DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1-23 are pending.
Priority
3. Acknowledgement is made of this divisional application of U.S. Non-provisional Application No. 16/615419, filed on 11/21/2019, which is a national stage entry of PCT/EP2018/064102, filed on 05/29/2018 which claims foreign priority under 35 U.S.C. 119(a)-(d) to Great Britain Patent Application No. GB1708655.4, filing date 05/31/2017. The certified copy has been filed in the parent ‘419 application, filed on 11/21/2019.
Information Disclosure Statement
4. The IDSs filed on 08/23/2024 and 03/06/2025 have been considered by the examiner and a copies of the Form PTO/SB/08 are attached to the office action.
Drawings
5. The Drawings filed on 08/23/2024 and replacement drawings filed on 10/31/2024 are acknowledged and accepted by the examiner.
Claim Rejections - 35 USC § 102
6. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
7. Claim(s) 1, 5-7, 12, 15-16, and 18-22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Subramanian et al. (WO 2013/158275 A1; cited on IDS filed 08/23/2024).
8. Claims 1, 5-7, 12, 15-16, and 18-22 are drawn to a method for reducing the heterogeneity of the population of recombinant proteins in a batch produced in production phase by recombinant host cells comprising limiting the total amount of a) cysteine or cystine; and b) tryptophan present in the cell culture medium during the production phase of the recombinant protein.
9. With respect to claim 1, Subramanian et al. teach a method for producing a recombinant protein comprising culturing CHO cells transfected with a vector encoding the recombinant protein in a chemically defined media (medium free of animal derived products), supplementing the culture during a production phase with amino acids such as cysteine and tryptophan to control the amount of acidic species expressed by host cells [see Abstract; p. 1-2; Table 6; p. 83-84; p. 89, lines 19-26]. Subramanian et al. teach the process wherein the process reduces the heterogeneity of the recombinant protein produced by reducing charge heterogeneity [see p. 2, lines 7-13; p. 91, bottom].
With respect to claim 5, Subramanian et al. teach the method wherein the total amount of cysteine and tryptophan in the culture is reached by adding cysteine and tryptophan to the cell culture medium through the use of continuous or perfusion technology or by employment of an intermittent harvest strategy or through use of cell retention device technology [see p. 4, lines 9-19].
With respect to claim 6, Subramanian et al. teach the method wherein the process is a fed batch process [see p. 37, bottom].
With respect to claim 7, Subramanian et al. teach the process wherein the amino acids such as cysteine and tryptophan are provided through daily addition [see p. 37, bottom; p. 42, bottom].
With respect to claim 12, Subramanian et al. teach the method wherein the production is over the course of more than 10 days in the working examples [see p. 63; p. 77, lines 18-19].
With respect to claim 15, Subramanian et al. teach the method wherein the host cells are CHO cells (mammalian cells) [see Abstract; p. 1-2; Table 6; p. 83-84; p. 89, lines 19-26].
With respect to claim 16, Subramanian et al. teach the method wherein the recombinant protein is an antibody and is purified from the cell culture medium [see p. 2, lines 20-22; p. 23, lines 18-32].
With respect to claim 18, Subramanian et al. teach the method wherein the production phase is carried out in a bioreactor that is equal or more than 50 L [see p. 41, top; p. 96, top].
With respect to claim 19, Subramanian et al. teach the method wherein the recombinant protein is an antibody and is purified from the cell culture medium [see p. 2, lines 20-22; p. 23, lines 18-32].
With respect to claim 20, Subramanian et al. teach the method wherein the purification comprises Protein A chromatography [see p. 44, lines 3-20].
With respect to claim 21, Subramanian et al. teach the method further comprising a step of formulating the purified recombinant protein [see p. 5, top].
With respect to claim 22, Subramanian et al. teach the method wherein the method reduces the heterogeneity of the recombinant protein produced by reducing charge heterogeneity [see p. 2, lines 7-13; p. 91, bottom].
Claim Rejections - 35 USC § 103
10. 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.
11. Claim(s) 8 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Subramanian et al. (WO 2013/158275 A1; cited on IDS filed 08/23/2024).
12. The relevant teachings of Subramanian et al. as applied to claims 1, 5-7, 12, 15-16, and 18-22 are set forth in the 102(a)(1) rejection above.
With respect to claims 8 and 9, Subramanian et al. teach a method for producing a recombinant protein comprising culturing CHO cells transfected with a vector encoding the recombinant protein in a chemically defined media (medium free of animal derived products), supplementing the culture during a production phase with amino acids such as cysteine and tryptophan to control the amount of acidic species expressed by host cells [see Abstract; p. 1-2; Table 6; p. 83-84; p. 89, lines 19-26].
