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 .
Claims Status
Claims 1-2, 4, 7-12, 14-15, 22, 30, 32, and 43-48 are pending.
Claims 1, 10-12, 30 and 32 are amended.
Claims 3, 5-6, 13, 16-21, 23-29, 31, and 33-42 are cancelled.
Election/Restrictions
Applicant’s election of Group 1 (Claims 1-2, 4, 7-12, 14-15, 30, 32, and 43-44) in the reply filed on 07/20/2026 is acknowledged. Upon further review, the Examiner has rejoined claims 30 and 32 to Group 1. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant’s election of Species Group 1: (3) AAV2 genome and ASV8 capsid proteins in the reply filed on 07/20/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 22 and 45-48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/20/2026.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/14/2023 and 01/15/2026 are acknowledged. The submission is in compliance with the provision of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 10 is 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.
With regards to claim 10, the claim recites “a first amino acid sequence selected from an amino acid sequence as set forth in SEQ ID NO.2 (heavy chain)”….”and a second amino acid sequence as set forth in SEQ ID NO. 3 (light chain)”. It is unclear if the terms in parenthesis are meant to serve as additional limitations to the claim and thus the claim is rendered indefinite. In the interest of compact prosecution, the Examiner is interpreting the terms “(heavy chain)” to refer to SEQ ID NO. 2 being identified with the heavy chain of complement factor I and the term “(light chain)” to refer to SEQ ID NO.3 being identified with the light chain of complement factor I.
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.
Claims 1-2, 4, 8, 30 and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, vol. 32, pg. 379-387, published April 1995: PMID: 7739577), hereinafter referred to as Wong, in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150), hereinafter referred to as Urabe.
With regards to claims 1-2, 4, 8, 30 and 43-44, Wong teaches that Human Factor I is a disulfide-linked heterodimer composed of a heavy (H) chain and a light (L) chain (see pg. 379, right column, 2nd paragraph). Wong teaches that Factor I is an active plasma serine proteinase which regulates the classical and alternative pathway C3 convertases of the complement system (see pg. 379, left column, 1st paragraph). Wong further teaches that a full-length human factor I cDNA was cloned into the pMT2 expression vector and the pMT2-fI construct was expressed transiently in COS-1 cells and stably in CHO-K1 cells. Wong further teaches that co-transfection of COS-1 cells with pMT2-fI and the cDNA expression plasmid for PACE (paired basic amino acid cleaving enzyme) resulted predominantly in the secretion of a proteolytically processed (mature) form of recombinant factor I (heavy chain, 47 kD; light chain,35 KD) (see Abstract, pg. 379). PACE is a subtilisin like protease (PACE/furin) as evidenced by Wasley et al. (The Journal of Biological Chemistry, Vol. 268, pg. 8458-8465, published 1993).
Wong does not teach an expression vector that comprises a nucleic acid encoding a recombinant precursor complement factor 1 protein and a nucleic acid encoding a furin protein or that the expression vector is a viral vector, AAV, or that the expression vector comprises a nucleic acid molecule encoding an internal ribosome entry site (IRES).
However, Urabe teaches the development of a novel dicistronic AAV vector containing a 230 base pairs internal ribosome entry site (IRES) element (see Abstract, pg. 157). Urabe teaches that the dicistronic AAV vector harboring HCV IRES-bsr is capable of expressing a therapeutic gene as well as a selectable marker gene. Urabe teaches that if a selectable marker gene is not necessary, the vector is able to incorporate two different kinds of therapeutic genes and that the discistronic AAV vector is useful for expressing many kinds of cDNA besides a selectable marker (see Abstract, pg. 157). Urabe also teaches that the expression vector is comprises a CMV promoter element (upstream from the first gene and second gene) (see Figure 1, pg. 158). Urabe teaches that the IRES segment is positioned between the first cistron and second cistron to be expressed (see pg. 158, Figure 1). Urabe teaches that 293 cells were transfected with the dicistronic plasmid vectors (see Section 2.3, pg. 159).
It would have been obvious to one of ordinary skill in the art of protein engineering before the effective filing date of the current instant application, to modify the teachings of Wong by using the dicistronic AAV vector taught by Urabe as an alternative option for expressing the complement factor I and PACE/furin protein together in the same vector instead of expressing the complement factor I and PACE proteins in separate expression vectors as taught by Wong. One of ordinary skill in the art would be motivated to do so by the teachings of Urabe who teach that the dicistronic AAV vector can express two genes from the same vector. One of ordinary skill in the art would have reasonable expectations that expressing complement factor I or a variant thereof and PACE/furin proteins in the dicistronic AAV vector would result in the obtainment of cleaved recombinant complement factor I protein (mature) or variant thereof from the combined teachings of Wong and Urabe who teach all the necessary methods and compositions needed to do so.
With regards to claim 30, it would have been obvious to one of ordinary skill in the art of protein engineering, to transfect a host cell such as 293 cells taught by Urabe with the modified expression vector arrived at from the combined teachings of Wong and Urabe and culturing the cells in order to express and produce a recombinant mature complement factor I protein or variant thereof. One of ordinary skill in the art would be motivated to do so by the combined teachings of Wong and Urabe in order to produce a mature complement factor I or variant thereof. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Wong and Urabe who provide all the necessary teachings, reagents, and methods to do so.
Therefore, claims 1-2, 4, 8, 30 and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, vol. 32, pg. 379-387, published April 1995: PMID: 7739577) in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150).
Claims 7 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577), hereinafter referred to as Wong, in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150), hereinafter referred to as Urabe, as applied to claim 1 and 30 above, and further in view of Kozak (Journal of Molecular Biology, Vol. 196, pg. 947-950; published August 20, 1987; PMID: 3681984), hereinafter referred to as Kozak.
The teachings of Wong and Urabe as applied to claim 1 and claim 30 are summarized above.
With regards to claim 7 and 32, neither Wong or Urabe specifically teach the presence of a translation initiation sequence positioned downstream of a promoter element and upstream of the nucleic acid molecule encoding the precursor complement factor I protein.
