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 election without traverse of 1) Group I, drawn to claims 16-32, and 2) species of SEQ ID NO: 5 (claim 24), in the reply filed on 01/09/2026 is acknowledged. The sequence set forth in SEQ ID NO: 5 appears to be free of the art, and therefore, search has been extended to SEQ ID NOs: 21, 23, 25, 27, 29, 31, 33, 35 and 37 enumerated in claim 24. Claims 33-35 are withdrawn from further consideration as being drawn to a non-elected invention.
Priority
The instant application is a 371 of PCT/EP2021/074964 filed 09/10/2021, which claims priority to European Patent Office (EPO) 20306005.8 filed 09/10/2020.
Claim Objections
Claims 16-18 and 24 are objected to because of the following informalities:
Claim 16 recites the phrase “ends of SEQ ID NO: 1” (line 5), which should be corrected to “ends of the sequence set forth in SEQ ID NO: 1” because SEQ ID NO: 1 is a sequence identifier, not a sequence per se.
Claim 17 has a semicolon between N and T (line 2), which is presumed to be a typographical error for a comma.
Claims 18 and 24 are objected to for the same reason as set forth above for claim 16.
Appropriate correction is required.
Claim Interpretation
Claim 1 recites the limitation “small amino-acids” (line 5). The specification recites, “Small amino acids have a lateral chain with a small steric hindrance, generally chosen from H, or a Cl-C2 alkyl group that may be substituted with one or more of methyl, carboxyl, hydroxyl and/or amine groups” (p 9, para 45). This definition is used for the purposes of examination.
Claim 18 recites the limitation “wherein the sequence of small amino- acids consists of” (lines 1-2). The phrase “consists of” is interpreted as referring to the Markush groups of amino acid residues at the N-terminal and C-terminal ends of SEQ ID NO: 1 (i.e., “wherein the sequence of small amino acids is selected from the group consisting of”).
Claim Rejections - 35 USC § 112(b)
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 17, 21, 23, and 25 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 17 recites the limitation “wherein the sequence of small amino- acids consists of up to five amino acids” (lines 1-2). It is unclear whether the limitation “up to five amino acids” refers to the total combined number of small amino acids at the N-terminal and C-terminal ends, or whether it refers to the upper limit of small amino acids at each of the N-terminal and C-terminal ends. The second interpretation is the broadest reasonable interpretation of this phrase, and is therefore used for the purpose of examination.
Claim 21, which depends from claim 16, recites the limitation “wherein the insertion site is at a position selected from positions 587, 588, 589, 453, 520, 584 and 585” (lines 1-2). Claim 16 recites that the AAV capsid protein comprises “a muscle-targeting peptide insertion between two consecutive amino acids of the capsid protein sequence” (lines 2-3, emphasis added). This implies that the location of the peptide insertion must be identified by the positions of two residues. In claim 21, it is unclear whether “the insertion site is at a position” means that the insertion site is before a position (e.g., before position 587, such that the insertion is between position 586 and 587) or after a position (e.g., after position 587, such that the insertion is between position 587 and 588).
Claim 23 recites the limitation “insertion at position 598” (line 2), which is indefinite for the same reason as set forth above for claim 21.
Claim 25 recites the limitation “the sequences having at least 85%, 87%, 88%, 90%, 95%, 97%, 98% or 99% identity with said sequence” (lines 2-3). It is unclear whether “said sequence” refers to the sequence set forth in SEQ ID NO: 6 (line 2 of claim 25) or to the sequence set forth in SEQ ID NO: 1 (liens 4-5 of claim 1). For the purpose of examination, this limitation in claim 25 is interpreted as “the sequences having at least 85%, 87%, 88%, 90%, 95%, 97%, 98% or 99% identity with the sequence set forth in SEQ ID NO: 6.”
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 25 and 28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
From M.P.E.P. § 2163, the analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated possession of the claimed invention from the standpoint of one of skill in the art at the time the application was filed. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.
For claims drawn to a genus, possession may be shown (for example) through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus, and is an inverse function of the skill and knowledge in the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, para. 1.
