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 .
Applicant’s amendment and response filed on 11/25/2025 has been received and entered into the case.
Claims 3-6, 10-11, 18, 21 have been canceled, claim 26 is newly added, claims 20 and 22-25 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-2, 7-9, 12-17, 19 and 26 have been considered on the merits. All arguments have been considered.
It is noted that applicant has elected SEQ ID NO:21 (amino acid sequence) and SEQ ID NO:20 (nucleic acid sequence) in the reply filed on 8/28/2025 as indicated in the OA mailed on 9/22/2025. The elected species are directed to a modified human arrestin-1 protein and the corresponding nucleic acid sequence.
Response to Amendment
The claim rejection under 35 USC 101 has been withdrawn due to the instant amendment.
The claim rejections under 35 USC 102 and 103 based on Chrysochloris asiatica S-antigen; retina and pineal gland (arrestin) (SAG), mRNA (2014, NCBI GenBank) have been withdrawn due to the instant amendment.
The claim rejection under 35 USC 112(a) and (b) have been withdrawn due to the instant amendment but new rejections are necessitated by the instant amendment (see below).
Claim Rejections - 35 USC § 112
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 1-2, 7-9, 12-17, and 19 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.
Claims 1 and 7: A modified arrestin-1 protein
Claim 1 discloses a modified arrestin-1 protein comprising a glycine or alanine substitution of the glutamate residue at a position corresponding to position 365 of SEQ ID NO:18 and a glycine or alanine substitution of the aspartate residue at a position corresponding to position 366 of SEQ ID NO:18. The modified arrestin-1 protein binds enolase-1 at least 80% of the binding of an arrestin-1 protein not having the substitutions, and has reduced inhibitory effect on enolase-1 catalytic activity relative to an arrestin-1 protein with the substitutions.
While the claimed arrestin-1 protein is disclosed to have the substitution at the residue based on SEQ ID NO:18 (human arrestin-1), however, the scope is not limited to the two substitution at the positions 355 and 365 of SEQ ID NO:18. The scope of the modified arrestin-1 protein as claimed would include not only the claimed substitutions at the residue 355 and 365 of SEQ ID NO:18 but also any other modification (mutations in any amino acid position; addition or deletion mutation; any other modification, etc.) to the SEQ ID NO:18, if the modified protein possesses the claimed functional properties. Furthermore, the scope would also encompass any ortholog of SEQ ID NO:18, which is a human arrestin-1 protein if the properties as claimed are met.
Thus, the scope of the claimed protein is extensive with regard to the sequence and the minimal requirement would be the functional aspect of the protein.
The properties required by the instant claim are maintained binding of the modified arrestin-1 protein to enolase-1 and reduced inhibitory effect on enolase-1 catalytic activity. The binding of arrestin-1 to enolase-1 is known in the art. However, except the two residues disclosed in the instant specification, i.e. E365/D366 of SEQ ID NO:18; or E361/D362 of SEQ ID NO:30, there is no additional information with regard to any modification that maintains the claimed properties to meet the claimed genus. Considering the total amino acid residue being over 400, there would be numerous possible mutations and yet the specification does not provide sufficient description what residues can be modified without affecting the functions of the arrestin-1 protein. There is no information whether what other modification or mutation in addition to the claimed substitutions would affect the tertiary structure of the protein to maintain or lose their properties. Thus, it is concluded that the instant specification fails to provide sufficient written description to support that the inventors had possession on the entire scope of the genus other than the species having two amino acid residues of glutamate and aspartate substituted to glycine and/or alanine. There is no indication what can be modified or mutated without affecting the arrestin-1’s natural functionality as claimed.
Claim 7 discloses the modified arrestin-1 protein comprising E365G/A and D366G/A substitution of SEQ ID NO:18. The claim is interpreted to limit that the arrestin-1 protein contains the amino acid sequence of SEQ ID NO: 18 except the mutations indicated. However, the claim does not exclude any other modification than the two substitution, and thus, the scope of claim 7 is as extensive as claim 1 because it does not limit any other additional mutations or modification.