However, Kozak teaches that sequences flanking the AUG initiator codon influence its recognition by eukaryotic ribosomes (see Abstract, pg. 947) and that at least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells. Kozak teaches a representative number of sequences that effect the efficiency of translation (see pg. 949).
It would have been obvious to one of ordinary skill in the art of protein engineering to include a nucleic acid encoding a translation initiation sequence such as ones taught by Kozak upstream the nucleic acid molecule encoding the precursor complement factor I protein and downstream of the promoter element in the expression vector from the combined teachings of Wong and Urabe. One of ordinary skill in the art would be motivated to do so by the teachings of Kozak who teaches sequences that function as protein translation initiation sites that allow for optimal translation and translation efficiency in eukaryotes. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Wong, Urabe, and Kozak who provide all the teachings necessary to do so.
With regards to claim 32, it would have been obvious to one of ordinary skill in the art of protein engineering, to transfect a host cell such as 293 cells taught by Urabe with the modified expression vector arrived at from the combined teachings of Wong Urabe, and Kozak and culturing the cells to produce a recombinant mature complement factor I protein or variant thereof. One of ordinary skill in the art would be motivated to do so by the combined teachings of Wong, Urabe, and Kozak to produce a mature complement factor I or variant thereof using the modified expression vector from the combined teachings of Wong, Urabe, and Kozak. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Wong, Urabe, and Kozak who provide all the necessary teachings, reagents, and methods to do so
Therefore, claims 7 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577) in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150) as applied to claim 1 and claim 30 above, and further in view of Kozak (Journal of Molecular Biology, Vol. 196, pg. 947-950; published August 20, 1987; PMID: 3681984), hereinafter referred to as Kozak.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577), hereinafter referred to as Wong, in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150), hereinafter referred to as Urabe, as applied to claim 8 above, and further in view of Arber et al. (US Patent Application Publication No.: US 2018/0161358 A1; published June 14, 2018), hereinafter referred to as Arber.
The teachings of Wong and Urabe as applied to claim 8 are summarized above.
Neither Wong or Urabe specifically teach that the IRES comprises a nucleic acid sequence as set forth in SEQ ID NO: 9 of the current instant application.
However, Arber teaches a nucleic acid construct which comprises an IRES sequence set forth by SEQ ID NO: 7 (see paragraph 0046) that has 100% sequence identity to SEQ ID NO: 9 of the current instant application (see sequence alignment below):
SEQ ID NO 7
LENGTH: 588
TYPE: DNA
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: IRES
Query Match 100.0%; Score 588; Length 588;
Best Local Similarity 100.0%;
Matches 588; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GCCCCTCTCCCTCCCCCCCCCCTAACGTTACTGGCCGAAGCCGCTTGGAATAAGGCCGGT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GCCCCTCTCCCTCCCCCCCCCCTAACGTTACTGGCCGAAGCCGCTTGGAATAAGGCCGGT 60
Qy 61 GTGCGTTTGTCTATATGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GTGCGTTTGTCTATATGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCC 120
Qy 121 GGAAACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GGAAACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAG 180
Qy 181 GAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGAC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGAC 240
Qy 241 AAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCC 300
Qy 301 TCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCCAGTGCC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCCAGTGCC 360
Qy 361 ACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCTCCTCAAGCGTATTCAACA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCTCCTCAAGCGTATTCAACA 420
Qy 421 AGGGGCTGAAGGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 AGGGGCTGAAGGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGT 480
Qy 481 GCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAAACGTCTAGGCCCCCCGAACCACG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAAACGTCTAGGCCCCCCGAACCACG 540
Qy 541 GGGACGTGGTTTTCCTTTGAAAAACACGATGATAATATGGCCACAACC 588
||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GGGACGTGGTTTTCCTTTGAAAAACACGATGATAATATGGCCACAACC 588
It would have been obvious to one of ordinary skill in the art of protein engineering before the effective filing date of the current instant application to use the IRES sequence taught be Arber as an option for the IRES sequence in the dicistronic expression vector arrived at from the combined teachings of Wong and Urabe. One of ordinary skill in the art would be motivated to do so since Arber teaches a nucleic acid construct for expression of multiple genes comprising an IRES element and the IRES sequence disclosed by Arber could be used as the IRES sequence in the dicistronic construct arrived at from the combined teachings of Wong and Urabe to achieve efficient expression of the complement factor I and PACE/furin proteins. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Wong, Urabe, and Arber who provide all the necessary teachings, methods, compositions, and guidance to do so.
Therefore, claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577) in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150) as applied to claim 8 above, and further in view of Arber et al. (US Patent Application Publication No.: US 2018/0161358 A1; published June 14, 2018).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577), hereinafter referred to as Wong, in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150), hereinafter referred to as Urabe as applied to claim 1 above, and further in view of UniProt Database entry (Q6LAM1_HUMAN; first entry July 05, 2004), hereinafter referred to as Q6LAM1, and further in view of UniProt Database entry (Q6LAM0_HUMAN; first entry July 05, 2004), hereinafter referred to as Q6LAM0.
The teachings of Wong and Urabe as applied to claim 1 are summarized above.
Wong is silent on the specific sequence of the complement factor I protein.