Claim 25 is drawn to the modified AAV capsid protein of claim 23, which comprises a sequence selected from the group consisting of the sequence SEQ ID NO: 6 and the sequences having at least 85%, 87%, 88%, 90%, 95%, 97%, 98% or 99% identity with said sequence. Claim 23, in turn, is drawn to the modified AAV capsid protein of claim 16, which is from AAV9.rh74 and comprises the muscle-targeting peptide insertion at position 589, according to the numbering in AAV2 capsid protein sequence. Claim 16, in turn, is drawn to a modified AAV capsid protein comprising a muscle-targeting peptide insertion between two consecutive amino acids of the capsid protein sequence and without any modification of the capsid protein amino acid sequence upstream and downstream of the insertion site, wherein the targeting peptide comprises the sequence SEQ ID NO: 1 and a sequence of small amino-acids at the N-terminal and C-terminal ends of SEQ ID NO: 1.
Claim 28 is drawn to the polynucleotide according to claim 27, which comprises the sequence SEQ ID NO: 7 or a sequence having at least 80%, 85%, 90%, 95%, 97%, 98% or 99% identity with said sequence. Claim 27, in turn, is drawn to a polynucleotide encoding the modified AAV capsid protein according to claim 16.
Claims 25 and 28 recite a structure: the modified AAV capsid protein of claim 23, which comprises a sequence selected from the group consisting of the sequence SEQ ID NO: 6 and the sequences having at least 85%, 87%, 88%, 90%, 95%, 97%, 98% or 99% identity with said sequence (claim 25), or the polynucleotide according to claim 27, which comprises the sequence SEQ ID NO: 7 or a sequence having at least 80%, 85%, 90%, 95%, 97%, 98% or 99% identity with said sequence (claim 28). Claims 25 and 28 also recite a function: wherein the peptide insertion in the AAV capsid protein is a muscle-targeting peptide. Thus, the claims are each drawn to a product comprising a very large genus of a modified AAV capsid protein (claim 25) or a polynucleotide (claim 28) comprising the claimed function.
Neither the specification nor the prior art establishes a structure-function relationship wherein a modified AAV capsid protein of claim 23, which comprises a sequence selected from the group consisting of the sequence SEQ ID NO: 6 and the sequences having at least 85%, 87%, 88%, 90%, 95%, 97%, 98% or 99% identity with said sequence (claim 25), or a polynucleotide according to claim 27, which comprises the sequence SEQ ID NO: 7 or a sequence having at least 80%, 85%, 90%, 95%, 97%, 98% or 99% identity with said sequence, would be capable of functioning as claimed with any degree of predictability.
The instant specification appears to only have one modified AAV capsid protein capable of functioning as claimed according to claim 25: the full sequence as set forth in SEQ ID NO: 6 (para 134). The amino acid sequence set forth in SEQ ID NO: 6 consists of 749 residues. The specification does not disclose any other embodiments which would be encompassed within the pending claim. Likewise, the instant specification appears to only have one polynucleotide capable of functioning as claimed according to claim 28: the full sequence as set forth in SEQ ID NO: 7 (para 134). The sequence set forth in SEQ ID NO: 7 consists of 2250 nucleotide bases. The specification does not identify what changes, mutations, fragments, etc. could be made to SEQ ID NOs: 6 or 7, and that would be encompassed by the structural limitations of claims 25 or 28, and would predictably result in the claimed function of the peptide insertion being a muscle-targeting peptide. As such, the instant specification does not provide a sufficient representative sampling of structures that are as little as 85% identical to the sequence set forth in SEQ ID NO: 6 (claim 25) or as little as 80% identical to the sequence set forth in SEQ ID NO: 7 (claim 28) that are capable of providing for said function as claimed.
The prior art is unpredictable. The sequence set forth in SEQ ID NO: 6 is the amino acid sequence of the AAV9-rh-74-HB-P1 capsid protein (para 55, 135). The sequence set forth in SEQ ID NO: 7 is the nucleotide sequence encoding the polypeptide sequence set forth in SEQ ID NO: 6 (para 55, 135). WO2019/193119 discloses a hybrid AAV9.rh74 capsid, which has tropism for muscle cells and tissues (Abstract; p 3, line 1 – p 4, line 14). However, WO2019/193119 does not teach what modifications may be made to the AAV9.rh74 capsid, such that the capsid retains its muscle tropism. Thus, the prior art cannot be relied upon for making up for the deficit of the instant specification with regard to a sufficient representative number of species that are as little as 85% identical to the sequence set forth in SEQ ID NO: 6 (claim 25) or as little as 80% identical to the sequence set forth in SEQ ID NO: 7 (claim 28) that provide for said function as claimed.
