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 .
Priority
This application was filed on and is a U.S. national Stage application under 35 U.S.C. 371 of International Patent Application No. PCT/US2020/025129 filed 03/27/2020, which claims the benefit of the priority of US Provisional application 62/824,671 filed 03/27/2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Claims 6, 9, 18-44 are withdrawn from further consideration pursuant to 37 CFR
1.142(b) as being drawn to a nonelected Group II-VI and based on the elected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/10/2025. Applicant’s election without traverse of Group I drawn to a production system, in the reply filed on 01/10/2025 is acknowledged. Applicant further elected the species of SEQ ID NO: 25, 28, and 30. As a result, claims 6 and 18 are withdrawn from consideration.
Claim Status
Claims 1, 3, 5-6, are amended. Claims 2, 7-9, 14-44 are canceled. Claims 1,3-5, 10-13, and 45-49 are being examined on the merits in this office action.
Claim Rejections - Withdrawn
The rejection of claims 1, 3-5, 10-13, 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of the claim amendments.
The rejection of claims 1-2, 7, 10-13 under 35 U.S.C. 102(a)(1) as being anticipated by Kivirikko et al . (US20020142391A1 – hereinafter “Kivirikko”) is withdrawn in view of the claim amendments.
The rejection of claims 1-5, 7-8, and 10-17 are rejected under 35 U.S.C. 103 as being unpatentable over Viswanathan et al. (US 2015/0011733A1 – herein after “Viswanathan”) as evidenced by Gorres et al. (Crit Rev Biochem Mol Biol. 2010 Apr;45(2):106–124) in view of Chou et al. (US20070087405A1 – hereinafter “Chou”) and Jin et al. (US20110178157A1 – hereinafter “Jin”) is withdrawn in view of the claim amendments.
Claim Rejections - 35 USC § 112 - New
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, 3-4, 10-13, and 46 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. This is a NEW MATTER rejection.
The response filed 09/08/2025 has introduced NEW MATTER into the claims. The newly added/amended Claim(s) 1 recites “having at least 90% sequence identity to a wild-type alpha polypeptide of prolyl 4-hydroxylase” and “having at least 90% sequence identity to a wild-type beta polypeptide of prolyl 4-hydroxylase” and “having at least 90% sequence identity to a wild-type heat shock protein”. The response did not specifically and adequately point out where support for newly added/amended Claim(s) could be found in the originally filed disclosure.
Although the PTO has the initial burden of presenting evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims, when filing an amendment an applicant should show support in the original disclosure for new or amended claims. See MPEP 714.02 and 2163.06 (“Applicant should therefore specifically point out the support for any amendments made to the disclosure.”).
The amended claims now recites limitations, which were not clearly disclosed in the specification as filed, and now change the scope of the instant disclosure as filed. Such limitations recited in newly amended claim, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C 112. The claims now recite having at least 90% sequence identity to a wild-type alpha and beta polypeptide of prolyl 4-hydroxylase. This limitation is not found in the disclosure. Applicant is required to provide sufficient written support for the limitations recited in the present claims in the specification, or claims as-filed, or remove these limitations from the claims in response to this Office Action.
Claim Rejections - 35 USC § 103 - New
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim Interpretation
The instant claims recite a “production system”. The instant disclosure defines a production system as a “system that can produce a polypeptide of interest…”, and “…comprise cells that express the polypeptide of interest…”, specifically, instant production system “…comprises host cells that are engineered to express rCol7…”.
Thus, any prior art that teaches host cells for use to produce or express rCol7, would read on the instant claims.
Claims 1, 3-4, 10-13, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Kivirikko et al . (US20020142391A1 – hereinafter “Kivirikko”) in view of Viswanathan et al. (US 2015/0011733A1 – herein after “Viswanathan”).
Kivirikko teaches a system for producing a collagen polypeptide, wherein said collagen is selected from the group comprising collagen types including collagen 7 comprising culturing a host cell, wherein said host cell has been infected, transfected or transformed with (i) a first expression vector comprising a polynucleotide molecule having a nucleic acid sequence which encodes a collagen subunit; and (ii) a second expression vector comprising a polynucleotide molecule having a nucleic acid sequence which encodes at least one collagen post-translational enzyme or subunit thereof (claim 1), wherein the collagen post-translational enzyme is the an alpha subunit of prolyl-4-hydroxylase and a beta subunit of prolyl-4-hydroxylase (claims 5-6), wherein the collagen is human recombinant collagen (Abstract, [0003]).
Kivirikko teaches all the steps of the instant claim one and generally teaches that the vector comprises polynucleotide but doesn’t explicitly teach exogenous polynucleotide. However, the use of exogenous polynucleotide is known in the art as taught by Viswanathan et al.