Q6LAM1 teaches a sequence for heavy chain of factor I that comprises SEQ ID NO: 2 (heavy chain) of the instant application (See sequence alignment below):
Query Match 100.0%; Score 1743; Length 321;
Best Local Similarity 100.0%;
Matches 317; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCVCKLPYQCPKNGTAVCATN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 KVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCVCKLPYQCPKNGTAVCATN 60
Qy 61 RRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGNTDSEGIVEVKLVDQDKTM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGNTDSEGIVEVKLVDQDKTM 120
Qy 121 FICKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTECLHVHCRGLETSLAECTF 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FICKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTECLHVHCRGLETSLAECTF 180
Qy 181 TKRRTMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKACDGINDCGDQSDELCCKA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TKRRTMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKACDGINDCGDQSDELCCKA 240
Qy 241 CQGKGFHCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVAQEETEILTADMDAERRRI 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CQGKGFHCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVAQEETEILTADMDAERRRI 300
Qy 301 KSLLPKLSCGVKNRMHI 317
|||||||||||||||||
Db 301 KSLLPKLSCGVKNRMHI 317
Q6LAM0 teaches a sequence for light chain of factor I that comprises SEQ ID NO: 3 (light chain) of the instant application (See sequence alignment below):
Query Match 100.0%; Score 1373; Length 244;
Best Local Similarity 100.0%;
Matches 244; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 IVGGKRAQLGDLPWQVAIKDASGITCGGIYIGGCWILTAAHCLRASKTHRYQIWTTVVDW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 IVGGKRAQLGDLPWQVAIKDASGITCGGIYIGGCWILTAAHCLRASKTHRYQIWTTVVDW 60
Qy 61 IHPDLKRIVIEYVDRIIFHENYNAGTYQNDIALIEMKKDGNKKDCELPRSIPACVPWSPY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IHPDLKRIVIEYVDRIIFHENYNAGTYQNDIALIEMKKDGNKKDCELPRSIPACVPWSPY 120
Qy 121 LFQPNDTCIVSGWGREKDNERVFSLQWGEVKLISNCSKFYGNRFYEKEMECAGTYDGSID 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LFQPNDTCIVSGWGREKDNERVFSLQWGEVKLISNCSKFYGNRFYEKEMECAGTYDGSID 180
Qy 181 ACKGDSGGPLVCMDANNVTYVWGVVSWGENCGKPEFPGVYTKVANYFDWISYHVGRPFIS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ACKGDSGGPLVCMDANNVTYVWGVVSWGENCGKPEFPGVYTKVANYFDWISYHVGRPFIS 240
Qy 241 QYNV 244
||||
Db 241 QYNV 244
It would have been obvious to one of ordinary skill in the art of protein engineering prior to the effective filing date of the current instant application to use the sequence disclosed by Q6LAM1 for the heavy chain component of complement factor I and the sequence disclosed by QLAM0 for the light chain component of complement factor I as the sequence for the complement factor I to be expressed by the expression vector arrived at by the combined teachings of Wong and Urabe. One of ordinary skill in the art of protein engineering would be motivated to do so as both Q6LAM1 and Q6LAM0 disclose sequences for the heavy and light chain components of factor I that can be used as the sequences for the heavy and light chain components of complement factor I taught by Wong. As summarized in the teachings of Wong as applied to claim 1 above, the heavy chain and light chain of factor I are linked by a disulfide bond. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Wong, Urabe, Q6LAM1 and Q6LAM0 who provide all the necessary teachings needed to do so.
Therefore, claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577) in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150) as applied to claim 1 above, and further in view of UniProt Database entry (Q6LAM1_HUMAN; first entry July 05, 2004) and further in view of UniProt Database entry (Q6LAM0_HUMAN; first entry July 05, 2004).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577), hereinafter referred to as Wong, in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150), hereinafter referred to as Urabe, as applied to claim 1 above, and further in view of UniProt Database Entry: (CFAI_HUMAN; first entry: August 13, 1987), hereinafter referred to as CFAI.
The teachings of Wong and Urabe as applied to claim 1 are summarized above.
Wong is silent on the specific sequence of recombinant precursor human complement factor I.
CFAI teaches the sequence of complement factor I that has 100% sequence identity with SEQ ID NO: 1 of the current instant application. (See sequence alignment below).
Query Match 100.0%; Score 3238; Length 583;
Best Local Similarity 100.0%;
Matches 583; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKLLHVFLLFLCFHLRFCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKLLHVFLLFLCFHLRFCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCV 60
Qy 61 CKLPYQCPKNGTAVCATNRRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CKLPYQCPKNGTAVCATNRRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGN 120
Qy 121 TDSEGIVEVKLVDQDKTMFICKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TDSEGIVEVKLVDQDKTMFICKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTE 180
Qy 181 CLHVHCRGLETSLAECTFTKRRTMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CLHVHCRGLETSLAECTFTKRRTMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKA 240
Qy 241 CDGINDCGDQSDELCCKACQGKGFHCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CDGINDCGDQSDELCCKACQGKGFHCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVT 300
Qy 301 QEETEILTADMDAERRRIKSLLPKLSCGVKNRMHIRRKRIVGGKRAQLGDLPWQVAIKDA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QEETEILTADMDAERRRIKSLLPKLSCGVKNRMHIRRKRIVGGKRAQLGDLPWQVAIKDA 360
Qy 361 SGITCGGIYIGGCWILTAAHCLRASKTHRYQIWTTVVDWIHPDLKRIVIEYVDRIIFHEN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 SGITCGGIYIGGCWILTAAHCLRASKTHRYQIWTTVVDWIHPDLKRIVIEYVDRIIFHEN 420
Qy 421 YNAGTYQNDIALIEMKKDGNKKDCELPRSIPACVPWSPYLFQPNDTCIVSGWGREKDNER 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YNAGTYQNDIALIEMKKDGNKKDCELPRSIPACVPWSPYLFQPNDTCIVSGWGREKDNER 480
Qy 481 VFSLQWGEVKLISNCSKFYGNRFYEKEMECAGTYDGSIDACKGDSGGPLVCMDANNVTYV 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 VFSLQWGEVKLISNCSKFYGNRFYEKEMECAGTYDGSIDACKGDSGGPLVCMDANNVTYV 540
Qy 541 WGVVSWGENCGKPEFPGVYTKVANYFDWISYHVGRPFISQYNV 583
|||||||||||||||||||||||||||||||||||||||||||
Db 541 WGVVSWGENCGKPEFPGVYTKVANYFDWISYHVGRPFISQYNV 583
It would have been obvious to one of ordinary skill in the art of protein engineering prior to the effective filing date of the current instant application to use the sequence disclosed by CAF as the sequence for the complement factor I to be expressed by the expression vector arrived at by from the combined teachings of Wong and Urabe. One of ordinary skill in the art of protein engineering would be motivated to do so as CAFI discloses a sequence for complement factor I that can be used as the sequence for the complement factor I to be expressed in the expression vector taught by Wong. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Wong, Urabe, CAFI who provide all the necessary teachings needed to do so.