Accordingly, neither the specification nor the prior art establishes a known structure-function relationship wherein the genus of structures that are as little as 85% identical to the sequence set forth in SEQ ID NO: 6 (claim 25) or as little as 80% identical to the sequence set forth in SEQ ID NO: 7 (claim 28) are capable of providing for the function as claimed with any predictability. In this case, the skilled artisan would not have reasonable concluded at the time of the invention that application was in possession of the invention as claimed.
Claim Rejections - 35 USC § 102
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 16-22, 26-27, and 29-32 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Pechan (US 2024/0261437 A1).
Pechan teaches a modified AAV capsid polypeptide comprising an insertion of a polypeptide sequence, wherein the AAV capsid enables preferential targeted expression of a gene of interest in muscle tissues (Abstract; para 5) (claim 16). The modified AAV capsid protein taught in Pechan does not comprise any modifications of the capsid protein amino acid sequence upstream or downstream of the insertion site (claim 16). Pechan teaches an embodiment wherein the polypeptide sequence is the sequence set forth in SEQ ID NO: 11, which is GGGRGDLGLSGGG (para 5, 7, 9, 53). The underlined portion of the sequence set forth in SEQ ID NO: 11 of Pechan (“Db” in the alignment below) is 100% identical to the sequence set forth in SEQ ID NO: 1 of the instant application (“Qy” in the alignment below):
Query Match 100.0%; Score 35; DB 1; Length 13;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RGDLGLS 7
|||||||
Db 4 RGDLGLS 10
The sequence set forth in SEQ ID NO: 11 of Pechan comprises residues of GGG at the N-terminal and C-terminal ends of the sequence set forth in SEQ ID NO: 1 of the instant application (claims 16-18). The sequence set forth in SEQ ID NO: 11 of Pechan consists of 13 amino acids (claim 19).
Pechan teaches that the polypeptide sequence is inserted between residues 588 and 589 of the wildtype AAV9 VP1 capsid, which corresponds to variable region VIII, or to corresponding residues in non-AAV9 capsids, including AAV6, AAV8, and AAVrh.74 (para 5-6) (claims 20-22).
Pechan teaches that the modified AAV capsid protein taught therein has an increased tropism for cardiac and/or skeletal muscle (para 28), and decreased tropism for liver (para 29) (claim 26).
Pechan teaches a polynucleotide encoding the modified AAV capsid polypeptide taught therein (para 22, 24) (claim 27).
Pechan teaches a vector (reads on plasmid) comprising the polynucleotide taught therein (para 24) (claim 29). Pechan teaches that the AAV vector may carry any gene of interest for treating a disease or condition through gene therapy (para 65, 70) (claims 30-31). Pechan teaches administering to a subject a therapeutically effective amount of the recombinant AAV of the invention (para 27), as well as a cell stably transduced by an AAV vector of the invention (para 92, 95) (claim 32).
Claim(s) 16-23 and 25-32 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Richard (WO 2019/193119 A1; cited in IDS filed 01/09/2025).
Richard teaches a hybrid AAV9.rh74 capsid, which has a reduced liver tropism compared to the parent AAV9 and AAVrh74 capsid proteins (Abstract). Richard teaches that the hybrid AAV9.rh74 capsid also has high titer AAV vector production and high gene transduction efficiencies in skeletal and cardiac muscle tissues, and are useful in gene therapy of neuromuscular disorders, including genetic diseases, autoimmune diseases, neurodegenerative diseases and cancer (p 3, para 2-4). Richard teaches that the hybrid AAV9.rh74 vector can be modified with an insertion of a muscle-targeting peptide (claim 6; p 7, para 4 – p 8, para 1), including the P1 peptide, which has the sequence RGDLGLS (p 37, Example 3), which is 100% identical to the sequence set forth in SEQ ID NO: 1 of the instant application (claim 16):
Query Match 100.0%;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RGDLGLS 7
|||||||
Db 1 RGDLGLS 7
Richard teaches that the insertion of the peptide may not cause the deletion of the residues from the insertion site (reads on without modification of the capsid protein amino acid sequence upstream and downstream of the insertion site of claim 16) (p 8, para 1), and that the peptide may include fixed sequences of up to five amino acids at its N- and C-terminal ends, including GQSG at the N-terminal end and AQAA at the C-terminal end (p 8, para 1) (claims 16-19). Richards teaches that the insertion site is advantageously between positions 587 to 592 according to the numbering in SEQ ID NO: 1, which is the amino acid sequence of AAV9 (p 8, para 1). Residues 587 to 592 of the AAV9 capsid, corresponds to variable region VIII (claims 20-21, 23). The capsid taught in Richard is a hybrid AAV9.rh74 capsid (Abstract) (claims 22-23).