Although Subramanian et al. does not explicitly teach wherein cysteine or cystine and tryptophan is depleted in the culture before cysteine or cystine and tryptophan is added on the next day, MPEP 2144.05.I states “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”. In the instant case, it is routine for one of ordinary skill in the art to to determine from those experiments parameters, concentrations, and dosages of supplements to add to the culture media with the teachings of Subramanian et al. in hand to maximize the production of the antibody and efficacy of the product obtained. Such experimentation is routine for one of ordinary skill in the antibody production art. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
13. Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Subramanian et al. (WO 2013/158275 A1; cited on IDS filed 08/23/2024) in view of Bassett et al. (WO 2013/171156 A1; cited on IDS filed 08/23/2024).
14. The relevant teachings of Subramanian et al. as applied to claims 1, 5-7, 12, 15-16, and 18-22 are set forth in the 102(a)(1) rejection above.
With respect to claim 17, Subramanian et al. teach the method wherein the recombinant protein is an antibody and is purified from the cell culture medium [see p. 2, lines 20-22; p. 23, lines 18-32].
However, Subramanian et al. does not teach the method of claim 17, wherein the antibody or antigen binding fragment thereof comprises the antibodies of claim 17.
Bassett et al. teach antibody compositions recombinantly expressed in host cells that are useful in methods for treating diseases and disorders that comprise amino acid sequences that are 100% identical to the amino acid sequences of SEQ ID NOs: 1-6 [see Abstract; p. 28; alignment attached as APPENDIX A].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Subramanian et al. and Basset et al. to express the recombinant antibody of Basset et al. using the culture methods of Subramanian et al. because Subramanian et al. teach culturing methods using CHO cells comprising cysteine and tryptophan that reduce heterogeneity and guarantee antibody efficacy for pharmaceutical purposes. Basset et al. teach antibodies that are useful in methods of treating diseases and disorders. One of ordinary skill in the art would have a reasonable expectation of success, a reasonable level of predictability and would be motivated to combine the teachings of Subramanian et al. and Basset et al. because Subramanian et al. acknowledge culturing methods using CHO cells comprising cysteine and tryptophan that reduce heterogeneity and guarantee antibody efficacy for pharmaceutical purposes, and Basset et al. acknowledge antibodies that are useful in methods of treating diseases and disorders. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
15. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
16. Claim 22 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,077,796. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-20 of the ’796 patent recite a process for producing a recombinant protein comprising: a) culturing host cells capable of producing a recombinant protein in a medium free of animal-derived products wherein the host cells are CHO cells; b) supplementing the culture during production phase with cysteine or cystine in a total amount of from wt %12 to 28% wt of the expected total amount of recombinant produced; and tryptophan in a total amount of from 8 wt% to 30 wt% of the expected total amount of recombinant protein produced, c) an optionally recovering the recombinant protein from the cell culture medium wherein the recombinant protein is an antibody or an antigen-binding fragment thereof, wherein the recombinant protein is produced by the cells during said production phase, and wherein one or more initial experiments are performed to determine the expected total amount of recombinant protein produced.
Allowable Subject Matter
17. Claims 2-4, 10-11, and 13-14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
18. Status of the claims:
Claims 1-23 are pending.
Claims 1, 5-9, 12, and 15-22 are rejected.
Claims 2-4, 10-11 and 13-14 are objected to.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
APPENDIX A
Bassett et al. with SEQ ID NO: 1
Query Match 100.0%; Score 55; DB 20; Length 10;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GFTFSNYGMV 10
||||||||||
Db 1 GFTFSNYGMV 10
Bassett et al. with SEQ ID NO: 2
Query Match 100.0%; Score 94; DB 20; Length 17;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 YIDSDGDNTYYRDSVKG 17
|||||||||||||||||
Db 1 YIDSDGDNTYYRDSVKG 17
Bassett et al. with SEQ ID NO: 3
Query Match 100.0%; Score 43; DB 20; Length 8;
Best Local Similarity 100.0%;
Matches 8; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GIVRPFLY 8
||||||||
Db 1 GIVRPFLY 8
Bassett et al. with SEQ ID NO: 4
Query Match 100.0%; Score 78; DB 20; Length 16;
Best Local Similarity 100.0%;
Matches 16; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KSSQSLVGASGKTYLY 16
||||||||||||||||
Db 1 KSSQSLVGASGKTYLY 16
Bassett et al. with SEQ ID NO: 5
Query Match 100.0%; Score 31; DB 20; Length 7;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LVSTLDS 7
|||||||
Db 1 LVSTLDS 7
Bassett et al. with SEQ ID NO: 6
Query Match 100.0%; Score 54; DB 20; Length 9;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LQGTHFPHT 9
|||||||||
Db 1 LQGTHFPHT 9