Therefore, claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577) in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150) as applied to claim 1 above, and further in view of UniProt Database Entry: (CFAI_HUMAN; first entry: August 13, 1987).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577), hereinafter referred to as Wong, in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150), hereinafter referred to as Urabe, as applied to claim 1 above, and further in view of UniProt Database Entry: (FURIN_HUMAN; first entry July 01, 1989), hereinafter referred to as FURIN.
The teachings of Wong and Urabe as applied to claim 1 are summarized above.
Wong is silent of the specific sequence of the PACE/FURIN.
FURIN teaches a sequence for Paired basic amino acid residue-cleaning enzyme that has 100% sequence identity to SEQ ID NO: 5 of the current instant application (see sequence alignment below).
Query Match 100.0%; Score 4260; Length 794;
Best Local Similarity 100.0%;
Matches 794; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MELRPWLLWVVAATGTLVLLAADAQGQKVFTNTWAVRIPGGPAVANSVARKHGFLNLGQI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MELRPWLLWVVAATGTLVLLAADAQGQKVFTNTWAVRIPGGPAVANSVARKHGFLNLGQI 60
Qy 61 FGDYYHFWHRGVTKRSLSPHRPRHSRLQREPQVQWLEQQVAKRRTKRDVYQEPTDPKFPQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FGDYYHFWHRGVTKRSLSPHRPRHSRLQREPQVQWLEQQVAKRRTKRDVYQEPTDPKFPQ 120
Qy 121 QWYLSGVTQRDLNVKAAWAQGYTGHGIVVSILDDGIEKNHPDLAGNYDPGASFDVNDQDP 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QWYLSGVTQRDLNVKAAWAQGYTGHGIVVSILDDGIEKNHPDLAGNYDPGASFDVNDQDP 180
Qy 181 DPQPRYTQMNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGEVTDAVEARSL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DPQPRYTQMNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGEVTDAVEARSL 240
Qy 241 GLNPNHIHIYSASWGPEDDGKTVDGPARLAEEAFFRGVSQGRGGLGSIFVWASGNGGREH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GLNPNHIHIYSASWGPEDDGKTVDGPARLAEEAFFRGVSQGRGGLGSIFVWASGNGGREH 300
Qy 301 DSCNCDGYTNSIYTLSISSATQFGNVPWYSEACSSTLATTYSSGNQNEKQIVTTDLRQKC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DSCNCDGYTNSIYTLSISSATQFGNVPWYSEACSSTLATTYSSGNQNEKQIVTTDLRQKC 360
Qy 361 TESHTGTSASAPLAAGIIALTLEANKNLTWRDMQHLVVQTSKPAHLNANDWATNGVGRKV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 TESHTGTSASAPLAAGIIALTLEANKNLTWRDMQHLVVQTSKPAHLNANDWATNGVGRKV 420
Qy 421 SHSYGYGLLDAGAMVALAQNWTTVAPQRKCIIDILTEPKDIGKRLEVRKTVTACLGEPNH 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 SHSYGYGLLDAGAMVALAQNWTTVAPQRKCIIDILTEPKDIGKRLEVRKTVTACLGEPNH 480
Qy 481 ITRLEHAQARLTLSYNRRGDLAIHLVSPMGTRSTLLAARPHDYSADGFNDWAFMTTHSWD 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 ITRLEHAQARLTLSYNRRGDLAIHLVSPMGTRSTLLAARPHDYSADGFNDWAFMTTHSWD 540
Qy 541 EDPSGEWVLEIENTSEANNYGTLTKFTLVLYGTAPEGLPVPPESSGCKTLTSSQACVVCE 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 EDPSGEWVLEIENTSEANNYGTLTKFTLVLYGTAPEGLPVPPESSGCKTLTSSQACVVCE 600
Qy 601 EGFSLHQKSCVQHCPPGFAPQVLDTHYSTENDVETIRASVCAPCHASCATCQGPALTDCL 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 EGFSLHQKSCVQHCPPGFAPQVLDTHYSTENDVETIRASVCAPCHASCATCQGPALTDCL 660
Qy 661 SCPSHASLDPVEQTCSRQSQSSRESPPQQQPPRLPPEVEAGQRLRAGLLPSHLPEVVAGL 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 SCPSHASLDPVEQTCSRQSQSSRESPPQQQPPRLPPEVEAGQRLRAGLLPSHLPEVVAGL 720
Qy 721 SCAFIVLVFVTVFLVLQLRSGFSFRGVKVYTMDRGLISYKGLPPEAWQEECPSDSEEDEG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 SCAFIVLVFVTVFLVLQLRSGFSFRGVKVYTMDRGLISYKGLPPEAWQEECPSDSEEDEG 780
Qy 781 RGERTAFIKDQSAL 794
||||||||||||||
Db 781 RGERTAFIKDQSAL 794
It would have been obvious to one of ordinary skill in the art of protein engineering prior to the effective filing date of the current instant application to use the sequence disclosed by FURIN as the sequence for the PACE/furin to be expressed by the expression vector arrived at from the combined teachings of Wong and Urabe. One of ordinary skill in the art of protein engineering would be motivated to do so as FURIN discloses the sequence for PACE that can be used as the sequence for the PACE/furin protein to be expressed in the expression vector arrived at from teachings of Wong and Urabe. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Wong, Urabe, FURIN who provide all the necessary teachings needed to do so.
Therefore, claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577) in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150) as applied to claim 1 above, and further in view of UniProt Database Entry: (FURIN_HUMAN; first entry July 01, 1989).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577), hereinafter referred to as Wong, in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150), hereinafter referred to as Urabe, as applied to claim 1 above, and further in view of Groendahl et al. (US Patent Application Publication No.: US 2019/0255193 A1; published August 22, 2019), hereinafter referred to as Groendahl.
The teachings of Wong and Urabe as applied to claim 1 are summarized above.
Neither Wong or Urabe specifically teach a nucleic acid sequence as set forth in SEQ ID NO: 10 of the current instant application.