Regarding claim 25: Richard teaches that the hybrid AAV9.rh74 capsid comprising peptide P1 has the amino acid sequence set forth in SEQ ID NO: 9. The sequence set forth in SEQ ID NO: 6 of the instant application (“Qy” in the alignment below) is 98.4% identical to the sequence set forth in SEQ ID NO: 9 of Richard:
Query Match 98.4%; Score 3979.5; Length 746;
Best Local Similarity 98.9%;
Matches 741; Conservative 2; Mismatches 3; Indels 3; Gaps 2;
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 PFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNWL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNWL 480
Qy 481 PGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSSG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 PGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSSG 540
Qy 541 VLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAARGDLGLSS 600
|||||||||||||||||||||||||||||||||||||||||||||| | : |||||||:
Db 541 VLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQGQ--SGRGDLGLSA 598
Qy 601 GAAPIVGAVNSQGALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQI 660
|| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 599 QAA-IVGAVNSQGALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQI 657
Qy 661 LIKNTPVPADPPTAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYK 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 658 LIKNTPVPADPPTAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYK 717
Qy 721 SNNVEFAVNTEGVYSEPRPIGTRYLTRNL 749
|||||||||||||||||||||||||||||
Db 718 SNNVEFAVNTEGVYSEPRPIGTRYLTRNL 746
Richard teaches that the AAV9.rh74 capsid protein has an increased tropism for cardiac and/or skeletal muscle, and decreased tropism for liver (Abstract; p 3, para 2-4) (claim 26). Richard teaches a polynucleotide encoding the modified AAV capsid polypeptide taught therein (p 9, para 2-5) (claim 27).
Regarding claim 28: SEQ ID NO: 7 of the instant application (“Qy” in the alignment below) has 99.0% similarity to the sequence set forth in SEQ ID NO: 10 of Richard (“Db” in the alignment below), which is the coding sequence of the hybrid AVV9.rh74 modified with peptide P1 (p 37, Example 3):
Query Match 97.4%; Score 2191.2; Length 2241;
Best Local Similarity 99.0%;
Matches 2228; Conservative 0; Mismatches 13; Indels 9; Gaps 2;
Qy 1 ATGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTTAGTGAAGGAATTCGC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTTAGTGAAGGAATTCGC 60
Qy 61 GAGTGGTGGGCTTTGAAACCTGGAGCCCCTCAACCCAAGGCAAATCAACAACATCAAGAC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GAGTGGTGGGCTTTGAAACCTGGAGCCCCTCAACCCAAGGCAAATCAACAACATCAAGAC 120
Qy 121 AACGCTCGAGGTCTTGTGCTTCCGGGTTACAAATACCTTGGACCCGGCAACGGACTCGAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AACGCTCGAGGTCTTGTGCTTCCGGGTTACAAATACCTTGGACCCGGCAACGGACTCGAC 180
Qy 181 AAGGGGGAGCCGGTCAACGCAGCAGACGCGGCGGCCCTCGAGCACGACAAGGCCTACGAC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 AAGGGGGAGCCGGTCAACGCAGCAGACGCGGCGGCCCTCGAGCACGACAAGGCCTACGAC 240
Qy 241 CAGCAGCTCAAGGCCGGAGACAACCCGTACCTCAAGTACAACCACGCCGACGCCGAGTTC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CAGCAGCTCAAGGCCGGAGACAACCCGTACCTCAAGTACAACCACGCCGACGCCGAGTTC 300