Viswanathan teaches a method that comprises providing a cell, e.g., a mammalian cell, e.g., a CHO or HEK cell, genetically modified to express collagen 7, or a functional fragment thereof, and, optionally, one or more polypeptides, e.g., one or more polypeptides that increase collagen 7 production in the cell such as prolyl hydroxylase, culturing the cell under conditions sufficient for the production of collagen 7, or functional fragment thereof, thereby making collagen 7, or a functional fragment thereof [0004-0006, 0034-0038]. Viswanathan teaches that the cell comprises exogenously introduced nucleic acids that encode the collagen 7 and the prolyl hydroxylase (claims 4-6; [0078]). Viswanathan teaches the polynucleotide sequence of human collagen 7 of SEQ ID NO: 1 [0062] which is identical to the instant SEQ ID NO: 25
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Kivirikko and use exogenous polynucleotides as taught by Viswanathan so as to optimize production of the recombinant collagen 7, or a functional fragment thereof [0078]. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using exogenous polynucleotides as taught by Viswanathan so as to optimize the production of collagen polypeptide. The disclosure render obvious claim 1.
Regarding claim 3, Kivirikko teaches a system for producing a collagen polypeptide, wherein said collagen is selected from the group comprising collagen types including collagen 7 comprising culturing a host cell, wherein said host cell has been infected, transfected or transformed with (i) a first expression vector comprising a polynucleotide molecule having a nucleic acid sequence which encodes a collagen subunit; and (ii) a second expression vector comprising a polynucleotide molecule having a nucleic acid sequence which encodes at least one collagen post-translational enzyme or subunit thereof (claim 1), wherein the collagen post-translational enzyme is the an alpha subunit of prolyl-4-hydroxylase and a beta subunit of prolyl-4-hydroxylase (claims 5-6), wherein the collagen is human recombinant collagen (Abstract, [0003]). Kivirikko teaches another vector comprising a polynucleotide molecule having a nucleic acid sequence which encodes a second collagen subunit (claim 3).
Regarding claim 4, Kivirikko teaches that the vectors also encode a selectable marker, that encodes a product necessary for the host cell to grow [0109, 0113, 0118].
Regarding claim 10-11, Kivirikko teaches a system wherein the collagen post-translational enzyme is an alpha subunit of prolyl-4-hydroxylase and a beta subunit of prolyl-4-hydroxylase (claims 5-6), wherein the collagen is human recombinant collagen (Abstract, [0003, 0204], Table III).
Regarding claim 12, Kivirikko teaches that the mammalian host cells include, but are not limited to, CHO, VERO, BHK, HeLa, COS, MDCK, 293, WI38 [0112].
Regarding claim 13, Kivirikko teaches that the media is serum-free medium [0161, 0197].
Regarding claim 45, Kivirikko teaches that the mammalian host cells include, but are not limited to, CHO, VERO, BHK, HeLa, COS, MDCK, 293, WI38 [0112].
Claims 5, and 46-49 are rejected under 35 U.S.C. 103 as being unpatentable over Kivirikko et al . (US20020142391A1 – hereinafter “Kivirikko”) in view of Viswanathan et al. (US 2015/0011733A1 – herein after “Viswanathan”) as applied to claim 1 above, and further in view of Chou et al. (US20070087405A1 – hereinafter “Chou”) and Jin et al. (US20110178157A1 – hereinafter “Jin”).
The teachings of Kivirikko and Viswanathan are disclosed above and incorporated herein by reference.
Kivirikko does not teach sequence recited in claim 5 and 47.
Chou teaches an expression system for producing collagen comprising a recombinant insect cell comprising a transfected polynucleotide encoding prolyl 4-hydroxylase, consisting of SEQ ID NOs: 3 and 5; transfecting an expression vector comprising a recombinant collagen polynucleotide into the cell; culturing the cell under conditions such that the recombinant collagen polynucleotide is expressed; and recovering the expressed recombinant collagen (Title; Abstract; claim 1). Chou teaches use of serum free media [0053]. Chou teaches that the cell includes a transfected gene encoding prolyl 4-hydroxylase and that the gene includes α subunit and/or β subunit of prolyl 4-hydroxylase, that the α subunit of prolyl 4-hydroxylase includes the nucleotide sequence of SEQ ID NO: 3, and the β subunit of prolyl 4-hydroxylase includes the nucleotide sequence of SEQ ID NO: 5. Chou teaches that the cell further includes a transfected gene encodes a collagenous (COL1) domain [0023]. Examiner notes that SEQ ID NO: 3 and 5 are identical to the instant SEQ ID Nos. 28 and 30. Chou teaches that co-expression of collagen genes and cDNAs encoding the two subunits of prolyl 4-hydroxylase has led to the synthesis of completely hydroxylated, thermally stable collagens [0033].