Groendahl teaches an AAV vector comprising a nucleotide sequence encoding Factor I (see abstract) and further teaches a nucleotide sequence encoding factor I (SEQ ID NO: 2) that has 100% sequence identity with SEQ ID NO: 10 of the current instant application (see paragraphs 0014-0017 and sequence alignment below).
Query Match 100.0%; Score 1752; Length 1752;
Best Local Similarity 100.0%;
Matches 1752; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGAAGCTTCTTCATGTTTTCCTGTTATTTCTGTGCTTCCACTTAAGGTTTTGCAAGGTC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGAAGCTTCTTCATGTTTTCCTGTTATTTCTGTGCTTCCACTTAAGGTTTTGCAAGGTC 60
Qy 61 ACTTATACATCTCAAGAGGATCTGGTGGAGAAAAAGTGCTTAGCAAAAAAATATACTCAC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ACTTATACATCTCAAGAGGATCTGGTGGAGAAAAAGTGCTTAGCAAAAAAATATACTCAC 120
Qy 121 CTCTCCTGCGATAAAGTCTTCTGCCAGCCATGGCAGAGATGCATTGAGGGCACCTGTGTT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CTCTCCTGCGATAAAGTCTTCTGCCAGCCATGGCAGAGATGCATTGAGGGCACCTGTGTT 180
Qy 181 TGTAAACTACCGTATCAGTGCCCAAAGAATGGCACTGCAGTGTGTGCAACTAACAGGAGA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TGTAAACTACCGTATCAGTGCCCAAAGAATGGCACTGCAGTGTGTGCAACTAACAGGAGA 240
Qy 241 AGCTTCCCAACATACTGTCAACAAAAGAGTTTGGAATGTCTTCATCCAGGGACAAAGTTT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AGCTTCCCAACATACTGTCAACAAAAGAGTTTGGAATGTCTTCATCCAGGGACAAAGTTT 300
Qy 301 TTAAATAACGGAACATGCACAGCCGAAGGAAAGTTTAGTGTTTCCTTGAAGCATGGAAAT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TTAAATAACGGAACATGCACAGCCGAAGGAAAGTTTAGTGTTTCCTTGAAGCATGGAAAT 360
Qy 361 ACAGATTCAGAGGGAATAGTTGAAGTAAAACTTGTGGACCAAGATAAGACAATGTTCATA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ACAGATTCAGAGGGAATAGTTGAAGTAAAACTTGTGGACCAAGATAAGACAATGTTCATA 420
Qy 421 TGCAAAAGCAGCTGGAGCATGAGGGAAGCCAACGTGGCCTGCCTTGACCTTGGGTTTCAA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 TGCAAAAGCAGCTGGAGCATGAGGGAAGCCAACGTGGCCTGCCTTGACCTTGGGTTTCAA 480
Qy 481 CAAGGTGCTGATACTCAAAGAAGGTTTAAGTTGTCTGATCTCTCTATAAATTCCACTGAA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CAAGGTGCTGATACTCAAAGAAGGTTTAAGTTGTCTGATCTCTCTATAAATTCCACTGAA 540
Qy 541 TGTCTACATGTGCATTGCCGAGGATTAGAGACCAGTTTGGCTGAATGTACTTTTACTAAG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 TGTCTACATGTGCATTGCCGAGGATTAGAGACCAGTTTGGCTGAATGTACTTTTACTAAG 600
Qy 601 AGAAGAACTATGGGTTACCAGGATTTCGCTGATGTGGTTTGTTATACACAGAAAGCAGAT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 AGAAGAACTATGGGTTACCAGGATTTCGCTGATGTGGTTTGTTATACACAGAAAGCAGAT 660
Qy 661 TCTCCAATGGATGACTTCTTTCAGTGTGTGAATGGGAAATACATTTCTCAGATGAAAGCC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 TCTCCAATGGATGACTTCTTTCAGTGTGTGAATGGGAAATACATTTCTCAGATGAAAGCC 720
Qy 721 TGTGATGGTATCAATGATTGTGGAGACCAAAGTGATGAACTGTGTTGTAAAGCATGCCAA 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 TGTGATGGTATCAATGATTGTGGAGACCAAAGTGATGAACTGTGTTGTAAAGCATGCCAA 780
Qy 781 GGCAAAGGCTTCCATTGCAAATCGGGTGTTTGCATTCCAAGCCAGTATCAATGCAATGGT 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GGCAAAGGCTTCCATTGCAAATCGGGTGTTTGCATTCCAAGCCAGTATCAATGCAATGGT 840
Qy 841 GAGGTGGACTGCATTACAGGGGAAGATGAAGTTGGCTGTGCAGGCTTTGCATCTGTGGCT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 GAGGTGGACTGCATTACAGGGGAAGATGAAGTTGGCTGTGCAGGCTTTGCATCTGTGGCT 900
Qy 901 CAAGAAGAAACAGAAATTTTGACTGCTGACATGGATGCAGAAAGAAGACGGATAAAATCA 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 CAAGAAGAAACAGAAATTTTGACTGCTGACATGGATGCAGAAAGAAGACGGATAAAATCA 960
Qy 961 TTATTACCTAAACTATCTTGTGGAGTTAAAAACAGAATGCACATTCGAAGGAAACGAATT 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 TTATTACCTAAACTATCTTGTGGAGTTAAAAACAGAATGCACATTCGAAGGAAACGAATT 1020
Qy 1021 GTGGGAGGAAAGCGAGCACAACTGGGAGACCTCCCATGGCAGGTGGCAATTAAGGATGCC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GTGGGAGGAAAGCGAGCACAACTGGGAGACCTCCCATGGCAGGTGGCAATTAAGGATGCC 1080
Qy 1081 AGTGGAATCACCTGTGGGGGAATTTATATTGGTGGCTGTTGGATTCTGACTGCTGCACAT 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 AGTGGAATCACCTGTGGGGGAATTTATATTGGTGGCTGTTGGATTCTGACTGCTGCACAT 1140