Qy 301 CAGGAGCGGCTCAAAGAAGATACGTCTTTTGGGGGCAACCTCGGGCGAGCAGTCTTCCAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CAGGAGCGGCTCAAAGAAGATACGTCTTTTGGGGGCAACCTCGGGCGAGCAGTCTTCCAG 360
Qy 361 GCCAAAAAGAGGCTTCTTGAACCTCTTGGTCTGGTTGAGGAAGCGGCTAAGACGGCTCCT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GCCAAAAAGAGGCTTCTTGAACCTCTTGGTCTGGTTGAGGAAGCGGCTAAGACGGCTCCT 420
Qy 421 GGAAAGAAGAGGCCTGTAGAGCAGTCTCCTCAGGAACCGGACTCCTCCGCGGGTATTGGC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GGAAAGAAGAGGCCTGTAGAGCAGTCTCCTCAGGAACCGGACTCCTCCGCGGGTATTGGC 480
Qy 481 AAATCGGGTGCACAGCCCGCTAAAAAGAGACTCAATTTCGGTCAGACTGGCGACACAGAG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 AAATCGGGTGCACAGCCCGCTAAAAAGAGACTCAATTTCGGTCAGACTGGCGACACAGAG 540
Qy 541 TCAGTCCCAGACCCTCAACCAATCGGAGAACCTCCCGCAGCCCCCTCAGGTGTGGGATCT 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 TCAGTCCCAGACCCTCAACCAATCGGAGAACCTCCCGCAGCCCCCTCAGGTGTGGGATCT 600
Qy 601 CTTACAATGGCTTCAGGTGGTGGCGCACCAGTGGCAGACAATAACGAAGGTGCCGATGGA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 CTTACAATGGCTTCAGGTGGTGGCGCACCAGTGGCAGACAATAACGAAGGTGCCGATGGA 660
Qy 661 GTGGGTAGTTCCTCGGGAAATTGGCATTGCGATTCCCAATGGCTGGGGGACAGAGTCATC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GTGGGTAGTTCCTCGGGAAATTGGCATTGCGATTCCCAATGGCTGGGGGACAGAGTCATC 720
Qy 721 ACCACCAGCACCCGAACCTGGGCCCTGCCCACCTACAACAATCACCTCTACAAGCAAATC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 ACCACCAGCACCCGAACCTGGGCCCTGCCCACCTACAACAATCACCTCTACAAGCAAATC 780
Qy 781 TCCAACAGCACATCTGGAGGATCTTCAAATGACAACGCCTACTTCGGCTACAGCACCCCC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 TCCAACAGCACATCTGGAGGATCTTCAAATGACAACGCCTACTTCGGCTACAGCACCCCC 840
Qy 841 TGGGGGTATTTTGACTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 TGGGGGTATTTTGACTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGA 900
Qy 901 CTCATCAACAACAACTGGGGATTCCGGCCTAAGCGACTCAACTTCAAGCTCTTCAACATT 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 CTCATCAACAACAACTGGGGATTCCGGCCTAAGCGACTCAACTTCAAGCTCTTCAACATT 960
Qy 961 CAGGTCAAAGAGGTTACGGACAACAATGGAGTCAAGACCATCGCCAATAACCTTACCAGC 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 CAGGTCAAAGAGGTTACGGACAACAATGGAGTCAAGACCATCGCCAATAACCTTACCAGC 1020
Qy 1021 ACGGTCCAGGTCTTCACGGACTCAGACTATCAGCTCCCGTACGTGCTCGGGTCGGCTCAC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 ACGGTCCAGGTCTTCACGGACTCAGACTATCAGCTCCCGTACGTGCTCGGGTCGGCTCAC 1080
Qy 1081 GAGGGCTGCCTCCCGCCGTTCCCAGCGGACGTTTTCATGATTCCTCAGTACGGGTATCTG 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 GAGGGCTGCCTCCCGCCGTTCCCAGCGGACGTTTTCATGATTCCTCAGTACGGGTATCTG 1140
Qy 1141 ACGCTTAATGATGGAAGCCAGGCCGTGGGTCGTTCGTCCTTTTACTGCCTGGAATATTTC 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 ACGCTTAATGATGGAAGCCAGGCCGTGGGTCGTTCGTCCTTTTACTGCCTGGAATATTTC 1200
Qy 1201 CCGTCGCAAATGCTAAGAACGGGTAACAACTTCCAGTTCAGCTACGAGTTTGAGAACGTA 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 CCGTCGCAAATGCTAAGAACGGGTAACAACTTCCAGTTCAGCTACGAGTTTGAGAACGTA 1260