Claim 8: the arrestin-1 variant
Claim 8 discloses that the arrestin-1 variant has the amino acid sequence of SEQ ID NO:21 (elected species) and an ortholog thereof or amino acid sequence having at least 70% identity to SEQ ID NO:21. Even though this claim limits the amino acid sequence of the claimed arrestin-1 variant at least 70% identical to SEQ ID NO:21, however, the instant specification fails to provide to support that the inventors had possession of the entire scope of the genus as there is no written description such that one skilled in the art would modify the sequence within the claimed 70% identity and yet to maintain the functionality of the variants within the genus.
Thus, while the specification showed the examples of the claimed modified arrestin-1 protein (i.e. SEQ ID NO:6, 9-12 or 21-24), however, there is no sufficient written description for the genus of those having at least 70% identity to SEQ ID NO: 6, 9-12 or 21-24.
Regarding claim 14 directed to the nucleic acid sequence of SEQ ID NO:17 or 18 in claim 13 being a nucleic acid having at least 70% identity to SEQ ID NO: 5, 7, 8, 19 or 20 (SEQ ID NO:20 is elected species), there is no written description with regard to the genus having at least 70% identity to these sequences, and thus, the inventor did not have possession for the entire scope of the claimed invention.
M.P.E.P. §2163 recites, “The written description requirement for a claimed genus may be satisfied 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…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.”
Therefore, it is the Examiner’s position that the instant specification fails to provide sufficient written description to support that the inventors had possession on the entire scope of the claimed invention.
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 7-9 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 7 is dependent on claim 6 which has been canceled. As the claim is dependent on the canceled claim, it is indefinite what claim 7 is referring to. Clarification is required. Claim 7 is interpreted as being dependent on claim 1.
Claim 8 discloses “the arrestin-1 variant”. There is no antecedent basis for the term “variant” as claim 1 has been amended and no longer discloses the term “variant”.
Claim 8 discloses the phrase “an ortholog thereof” in line 2. It is not clear if the scope of “ortholog” limits only those having E (glutamate) and D (aspartate) at the position of residues 365 and 366 and if so, the orthologs having different amino acid residue at this position would be excluded. According to the instant specification, the E and D residues are in different position in different ortholog (para. 55). Clarification is required. For search purpose, the claim is interpreted as any arrestin-1 protein having E and/or D residue being A or G in the corresponding position based on SEQ ID NO:18 or SEQ ID NO:21.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 2 discloses that the modified arrestin-1 protein is a variant of an arrestin-1 protein comprising the amino acid sequence of SEQ ID NO:4, 18 or 30. Claim 1 discloses that the modified arrestin-1 is based on SEQ ID NO:18 which is understood as a human arrestin-1. However, claim 2 discloses SEQ ID NO:4 and 30, which are mouse (Mus musculus) and bovine (Bos taurus), respectively. Thus, the limitation of claim 2 does not further limit the subject matter of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 7-9, 12, 15-17 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Ostermaier et al. (2014, PNAS; of record) in view of Lefevre et al. (1997, Nucleic Acids Research; of record)
Ostermaier et al. teach scanning mutagenesis of bovine arrestin-1 and a single amino acid residue of arrestin-1 was mutated to alanine (i.e. aka alanine scanning) (see p.1825, Results and Discussion; Table S1). Ostermaier et al. teach that the single amino acid mutation includes E361A or D362A, and these two separate mutations would meet the alanine substitution of glutamate or aspartate corresponding to positions 365 or 366 of SEQ ID NO:18, and the E361A. The positions 361 and 362 of bovine arrestin-1 (see Genbank data) is matching to positions 365 and 366 of SEQ ID NO:18 (see alignment below).