Qy 1141 TGTCTCAGAGCCAGTAAAACTCATCGTTACCAAATATGGACAACAGTAGTAGACTGGATA 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 TGTCTCAGAGCCAGTAAAACTCATCGTTACCAAATATGGACAACAGTAGTAGACTGGATA 1200
Qy 1201 CACCCCGACCTTAAACGTATAGTAATTGAATACGTGGATAGAATTATTTTCCATGAAAAC 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 CACCCCGACCTTAAACGTATAGTAATTGAATACGTGGATAGAATTATTTTCCATGAAAAC 1260
Qy 1261 TACAATGCAGGCACTTACCAAAATGACATCGCTTTGATTGAAATGAAAAAAGACGGAAAC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 TACAATGCAGGCACTTACCAAAATGACATCGCTTTGATTGAAATGAAAAAAGACGGAAAC 1320
Qy 1321 AAAAAAGATTGTGAGCTGCCTCGTTCCATCCCTGCCTGTGTCCCCTGGTCTCCTTACCTA 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 AAAAAAGATTGTGAGCTGCCTCGTTCCATCCCTGCCTGTGTCCCCTGGTCTCCTTACCTA 1380
Qy 1381 TTCCAACCTAATGATACATGCATCGTTTCTGGCTGGGGACGAGAAAAAGATAACGAAAGA 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 TTCCAACCTAATGATACATGCATCGTTTCTGGCTGGGGACGAGAAAAAGATAACGAAAGA 1440
Qy 1441 GTCTTTTCACTTCAGTGGGGTGAAGTTAAACTAATAAGCAACTGCTCTAAGTTTTACGGA 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 GTCTTTTCACTTCAGTGGGGTGAAGTTAAACTAATAAGCAACTGCTCTAAGTTTTACGGA 1500
Qy 1501 AATCGTTTCTATGAAAAAGAAATGGAATGTGCAGGTACATATGATGGTTCCATCGATGCC 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 AATCGTTTCTATGAAAAAGAAATGGAATGTGCAGGTACATATGATGGTTCCATCGATGCC 1560
Qy 1561 TGTAAAGGGGACTCTGGAGGCCCCTTAGTCTGTATGGATGCCAACAATGTGACTTATGTC 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 TGTAAAGGGGACTCTGGAGGCCCCTTAGTCTGTATGGATGCCAACAATGTGACTTATGTC 1620
Qy 1621 TGGGGTGTTGTGAGTTGGGGGGAAAACTGTGGAAAACCAGAGTTCCCAGGTGTTTACACC 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 TGGGGTGTTGTGAGTTGGGGGGAAAACTGTGGAAAACCAGAGTTCCCAGGTGTTTACACC 1680
Qy 1681 AAAGTGGCCAATTATTTTGACTGGATTAGCTACCATGTAGGAAGGCCTTTTATTTCTCAG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 AAAGTGGCCAATTATTTTGACTGGATTAGCTACCATGTAGGAAGGCCTTTTATTTCTCAG 1740
Qy 1741 TACAATGTATAA 1752
||||||||||||
Db 1741 TACAATGTATAA 1752
It would have been obvious to one of ordinary skill in the art of protein engineering prior to the effective filing date of the current instant application to use the nucleotide sequence taught by Groendahl as the nucleotide sequence for the expression of complement factor I in the expression vector arrived at from the combined teachings of Wong and Urabe. One of ordinary skill in the art of protein engineering would be motivated to do so as Groendahl discloses a nucleotide sequence for complement factor I that can be used in the expression vector arrived at from the teachings of Wong and Urabe to achieve the expression of complement factor I. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Wong, Urabe, Groendahl who provide all the necessary teachings needed to do so.
Therefore, claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577) in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150) as applied to claim 1 above, and further in view of Groendahl et al. (US Patent Application Publication No.: US 2019/0255193 A1; published August 22, 2019).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577), hereinafter referred to as Wong, in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150), hereinafter referred to as Urabe, as applied to claim 1 above, and further in view of Peters et al. (United States Patent Application Publication No.: US 2013/0281671A1; published October 24, 2013), hereinafter referred to as Peters.
The teachings of Wong and Urabe as applied to claim 1 are summarized above.
Neither Wong or Urabe specifically teach that the expression vector comprises a nucleic acid sequence having at least 90% sequence identity to the nucleic acid sequence as set forth in SEQ ID No. 8 of the current instant application.
Peters teaches a nucleotide sequence (SEQ ID NO: 11) that encodes a Furin, paired basic amino acid residue cleaving enzyme (PACE), that has 100% sequence identity with SEQ ID NO: 8 of the current instant application (see paragraph 0103 and see sequence alignment below).
Query Match 100.0%; Score 2385; Length 2385;
Best Local Similarity 100.0%;
Matches 2385; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGGAGCTGAGGCCCTGGTTGCTATGGGTGGTAGCAGCAACAGGAACCTTGGTCCTGCTA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGGAGCTGAGGCCCTGGTTGCTATGGGTGGTAGCAGCAACAGGAACCTTGGTCCTGCTA 60
Qy 61 GCAGCTGATGCTCAGGGCCAGAAGGTCTTCACCAACACGTGGGCTGTGCGCATCCCTGGA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GCAGCTGATGCTCAGGGCCAGAAGGTCTTCACCAACACGTGGGCTGTGCGCATCCCTGGA 120
Qy 121 GGCCCAGCGGTGGCCAACAGTGTGGCACGGAAGCATGGGTTCCTCAACCTGGGCCAGATC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GGCCCAGCGGTGGCCAACAGTGTGGCACGGAAGCATGGGTTCCTCAACCTGGGCCAGATC 180
Qy 181 TTCGGGGACTATTACCACTTCTGGCATCGAGGAGTGACGAAGCGGTCCCTGTCGCCTCAC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TTCGGGGACTATTACCACTTCTGGCATCGAGGAGTGACGAAGCGGTCCCTGTCGCCTCAC 240
Qy 241 CGCCCGCGGCACAGCCGGCTGCAGAGGGAGCCTCAAGTACAGTGGCTGGAACAGCAGGTG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CGCCCGCGGCACAGCCGGCTGCAGAGGGAGCCTCAAGTACAGTGGCTGGAACAGCAGGTG 300
Qy 301 GCAAAGCGACGGACTAAACGGGACGTGTACCAGGAGCCCACAGACCCCAAGTTTCCTCAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GCAAAGCGACGGACTAAACGGGACGTGTACCAGGAGCCCACAGACCCCAAGTTTCCTCAG 360
Qy 361 CAGTGGTACCTGTCTGGTGTCACTCAGCGGGACCTGAATGTGAAGGCGGCCTGGGCGCAG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CAGTGGTACCTGTCTGGTGTCACTCAGCGGGACCTGAATGTGAAGGCGGCCTGGGCGCAG 420
Qy 421 GGCTACACAGGGCACGGCATTGTGGTCTCCATTCTGGACGATGGCATCGAGAAGAACCAC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GGCTACACAGGGCACGGCATTGTGGTCTCCATTCTGGACGATGGCATCGAGAAGAACCAC 480
Qy 481 CCGGACTTGGCAGGCAATTATGATCCTGGGGCCAGTTTTGATGTCAATGACCAGGACCCT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CCGGACTTGGCAGGCAATTATGATCCTGGGGCCAGTTTTGATGTCAATGACCAGGACCCT 540
Qy 541 GACCCCCAGCCTCGGTACACACAGATGAATGACAACAGGCACGGCACACGGTGTGCGGGG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GACCCCCAGCCTCGGTACACACAGATGAATGACAACAGGCACGGCACACGGTGTGCGGGG 600
Qy 601 GAAGTGGCTGCGGTGGCCAACAACGGTGTCTGTGGTGTAGGTGTGGCCTACAACGCCCGC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GAAGTGGCTGCGGTGGCCAACAACGGTGTCTGTGGTGTAGGTGTGGCCTACAACGCCCGC 660
Qy 661 ATTGGAGGGGTGCGCATGCTGGATGGCGAGGTGACAGATGCAGTGGAGGCACGCTCGCTG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 ATTGGAGGGGTGCGCATGCTGGATGGCGAGGTGACAGATGCAGTGGAGGCACGCTCGCTG 720
Qy 721 GGCCTGAACCCCAACCACATCCACATCTACAGTGCCAGCTGGGGCCCCGAGGATGACGGC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GGCCTGAACCCCAACCACATCCACATCTACAGTGCCAGCTGGGGCCCCGAGGATGACGGC 780
Qy 781 AAGACAGTGGATGGGCCAGCCCGCCTCGCCGAGGAGGCCTTCTTCCGTGGGGTTAGCCAG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 AAGACAGTGGATGGGCCAGCCCGCCTCGCCGAGGAGGCCTTCTTCCGTGGGGTTAGCCAG 840
Qy 841 GGCCGAGGGGGGCTGGGCTCCATCTTTGTCTGGGCCTCGGGGAACGGGGGCCGGGAACAT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 GGCCGAGGGGGGCTGGGCTCCATCTTTGTCTGGGCCTCGGGGAACGGGGGCCGGGAACAT 900
Qy 901 GACAGCTGCAACTGCGACGGCTACACCAACAGTATCTACACGCTGTCCATCAGCAGCGCC 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GACAGCTGCAACTGCGACGGCTACACCAACAGTATCTACACGCTGTCCATCAGCAGCGCC 960
Qy 961 ACGCAGTTTGGCAACGTGCCGTGGTACAGCGAGGCCTGCTCGTCCACACTGGCCACGACC 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 ACGCAGTTTGGCAACGTGCCGTGGTACAGCGAGGCCTGCTCGTCCACACTGGCCACGACC 1020
Qy 1021 TACAGCAGTGGCAACCAGAATGAGAAGCAGATCGTGACGACTGACTTGCGGCAGAAGTGC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 TACAGCAGTGGCAACCAGAATGAGAAGCAGATCGTGACGACTGACTTGCGGCAGAAGTGC 1080
Qy 1081 ACGGAGTCTCACACGGGCACCTCAGCCTCTGCCCCCTTAGCAGCCGGCATCATTGCTCTC 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 ACGGAGTCTCACACGGGCACCTCAGCCTCTGCCCCCTTAGCAGCCGGCATCATTGCTCTC 1140
Qy 1141 ACCCTGGAGGCCAATAAGAACCTCACATGGCGGGACATGCAACACCTGGTGGTACAGACC 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 ACCCTGGAGGCCAATAAGAACCTCACATGGCGGGACATGCAACACCTGGTGGTACAGACC 1200
Qy 1201 TCGAAGCCAGCCCACCTCAATGCCAACGACTGGGCCACCAATGGTGTGGGCCGGAAAGTG 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 TCGAAGCCAGCCCACCTCAATGCCAACGACTGGGCCACCAATGGTGTGGGCCGGAAAGTG 1260
Qy 1261 AGCCACTCATATGGCTACGGGCTTTTGGACGCAGGCGCCATGGTGGCCCTGGCCCAGAAT 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 AGCCACTCATATGGCTACGGGCTTTTGGACGCAGGCGCCATGGTGGCCCTGGCCCAGAAT 1320
Qy 1321 TGGACCACAGTGGCCCCCCAGCGGAAGTGCATCATCGACATCCTCACCGAGCCCAAAGAC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 TGGACCACAGTGGCCCCCCAGCGGAAGTGCATCATCGACATCCTCACCGAGCCCAAAGAC 1380
Qy 1381 ATCGGGAAACGGCTCGAGGTGCGGAAGACCGTGACCGCGTGCCTGGGCGAGCCCAACCAC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 ATCGGGAAACGGCTCGAGGTGCGGAAGACCGTGACCGCGTGCCTGGGCGAGCCCAACCAC 1440