Qy 1261 CCTTTCCATAGCAGCTACGCTCACAGCCAAAGCCTGGACCGACTAATGAATCCACTCATC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 CCTTTCCATAGCAGCTACGCTCACAGCCAAAGCCTGGACCGACTAATGAATCCACTCATC 1320
Qy 1321 GACCAATACTTGTACTATCTCTCACGGACTCAAAGCACGGGCGGTACTGCAGGAACTCAG 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 GACCAATACTTGTACTATCTCTCACGGACTCAAAGCACGGGCGGTACTGCAGGAACTCAG 1380
Qy 1381 CAGTTGCTATTTTCTCAGGCCGGGCCTAACAACATGTCGGCTCAGGCCAAGAACTGGCTA 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 CAGTTGCTATTTTCTCAGGCCGGGCCTAACAACATGTCGGCTCAGGCCAAGAACTGGCTA 1440
Qy 1441 CCCGGTCCCTGCTACCGGCAGCAACGCGTCTCCACGACACTGTCGCAGAACAACAACAGC 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 CCCGGTCCCTGCTACCGGCAGCAACGCGTCTCCACGACACTGTCGCAGAACAACAACAGC 1500
Qy 1501 AACTTTGCCTGGACGGGTGCCACCAAGTATCATCTGAATGGCAGAGACTCTCTGGTGAAT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 AACTTTGCCTGGACGGGTGCCACCAAGTATCATCTGAATGGCAGAGACTCTCTGGTGAAT 1560
Qy 1561 CCTGGCGTTGCCATGGCTACCCACAAGGACGACGAAGAGCGATTTTTTCCATCCAGCGGA 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 CCTGGCGTTGCCATGGCTACCCACAAGGACGACGAAGAGCGATTTTTTCCATCCAGCGGA 1620
Qy 1621 GTCTTAATGTTTGGGAAACAGGGAGCTGGAAAAGACAACGTGGACTATAGCAGCGTGATG 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 GTCTTAATGTTTGGGAAACAGGGAGCTGGAAAAGACAACGTGGACTATAGCAGCGTGATG 1680
Qy 1681 CTAACCAGCGAGGAAGAAATAAAGACCACCAACCCAGTGGCCACAGAACAGTACGGCGTG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 CTAACCAGCGAGGAAGAAATAAAGACCACCAACCCAGTGGCCACAGAACAGTACGGCGTG 1740
Qy 1741 GTGGCCGATAACCTGCAACAGCAAAACGCGGCCGCCCGCGGCGATCTGGGCCTGAGCTCC 1800
|||||||||||||||||| || | | |||||||||||||||||||||| ||
Db 1741 GTGGCCGATAACCTGCAAGGCCA------GAGTGGCCGCGGCGATCTGGGCCTGAGCGCC 1794
Qy 1801 GGAGCCGCTCCTATTGTAGGGGCCGTCAATAGTCAAGGAGCCTTACCTGGCATGGTGTGG 1860
|| | | ||||||||||||||||||||||||||||||||||||||||||||||||
Db 1795 CAGGCGG---CCATTGTAGGGGCCGTCAATAGTCAAGGAGCCTTACCTGGCATGGTGTGG 1851
Qy 1861 CAGAACAGAGATGTGTACCTGCAAGGACCCATTTGGGCCAAAATTCCTCACACGGACGGC 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1852 CAGAACAGAGATGTGTACCTGCAAGGACCCATTTGGGCCAAAATTCCTCACACGGACGGC 1911
Qy 1921 AACTTTCACCCTTCTCCGCTGATGGGAGGGTTTGGAATGAAGCACCCGCCTCCTCAGATC 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1912 AACTTTCACCCTTCTCCGCTGATGGGAGGGTTTGGAATGAAGCACCCGCCTCCTCAGATC 1971
Qy 1981 CTCATCAAAAACACACCTGTACCTGCGGATCCTCCAACGGCCTTCAACAAGGACAAGCTG 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1972 CTCATCAAAAACACACCTGTACCTGCGGATCCTCCAACGGCCTTCAACAAGGACAAGCTG 2031
Qy 2041 AACTCTTTCATCACCCAGTATTCTACTGGCCAAGTCAGCGTGGAGATCGAGTGGGAGCTG 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2032 AACTCTTTCATCACCCAGTATTCTACTGGCCAAGTCAGCGTGGAGATCGAGTGGGAGCTG 2091
Qy 2101 CAGAAGGAAAACAGCAAGCGCTGGAACCCGGAGATCCAGTACACTTCCAACTATTACAAG 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2092 CAGAAGGAAAACAGCAAGCGCTGGAACCCGGAGATCCAGTACACTTCCAACTATTACAAG 2151
Qy 2161 TCTAATAATGTTGAATTTGCTGTTAATACTGAAGGTGTATATAGTGAACCCCGCCCCATT 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2152 TCTAATAATGTTGAATTTGCTGTTAATACTGAAGGTGTATATAGTGAACCCCGCCCCATT 2211
Qy 2221 GGCACCAGATACCTGACTCGTAATCTGTAA 2250
||||||||||||||||||||||||||||||
Db 2212 GGCACCAGATACCTGACTCGTAATCTGTAA 2241