Examiner notes that that Viswanathan teaches addition of HSP47 but does not disclose the sequence. However, such a sequence is known in the art as taught by Jin et al. Jin teaches methods and kits for modulating expression of target genes, particularly heat shock protein 47 (hsp47) and teaches the HSP47 sequence of SEQ ID NO: 1 (Abstract; [0009]), which reads on the instant HSP47 or functional variant of SEQ ID NO: 32.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Viswanathan and Chou and use the prolyl 4-hydroxylase with the nucleotide sequence of SEQ ID NO: 3 and 5 since Chou teaches co-expression of both collagen and prolyl 4-hydroxylase. It would have been obvious to modify Viswanathan and use the HSP47 sequence as taught by Jin since Jin teaches nucleotide sequences for expressing HSP47 (Abstract; [0009]). One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using the alpha and beta isoforms of prolyl 4-hydroxylase since Chou teaches that co-expression of collagen genes and cDNAs encoding the two subunits of prolyl 4-hydroxylase has led to the synthesis of completely hydroxylated, thermally stable collagens [0033].
Regarding claim 5, Kivirikko teaches that the system comprises polynucleotides expressing col7, and alpha and beta proly l4-hydroxylase but does not teach the sequences. Viswanathan teaches a method that comprises providing a cell, e.g., a mammalian cell, e.g., a CHO or HEK cell, genetically modified to express collagen 7, or a functional fragment thereof, and, optionally, one or more polypeptides, e.g., one or more polypeptides that increase collagen 7 production in the cell such as prolyl hydroxylase, culturing the cell under conditions sufficient for the production of collagen 7, or functional fragment thereof, thereby making collagen 7, or a functional fragment thereof [0004-0006, 0034-0038]. Viswanathan teaches the polynucleotide sequence of human collagen 7 of SEQ ID NO: 1 [0062] which is identical to the instant SEQ ID NO: 25. Even though Viswanathan teaches including prolyl hydroxylase, Viswanathan does not teach the sequences of SEQ ID NO: 28 ad 30. However, Chou teaches that the cell includes a transfected gene encoding prolyl 4-hydroxylase and that the gene includes α subunit and/or β subunit of prolyl 4-hydroxylase, that the α subunit of prolyl 4-hydroxylase includes the nucleotide sequence of SEQ ID NO: 3, and the β subunit of prolyl 4-hydroxylase includes the nucleotide sequence of SEQ ID NO: 5. Chou teaches that the cell further includes a transfected gene encodes a collagenous (COL1) domain [0023]. Examiner notes that SEQ ID NO: 3 and 5 are identical to the instant SEQ ID Nos. 28 and 30. It would have been obvious to modify Kivirikko to include the sequences of Chou and Viswanathan.
Regarding claims 47-49, Viswanathan teaches vectors that include expressing HSP47 [0072], and that host cells are recombinantly manipulated to express the human HSP47 and that HSP47 assists in the translocation of procollagen into the endoplasmic reticulum and also helps maintain the emerging polypeptide in an unfolded state until synthesis is complete [[0068]. Further, Viswanathan already teaches using exogenous polynucleotides, and thus one of ordinary skill in the art would be motivated to use exogenous polynucleotide for expressing HSP47. With regards to the HSP47 sequence, Jin teaches methods and kits for modulating expression of target genes, particularly heat shock protein 47 (hsp47) and teaches the HSP47 sequence of SEQ ID NO: 1 (Abstract; [0009]), which reads on the instant HSP47 or functional variant of SEQ ID NO: 32. It would have been obvious to modify Kivirikko and use the HSP47 sequence as taught by Jin.
Response to Arguments
Applicant's arguments filed 09/08/2025 have been fully considered but they are not persuasive.
Applicant argues that independent claim 1 has been amended to recite that the production system comprises vectors comprising exogenous polynucleotide.
The arguments presented above have been fully considered but are unpersuasive. Examiner notes that all the steps (a-c) are taught by Kivirikko. Kivirikko generally teaches that the vector comprises polynucleotide but doesn’t explicitly teach exogenous polynucleotide. However, the use of exogenous polynucleotide is known in the art as taught by Viswanathan et al. Viswanathan teaches a method that comprises providing a cell, e.g., a mammalian cell, e.g., a CHO or HEK cell, genetically modified to express collagen 7, or a functional fragment thereof, and, optionally, one or more polypeptides, e.g., one or more polypeptides that increase collagen 7 production in the cell such as prolyl hydroxylase, culturing the cell under conditions sufficient for the production of collagen 7, or functional fragment thereof, thereby making collagen 7, or a functional fragment thereof [0004-0006, 0034-0038]. Viswanathan teaches that the cell comprises exogenously introduced nucleic acids that encode the collagen 7 and the prolyl hydroxylase (claims 4-6). One of ordinary skill in the art would be motivated to use exogenously introduced polynucleotides to optimize production of the recombinant collagen 7. The arguments are unpersuasive.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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