RESULT 1
AASEQ2_09172025_084121
Query Match 80.4%; Score 1667; DB 1; Length 370;
Best Local Similarity 87.2%;
Matches 321; Conservative 25; Mismatches 20; Indels 2; Gaps 1;
Qy 6 KTSKSEPNHVIFKKISRDKSVTIYLGNRDYIDHVSQVQPVDGVVLVDPDLVKGKKVYVTL 65
| :| |||||||||||||||||||| ||||||| :|:||||||||||:|||||:|||:|
Db 2 KANKPAPNHVIFKKISRDKSVTIYLGKRDYIDHVERVEPVDGVVLVDPELVKGKRVYVSL 61
Qy 66 TCAFRYGQEDIDVIGLTFRRDLYFSRVQVYPPVGAASTPTKLQESLLKKLGSNTYPFLLT 125
|||||||||||||:||:||||||||:|||:|||||: |:|||||:||||:||||||||
Db 62 TCAFRYGQEDIDVMGLSFRRDLYFSQVQVFPPVGASGATTRLQESLIKKLGANTYPFLLT 121
Qy 126 FPDYLPCSVMLQPAPQDSGKSCGVDFEVKAFATDSTDAEEDKIPKKSSVRLLIRKVQHAP 185
||||||||||||||||| |||||||||:||||| ||| ||||||||||||||||||||||
Db 122 FPDYLPCSVMLQPAPQDVGKSCGVDFEIKAFATHSTDVEEDKIPKKSSVRLLIRKVQHAP 181
Qy 186 LEMGPQPRAEAAWQFFMSDKPLHLAVSLNKEIYFHGEPIPVTVTVTNNTEKTVKKIKAFV 245
:|||||||||:|||||||||| |||||:||||:||||||||| |||:||||||||| |
Db 182 RDMGPQPRAEASWQFFMSDKPLRLAVSLSKEIYYHGEPIPVTVAVTNSTEKTVKKIKVLV 241
Qy 246 EQVANVVLYSSDYYVKPVAMEEAQEKVPPNSTLTKTLTLLPLLANNRERRGIALDGKIKH 305
||| ||||||||||:| || |||||||||||:|||||||:||||||||||||||||||||
Db 242 EQVTNVVLYSSDYYIKTVAAEEAQEKVPPNSSLTKTLTLVPLLANNRERRGIALDGKIKH 301
Qy 306 EDTNLASSTIIKEGIDRTVLGILVSYQIKVKLTVSGFLGELTSSEVATEVPFRLMHPQPE 365
||||||||||||||||:||:|||||||||||||||| |||||||||||||||||||||||
Db 302 EDTNLASSTIIKEGIDKTVMGILVSYQIKVKLTVSGLLGELTSSEVATEVPFRLMHPQPE 361
Qy 366 DP--AKES 371
|| ||||
Db 362 DPDTAKES 369
Ostermaier et al. do not teach that both of E361A and D362A in the bovine arrestin-1.
However, it is known in the art that multiple alanine mutations or alanine stretch scanning mutagenesis can be utilized for functional mapping of a protein according to Lefevre et al. Lefevre et al. teach substitution of a stretch of two to six residues by alanines (Abstract), and this method is efficient to probe protein structure and function (see entire document).
It would have been obvious to a person skilled in the art to use two or more alanine substitution in arrestin-1 taught by Ostermaier et al. A person of ordinary skilled in the art would have been motivated to do so because Lefevre et al. teach that alanine stretch mutagenesis method can be used as a probe to rapidly scan a whole protein sequence in search of secondary structures or to characterize the catalytic or functional role of a stretch of residues and this method is relatively simple, and highly reliable, as a simple screening can be performed at each step (p.448, 2nd col.).
Thus, by using the alanine stretch mutagenesis taught by Lefevre et al. over the single alanine mutagenesis of Ostermaier et al., one skilled in the art would be able to study function of arrestin-1 of Ostermaier et al. The stretch alanine mutagenesis in the position 361 and 362 would meet the limitation of claims 1 and 7 directed to alanine substitutions corresponding to positions 365 and 366 of SEQ ID NO:18.