Richard teaches a vector (reads on plasmid) comprising the polynucleotide taught therein (p 37, Example 3) (claim 29). Richard teaches that the AAV vector may carry a gene of interest, which may be a therapeutic gene (claims 13-14; p 1, para 1; p 11, para 4 – p 12, para 4) (claims 30-31). Richard teaches a pharmaceutical composition comprising a therapeutically acceptable amount of AAV vector particle taught therein (p 14, para 1) (claim 32).
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.
Claim(s) 16 and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Pechan (US 2024/0261437 A1), in view of Richard (WO 2019/193119 A1; cited in IDS filed 01/09/2025).
The teachings of Pechan are set forth above. Pechan anticipates claim 16.
Regarding claim 23: Pechan teaches the modified AAV capsid protein of claim 16. Pechan further teaches that the AAV serotype may be AAV9 or AAVrh.74 (para 5-6), and that the muscle-targeting peptide sequence is inserted between residues 588 and 589 of the wildtype AAV9 VP1 capsid, or to the corresponding residues in the AAVrh.74 capsid (para 5-6).
Pechan does not teach the modified AAV capsid protein of claim 16, which is from AAV9.rh74.
Richard teaches a hybrid AAV9.rh74 capsid, which has a reduced liver tropism compared to the parent AAV9 and AAVrh74 capsid proteins (Abstract). Richard teaches that the hybrid AAV9.rh74 capsid also has high titer AAV vector production and high gene transduction efficiencies in skeletal and cardiac muscle tissues, and are useful in gene therapy of neuromuscular disorders, including genetic diseases, autoimmune diseases, neurodegenerative diseases and cancer (p 3, para 2-4). Richard teaches that the hybrid AAV9.rh74 vector can be modified with an insertion of a muscle-targeting peptide (claim 6; p 7, para 4 – p 8, para 1), including the P1 peptide, which has the sequence RGDLGLS (p 37, Example 3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Pechan by using the hybrid AAV9.rh74 taught in Richard. One of ordinary skill in the art would have been motivated to make this modification because Richard teaches that the hybrid AAV9.rh74 capsid has high titer AAV vector production and high gene transduction efficiencies in skeletal and cardiac muscle tissues compared to the parent AAV9 and AAVrh74 capsid proteins. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Richard teaches that a muscle-targeting peptide can be inserted into the AAV9.rh74 capsid.
Regarding claim 24: Following the discussion of claim 16 above, Pechan teaches a sequence identified as SEQ ID NO: 11. Residues 3-11 of the sequence set forth in SEQ ID NO: 11 of Pechan (“Db” in the alignment below) is 100% identical to the sequence set forth in SEQ ID NO: 25 of the instant application (“Qy” in the alignment below):
Query Match 100.0%; Score 47; DB 1; Length 13;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GRGDLGLSG 9
|||||||||
Db 3 GRGDLGLSG 11
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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/RISA TAKENAKA/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632