Qy 1441 ATCACTCGGCTGGAGCACGCTCAGGCGCGGCTCACCCTGTCCTATAATCGCCGTGGCGAC 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 ATCACTCGGCTGGAGCACGCTCAGGCGCGGCTCACCCTGTCCTATAATCGCCGTGGCGAC 1500
Qy 1501 CTGGCCATCCACCTGGTCAGCCCCATGGGCACCCGCTCCACCCTGCTGGCAGCCAGGCCA 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 CTGGCCATCCACCTGGTCAGCCCCATGGGCACCCGCTCCACCCTGCTGGCAGCCAGGCCA 1560
Qy 1561 CATGACTACTCCGCAGATGGGTTTAATGACTGGGCCTTCATGACAACTCATTCCTGGGAT 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 CATGACTACTCCGCAGATGGGTTTAATGACTGGGCCTTCATGACAACTCATTCCTGGGAT 1620
Qy 1621 GAGGATCCCTCTGGCGAGTGGGTCCTAGAGATTGAAAACACCAGCGAAGCCAACAACTAT 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 GAGGATCCCTCTGGCGAGTGGGTCCTAGAGATTGAAAACACCAGCGAAGCCAACAACTAT 1680
Qy 1681 GGGACGCTGACCAAGTTCACCCTCGTACTCTATGGCACCGCCCCTGAGGGGCTGCCCGTA 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 GGGACGCTGACCAAGTTCACCCTCGTACTCTATGGCACCGCCCCTGAGGGGCTGCCCGTA 1740
Qy 1741 CCTCCAGAAAGCAGTGGCTGCAAGACCCTCACGTCCAGTCAGGCCTGTGTGGTGTGCGAG 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 CCTCCAGAAAGCAGTGGCTGCAAGACCCTCACGTCCAGTCAGGCCTGTGTGGTGTGCGAG 1800
Qy 1801 GAAGGCTTCTCCCTGCACCAGAAGAGCTGTGTCCAGCACTGCCCTCCAGGCTTCGCCCCC 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 GAAGGCTTCTCCCTGCACCAGAAGAGCTGTGTCCAGCACTGCCCTCCAGGCTTCGCCCCC 1860
Qy 1861 CAAGTCCTCGATACGCACTATAGCACCGAGAATGACGTGGAGACCATCCGGGCCAGCGTC 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 CAAGTCCTCGATACGCACTATAGCACCGAGAATGACGTGGAGACCATCCGGGCCAGCGTC 1920
Qy 1921 TGCGCCCCCTGCCACGCCTCATGTGCCACATGCCAGGGGCCGGCCCTGACAGACTGCCTC 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 TGCGCCCCCTGCCACGCCTCATGTGCCACATGCCAGGGGCCGGCCCTGACAGACTGCCTC 1980
Qy 1981 AGCTGCCCCAGCCACGCCTCCTTGGACCCTGTGGAGCAGACTTGCTCCCGGCAAAGCCAG 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1981 AGCTGCCCCAGCCACGCCTCCTTGGACCCTGTGGAGCAGACTTGCTCCCGGCAAAGCCAG 2040
Qy 2041 AGCAGCCGAGAGTCCCCGCCACAGCAGCAGCCACCTCGGCTGCCCCCGGAGGTGGAGGCG 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 AGCAGCCGAGAGTCCCCGCCACAGCAGCAGCCACCTCGGCTGCCCCCGGAGGTGGAGGCG 2100
Qy 2101 GGGCAACGGCTGCGGGCAGGGCTGCTGCCCTCACACCTGCCTGAGGTGGTGGCCGGCCTC 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2101 GGGCAACGGCTGCGGGCAGGGCTGCTGCCCTCACACCTGCCTGAGGTGGTGGCCGGCCTC 2160
Qy 2161 AGCTGCGCCTTCATCGTGCTGGTCTTCGTCACTGTCTTCCTGGTCCTGCAGCTGCGCTCT 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2161 AGCTGCGCCTTCATCGTGCTGGTCTTCGTCACTGTCTTCCTGGTCCTGCAGCTGCGCTCT 2220
Qy 2221 GGCTTTAGTTTTCGGGGGGTGAAGGTGTACACCATGGACCGTGGCCTCATCTCCTACAAG 2280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2221 GGCTTTAGTTTTCGGGGGGTGAAGGTGTACACCATGGACCGTGGCCTCATCTCCTACAAG 2280
Qy 2281 GGGCTGCCCCCTGAAGCCTGGCAGGAGGAGTGCCCGTCTGACTCAGAAGAGGACGAGGGC 2340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2281 GGGCTGCCCCCTGAAGCCTGGCAGGAGGAGTGCCCGTCTGACTCAGAAGAGGACGAGGGC 2340
Qy 2341 CGGGGCGAGAGGACCGCCTTTATCAAAGACCAGAGCGCCCTCTGA 2385
|||||||||||||||||||||||||||||||||||||||||||||
Db 2341 CGGGGCGAGAGGACCGCCTTTATCAAAGACCAGAGCGCCCTCTGA 2385
It would have been obvious to one of ordinary skill in the art of protein engineering prior to the effective filing date of the current instant application to use the nucleotide sequence taught by Peters as the nucleotide sequence for the expression of PACE/furin in the expression vector arrived at from the combined teachings of Wong and Urabe. One of ordinary skill in the art of protein engineering would be motivated to do so as Peters discloses a nucleotide sequence for PACE/furin that can be used in the expression vector arrived at from the teachings of Wong and Urabe to achieve the expression of PACE/furin. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Wong, Urabe, Peters who provide all the necessary teachings needed to do so.
Therefore, claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (Molecular Immunology, Vol. 32, pg. 379-387, published April 1995: PMID: 7739577) in view of Urabe et al. (Gene, Vol. 200, pg. 157-162, published October 24, 1997; PMID: 9373150) as applied to claim 1 above, and further in view of Peters et al. (United States Patent Application Publication No.: US 2013/0281671A1; published October 24, 2013).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE T LOUNTOS whose telephone number is (571)272-0502. The examiner can normally be reached Monday-Friday 8:00 am - 5:00 pm.
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/GEORGE THEMISTOCLIS LOUNTOS/ Examiner, Art Unit 1652
/ROBERT B MONDESI/ Supervisory Patent Examiner, Art Unit 1652
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