Regarding claim 2, the SEQ ID NO: 30 as claimed is directed to bovine arrestin-1. As Ostermaier et al. teach bovine arrestin-1 and mutagenesis on its amino acid residue, the combined teachings of Ostermaier et al. in view of Lefevre et al. would meet the subject matter of claim 2.
Regarding claim 8, the bovine arrestin-1 with a single mutation (i.e. E361A or D362A) would meet the limitation directed to an amino acid sequence having at least 70% identity to SEQ ID NO:21 as the bovine arrestin-1 is about 80% identical to SEQ ID NO:21 (see alignment below). Thus, E361A and D362A double mutation would result in close to 80% to SEQ ID NO:21.
Query Match 79.7%; Score 1653; DB 1; Length 370;
Best Local Similarity 86.7%;
Matches 319; Conservative 25; Mismatches 22; Indels 2; Gaps 1;
Qy 6 KTSKSEPNHVIFKKISRDKSVTIYLGNRDYIDHVSQVQPVDGVVLVDPDLVKGKKVYVTL 65
| :| |||||||||||||||||||| ||||||| :|:||||||||||:|||||:|||:|
Db 2 KANKPAPNHVIFKKISRDKSVTIYLGKRDYIDHVERVEPVDGVVLVDPELVKGKRVYVSL 61
Qy 66 TCAFRYGQEDIDVIGLTFRRDLYFSRVQVYPPVGAASTPTKLQESLLKKLGSNTYPFLLT 125
|||||||||||||:||:||||||||:|||:|||||: |:|||||:||||:||||||||
Db 62 TCAFRYGQEDIDVMGLSFRRDLYFSQVQVFPPVGASGATTRLQESLIKKLGANTYPFLLT 121
Qy 126 FPDYLPCSVMLQPAPQDSGKSCGVDFEVKAFATDSTDAEEDKIPKKSSVRLLIRKVQHAP 185
||||||||||||||||| |||||||||:||||| ||| ||||||||||||||||||||||
Db 122 FPDYLPCSVMLQPAPQDVGKSCGVDFEIKAFATHSTDVEEDKIPKKSSVRLLIRKVQHAP 181
Qy 186 LEMGPQPRAEAAWQFFMSDKPLHLAVSLNKEIYFHGEPIPVTVTVTNNTEKTVKKIKAFV 245
:|||||||||:|||||||||| |||||:||||:||||||||| |||:||||||||| |
Db 182 RDMGPQPRAEASWQFFMSDKPLRLAVSLSKEIYYHGEPIPVTVAVTNSTEKTVKKIKVLV 241
Qy 246 EQVANVVLYSSDYYVKPVAMEEAQEKVPPNSTLTKTLTLLPLLANNRERRGIALDGKIKH 305
||| ||||||||||:| || |||||||||||:|||||||:||||||||||||||||||||
Db 242 EQVTNVVLYSSDYYIKTVAAEEAQEKVPPNSSLTKTLTLVPLLANNRERRGIALDGKIKH 301
Qy 306 EDTNLASSTIIKEGIDRTVLGILVSYQIKVKLTVSGFLGELTSSEVATEVPFRLMHPQPG 365
||||||||||||||||:||:|||||||||||||||| ||||||||||||||||||||||
Db 302 EDTNLASSTIIKEGIDKTVMGILVSYQIKVKLTVSGLLGELTSSEVATEVPFRLMHPQPE 361
Qy 366 GP--AKES 371
| ||||
Db 362 DPDTAKES 369
Regarding claim 9, the bovine arrestin-1 mutants of Ostermaier et al. meet the mammalian ortholog.
Regarding claim 12, as Ostermaier et al. in view of Lefevre et al. teach E361A and D362A double mutation of bovine arrestin-1, it is inherent that the mutants were produced by the nucleic acid encoding thereof.
Regarding claim 15-17, Ostermaier et al. teach the use of EgWoMiPi vector for expression of arrestin-1 mutants in bacterial and mammalian cells (p.6, Materials and Methods). The vector of Ostermaier et al. is considered as a plasmid vector.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 13-14 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ostermaier et al. as applied to claims 1-2, 7-9, 12, 15-17 and 26 above, and further in view of Michalakis et al. (WO2018/172961; IDS ref.).
Regarding claim 13-14 directed to the nucleic acid encoding the arrestin-1 variant of claim 1, the nucleic acid sequence of the bovine arrestin-1 mutants of Ostermaier et al. has more than 70% identity to SEQ ID NO:20 (elected species). The nucleic acid sequence encoding bovine arrestin-1 contain the GAGGAC sequence encoding ED and it would have been obvious to a person skilled in the art to modify the GAGGAC sequence to known codon for alanine for the mutants taught by Ostermaier et al. The codon sequence of GAG (glutamate) or GAC (aspartate) would be mutated to GCT, GCC, GCA or GCG, as these 4 codons encode alanine. Thus, one skilled in the art would use one of these 4 codon for alanine mutation for E361A or D362A of Ostermaier et al. with a reasonable expectation of success. For those 4 codons, i.e. GCC, GCA, GCT or GCC, the sequence would meet GCNGCN of claim 13 as N is A, G, C or T.
Title: US-17-906-098-20
Perfect score: 1213
Sequence: 1 atggcagccagcgggaagac..........acaagaatgacgttgatgag 1215
RESULT 1
NASEQ2_09172025_085924
Query Match 70.0%; Score 848.6; DB 1; Length 1693;
Best Local Similarity 85.4%;
Matches 944; Conservative 0; Mismatches 161; Indels 0; Gaps 0;
Qy 1 ATGGCAGCCAGCGGGAAGACCAGCAAGTCCGAACCGAACCATGTTATCTTCAAGAAGATC 60
| ||||||||| |||| ||| ||| ||| ||| ||||| ||||||||||||||||||
Db 163 ACGGCAGCCAGTATGAAGGCCAATAAGCCCGCACCAAACCACGTTATCTTCAAGAAGATC 222
Qy 61 TCCCGGGACAAATCGGTGACCATCTACCTGGGGAACAGAGACTACATAGACCATGTCAGC 120
||||| || |||||||||||||||||||||||||| ||||| ||||||||||| ||
Db 223 TCCCGTGATAAATCGGTGACCATCTACCTGGGGAAGAGAGATTACATAGACCACGTTGAA 282
Qy 121 CAAGTCCAGCCTGTGGATGGTGTCGTGTTGGTTGATCCTGATCTTGTGAAGGGAAAGAAA 180
| ||| ||||||||||||| |||||| |||| |||||||| || |||||||| |||| |
Db 283 CGAGTAGAGCCTGTGGATGGCGTCGTGCTGGTGGATCCTGAGCTCGTGAAGGGCAAGAGA 342
Qy 181 GTGTATGTCACTCTGACCTGCGCCTTCCGCTATGGCCAAGAGGACATTGACGTGATCGGC 240
||||| || ||||||| || ||||||||||| ||||| || ||||| |||||||| |||
Db 343 GTGTACGTGTCTCTGACGTGTGCCTTCCGCTACGGCCAGGAAGACATCGACGTGATGGGC 402
Qy 241 TTGACCTTCCGCAGGGACCTGTACTTCTCCCGGGTCCAGGTGTATCCTCCTGTGGGGGCC 300
| | ||||||||||||||| |||||||||| ||||||||||| ||||| |||||||||
Db 403 CTCAGCTTCCGCAGGGACCTCTACTTCTCCCAGGTCCAGGTGTTCCCTCCCGTGGGGGCC 462
Qy 301 GCGAGCACCCCCACAAAACTGCAAGAGAGCCTGCTTAAAAAGCTGGGGAGCAACACGTAC 360
|| || || |||| | ||||| |||||||| | || ||||||||| |||||| |||
Db 463 TCGGGCGCCACCACGAGGCTGCAGGAGAGCCTCATCAAGAAGCTGGGGGCCAACACCTAC 522
Qy 361 CCCTTTCTCCTGACGTTTCCTGACTACTTGCCCTGTTCAGTGATGTTGCAGCCAGCTCCA 420
||||| || || |||||||||||||||||||||||||| |||||| |||||||||||||
Db 523 CCCTTCCTGCTCACGTTTCCTGACTACTTGCCCTGTTCGGTGATGCTGCAGCCAGCTCCG 582
Qy 421 CAAGATTCAGGGAAGTCCTGTGGGGTTGACTTTGAGGTCAAAGCATTCGCCACAGACAGC 480
|||||| || ||| ||||||||| ||||||||| |||||||||||||||| |||||
Db 583 CAAGATGTGGGCAAGAGCTGTGGGGTCGACTTTGAGATCAAAGCATTCGCCACGCACAGC 642
Qy 481 ACCGATGCCGAAGAGGACAAAATCCCCAAGAAGAGCTCCGTGCGATTACTGATCCGCAAA 540
|| |||| |||||||||||||| |||||||||||||||||||| || |||||||| ||
Db 643 ACAGATGTGGAAGAGGACAAAATTCCCAAGAAGAGCTCCGTGCGTTTGCTGATCCGGAAG 702
Qy 541 GTACAGCATGCCCCACTTGAGATGGGTCCCCAGCCCCGAGCTGAGGCGGCCTGGCAGTTC 600
|||||||| || |||| || |||||||||||||||||||| ||||| |||||||||||
Db 703 GTACAGCACGCGCCACGCGATATGGGTCCCCAGCCCCGAGCCGAGGCCTCCTGGCAGTTC 762
Qy 601 TTCATGTCTGACAAGCCCCTGCACCTTGCGGTCTCTCTCAACAAAGAGATCTATTTCCAT 660
|||||||| ||||||||||||| ||| || ||||| |||| |||||||||||||| |||
Db 763 TTCATGTCGGACAAGCCCCTGCGCCTCGCCGTCTCGCTCAGCAAAGAGATCTATTACCAC 822
Qy 661 GGGGAGCCCATCCCTGTGACCGTGACTGTCACCAATAACACAGAGAAGACCGTGAAGAAG 720
||||| ||||| |||||||||||| | || ||||| | |||||||||||| |||||||||
Db 823 GGGGAACCCATTCCTGTGACCGTGGCCGTGACCAACAGCACAGAGAAGACAGTGAAGAAG 882
Qy 721 ATTAAAGCATTCGTGGAACAGGTGGCCAATGTGGTTCTCTACTCGAGTGATTATTACGTC 780
||||||| | ||||| || ||| |||| ||||||||||||||||||||||||||| ||
Db 883 ATTAAAGTGCTAGTGGAGCAAGTGACCAACGTGGTTCTCTACTCGAGTGATTATTACATC 942
Qy 781 AAGCCCGTGGCTATGGAGGAAGCGCAAGAAAAAGTGCCACCAAACAGCACTTTGACCAAG 840
||| | |||||| |||||||| || ||||||||||| ||||||||| | ||||||||
Db 943 AAGACGGTGGCTGCCGAGGAAGCACAGGAAAAAGTGCCGCCAAACAGCTCGCTGACCAAG 1002
Qy 841 ACGCTGACGCTGCTGCCCTTGCTGGCTAACAATCGAGAAAGGAGAGGCATTGCCCTGGAT 900
|||||||||||| ||||||||||||| ||||| || || || || ||||| |||||||||
Db 1003 ACGCTGACGCTGGTGCCCTTGCTGGCCAACAACCGTGAGAGAAGGGGCATCGCCCTGGAT 1062
Qy 901 GGGAAAATCAAGCACGAGGACACAAACCTTGCCTCCAGCACCATCATTAAGGAGGGCATA 960
||||||||||||||||||||||| ||||| ||||||||||||||||| |||||||| |||
Db 1063 GGGAAAATCAAGCACGAGGACACGAACCTGGCCTCCAGCACCATCATAAAGGAGGGAATA 1122
Qy 961 GACCGGACCGTCCTGGGAATCCTGGTGTCTTACCAGATCAAGGTGAAGCTCACAGTGTCA 1020
||| ||||||| |||| ||||||||||||||||||||||||||||||||||| ||||||
Db 1123 GACAAGACCGTCATGGGGATCCTGGTGTCTTACCAGATCAAGGTGAAGCTCACGGTGTCA 1182
Qy 1021 GGCTTTCTGGGAGAGCTCACCTCCAGTGAAGTCGCCACTGAGGTCCCATTCCGCCTCATG 1080
||| |||||||||||||||| ||||||||||| ||||||||||| || ||||||||||||
Db 1183 GGCCTTCTGGGAGAGCTCACATCCAGTGAAGTGGCCACTGAGGTGCCGTTCCGCCTCATG 1242
Qy 1081 CACCCTCAGCCTGGNGGNCCAGCTA 1105
|| || ||||| | | |||| ||
Db 1243 CATCCCCAGCCAGAGGACCCAGATA 1267
Claims 15-17 and 19 directed to the vector encoding the arrestin-1 variant of claim 1 or comprising the nucleotide of claim 12, and the vector being AAV, while Ostermaier et al. teach the use of plasmid vector as discussed supra, however, they do not teach the AAV vector.
Michalakis et al. teach the transgene including S-antigen visual arrestin (SAG) or variant thereof (p.17, lines 1-3) and an AAV vector for the expression of the transgene (p.24, lines 1-17).
It would have been obvious to a person skilled in the art to use the AAV vector for expression of bovine arrestin-1 taught by Ostermaier et al. replacing the plasmid vector (i.e. EgWoMiPi vector) with a reasonable expression of success. A person of ordinary skilled in the art would have been motivated to do so because Michalakis et al. teach the expression of SAG from any variant or source thereof, and one skilled in the art would consider the AAV vector is suitable for expressing the arrestin-1 mutants including E361A or D362A taught by Ostermaier et al.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ostermaier et al. in view of Lefevre et al. as applied to claims 1-2, 7-9, 12, 15-17 and 26 above, and further in view of Liu et al. (US 2006/0100148A1)
Regarding claim 26, the arrestin-1 variant comprising SEQ ID NO:21 (elected species) has glycine substitution at the position 365 (E365G) and 366 (E366G) of SEQ ID NO:18 (human arrestin-1). While Ostermaier et al. in view of Lefevre et al. teach bovine arrestin-1 and alanine scanning mutagenesis at the amino acid residues corresponding to position 365 and 366 of SEQ ID NO:18, i.e. E365A and D366A, however, they do not teach E365G and D366G of human arrestin-1.
It would have been obvious to a person skilled in the art to use human arrestin-1 protein to carry out alanine scanning study taught by Ostermaier et al. with a reasonable expectation of success. By doing so, one skilled in the art would arrive the SEQ ID NO:25 or SEQ ID NO:26. As discussed above, based on the teaching by Lefevre et al., double alanine substitutions would be within the purview of the artisan. As glycine scanning mutagenesis is known in the art for studying functional aspects of proteins along with Ala scanning according to Liu et al. (para. 257). Liu et al. teach amino acid scanning experiments to determine the amino acid residue required for the activity of peptide, and utilized both Gly scanning and Ala scanning. It would have been obvious to a person skilled in the art to utilize Gly scanning for the same purpose of Ala scanning taught by Ostermaier et al. in view of Lefevre et al. with a reasonable expectation of success. By doing so, one skilled in the art would arrive the E365G and D366G as claimed for SEQ ID NO:21.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-3, 6-9 and 11-18 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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