 635
Query 360 gggggggggggggcgcgcgccaggcggggcggggcggggcgaggggcggggcggggcgag 419
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 636 GGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAG 695
Query 420 gcggagaggtgcggcggcagccaatcagagcggcgcgCTCCGAAAGTTTCCTTTTATggc 479
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 696 GCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGC 755
Query 480 gaggcggcggcggcggcggccctataaaaagcgaagcgcgcggcgggcgggagtcgctgc 539
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 756 GAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTCGCTGC 815
Query 540 gcgctgccttcgccccgtgccccgctccgccgccgcctcgcgccgcccgccccgGCTCTG 599
| ||||||||||||||||||||||||| ||||||||||||||||||||||||||||||
Sbjct 816 GT--TGCCTTCGCCCCGTGCCCCGCTCCG-CGCCGCCTCGCGCCGCCCGCCCCGGCTCTG 872
Query 600 ACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCTGTAA 659
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 873 ACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCTGTAA 932
Query 660 TTAGCGCTTGG 670
|||||||||||
Sbjct 933 TTAGCGCTTGG 943
3). The claimed SEQ ID NOs: 5 (claim 11), 21 (claim 12), and 8 (claim 23) are free of prior art based on sequence search. The closest prior art sequence match for SEQ ID NO: 5 (claim 11) is at 51.9%, 53.1% for SEQ ID NO: 21 (claim 12), and 51.2% for SEQ ID NO: 8 (claim 23) based on sequence search. Hence, nothing in the art teaches sequencing having any of SEQ ID NOs: 5, 21, or 8.
The claimed SEQ ID NOs: 5 (claim 11), 21 (claim 12), and 8 (claim 23), all comprising a 589nt WPRE variant sequence set forth in the claimed SEQ ID NO: 14, which is free of prior art based on sequence search. The closest prior art teaches a 589nt WPRE variant with 99.5 sequence identity similarity, e.g. SEQ ID NO: 5 from Shen (US20190373868A1, published on 12/12/2019) teaches a 589nt WPRE variant sequence, which as shown below, has only two mismatch positions at positions 158 and 207. However, Choi (Mol Brain. 2014 Mar 11;7:17) teaches a 247nt miniature WPRE variant called WPRE3, which was created by fusing only the minimal gamma (1-158nt) and minimal alpha (80nt) components of a tripartite WPRE sequence (alpha, beta, and gamma; Page 2, 4th ¶), and it can maintain an approximately 83% activity (Page 5, last 2 lines; Page 6, left column, first 2 lines). Based on the teachings of the minimal 80nt alpha and 158nt gamma components by Donello (Virol. 1998 Jun;72(6):5085-92; Page 5088, Figure 3A; Page 5089, Figure 4A; Page 5090, Figure 5A & 5B) and the WPRE sequence in Genbank (Genbank_1993_J04514_Woodchuck hepatitis B virus in PTO-892 form), PHOSITAs could generate additional variants. However, since one of the two mutations occurs at position 158, the last position of the 158nt minimal gamma component, which was not taught by Choi or Donello, it is thus not obvious that OSITA would arrive at this position.
Query = Shen SEQ ID NO: 5, Sbjct = Instant SEQ ID NO: 14
Alignment statistics for match #1
Score Expect Identities Gaps Strand
1077 bits(583) 0.0 587/589(99%) 0/589(0%) Plus/Plus
Query 1 AATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 AATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCT 60
Query 61 CCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 61 CCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGT 120
Query 121 ATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTG 180
||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||
Sbjct 121 ATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTAGCTGTCTCTTTATGAGGAGTTG 180
Query 181 TGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACT 240
|||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||
Sbjct 181 TGGCCCGTTGTCAGGCAACGTGGCGTAGTGTGCACTGTGTTTGCTGACGCAACCCCCACT 240
Query 241 GGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 241 GGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCT 300
Query 301 ATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 301 ATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTG 360
Query 361 TTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 361 TTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTC 420
Query 421 GCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 421 GCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC 480
Query 481 AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 481 AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTT 540
Query 541 CGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGC 589
|||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 541 CGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGC 589
Hence, it is not obvious for PHOSITAs to arrive at claimed these sequences via routine laboratory optimization and simple combination of known AAV vector elements.
Thus, sequences set forth in the instant SEQ ID NOs: 3-8 and 19-21 are free of prior art and claims 11, 12, 23 would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Subject Matter Eligibility Analysis
Regarding claim 27, the recitation “a cell” does not read on human organism because the specification does not teach either administering the AAV plasmid to a subject or the cell as claimed to a subject. There are references to “culturing a host cell”, or “a packaging cell line” when describing AAV virion packaging or production (Page 7, embodiment 29; Page 27, 2nd¶).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Delphinus D. Yu whose telephone number (571) 272-1576. The examiner can normally be reached Mon-Thr 7:30am to 4:30pm Fri 10am to 2pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil P Hammell can be reached on (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DELPHINUS DOU YI YU/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights