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. Applicant’s amendment to the claims filed on 08/04/2026 in response to the Non-Final Rejection mailed on 05/04/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 1-23 are pending.
4. Claim 23 stands withdrawn pursuant to 37 CFR 1.142(b).
5. Applicant’s remarks filed on 08/04/2026 in response to the Non-Final Rejection mailed on 05/04/2026 have been fully considered and are deemed not persuasive to overcome the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Information Disclosure Statement
6. The IDSs filed on 07/14/2026 and 08/04/2026 have been considered by the examiner and copies of the Form PTO/SB/08 are attached to the office action.
Claim Rejections - 35 USC § 112(b)
7. The rejection of claim 4 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for lack of antecedent basis is withdrawn in view of applicants’ amendment to the claims.
8. The rejection of claims 6 and 19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the relative term “about” is withdrawn in view of applicants’ amendment to the claims to remove the recited term.
9. The rejection of claims 1-22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the recitation of “mutations numbered according to the EU system and selected from the group consisting of: L242C, A287C, R292C, N297G, V302C, L306C, and K334C” and “comprises the mutations N297G and at least one of R292C and V302C” is maintained for the reasons of record and the reasons set forth below. The recitation of “mutations numbered according to the EU system and selected from the group consisting of: L242C, A287C, R292C, N297G, V302C, L306C, and K334C” and “comprises the mutations N297G and at least one of R292C and V302C” is indefinite because it is unclear which sequence of therapeutic protein the claim is referring to. Without a sequence to compare, it is unclear based on the numbering system which amino acids have the claimed substitutions. Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from the claims. It is suggested that applicants clarify the meaning of the claims.
RESPONSE TO REMARKS: Beginning on p. 5 of applicants’ remarks, applicants in summary contend that the comparative sequence is wild type IgG1 and EU index is a standardized numbering system keyed to the wild type human IgG1 constant region sequence.
This argument is found to be not persuasive because the claim does not specify which species of IgG1 constant region is being claimed, and it is known that despite the region being named “constant region”, this region can vary sequentially between species. As such, as stated above, without a sequence to compare, it is unclear based on the numbering system which amino acids have the claimed substitutions.
Claim Rejections - 35 USC § 103
10. The rejection of claims 1-7, 9-13, 16-17, and 20-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ali et al. (WO 2019/028316 A1; cited on IDS filed on 02/05/2024) in view of Hermans et al. (WO 2012/105833 A1; cited on IDS filed on 02/05/2024) is maintained for the reasons of record and the reasons set forth below.
11. With respect to claim 1, Ali et al. teach methods of isolating a therapeutic protein comprising a IgG1 constant region comprising one or more of the following mutations numbered according to the EU system and selected from the group consisting of: L242C, A287C, R292C, N297G, V302C, L306C, and K334C and eluting the therapeutic protein [see Abstract; paragraphs 00180-00182; 00304].
With respect to claim 3, Ali et al. teach the method wherein the sample comprises serum [see paragraph 00302].
With respect to claim 4, Ali et al. teach the method wherein the sample comprises albumin bound to the therapeutic protein [see paragraph 00280].
With respect to claim 9, Ali et al. teach the method wherein the therapeutic protein is an antigen binding protein and is bound to its antigen in the sample and wherein the therapeutic protein remains bound to its antigen after eluting [see paragraphs 00180-00182].
With respect to claim 10, Ali et al. teach the method further comprising applying at least one analytical technique to the therapeutic protein [see paragraphs 00305-00312].
With respect to claim 13, Ali et al. teach the method wherein the therapeutic protein is an antigen binding protein and is bound to its antigen in the sample and wherein the therapeutic protein remains bound to its antigen after eluting [see paragraphs 00180-00182].
With respect to claim 16, Ali et al. teach the method wherein the therapeutic protein comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 2 [see alignment attached as APPENDIX A].
With respect to claim 20, Ali et al. teach wherein the IgG1 constant region of the therapeutic protein comprises the mutations N297G and at least one of R292C and V302C [see paragraphs 00180-00182].
With respect to claim 21, Ali et al. teach the method wherein the therapeutic protein comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 2 [see alignment attached as APPENDIX A].
With respect to claim 22, Ali et al. teach the method wherein the therapeutic protein is a monoclonal antibody or a recombinant protein [see Abstract; paragraphs 00150-00157].
However, Ali et al. does not teach the method of claim 1 of incubating the sample comprising the therapeutic protein with an antibody immobilized on a substrate, wherein the antibody binds selectively, compared to wild type IgG1, to said IgG1 constant region comprising one or more mutations, whereby the immobilized antibody binds to the IgG1 constant region of the therapeutic protein; the method of claim 2, wherein the sample is an ex vivo sample of a human; the method of claim 5, wherein the ex vivo sample comprises immunoglobulins, wherein said immunoglobulins are different from the therapeutic protein; the method of claim 6, wherein the incubating is for about 15 minutes or less; the method of claim 7, wherein the eluting is at pH 3-3.5; the method of claim 11, further comprising applying the eluted therapeutic protein to a chromatography column; the method of claim 12, wherein the chromatography is size exclusion chromatography; the method of claim 13, wherein the size exclusion chromatography comprises detecting a complex of the therapeutic protein bound to its antigen; and the method of claim 17, wherein the antibody is a mouse monoclonal antibody.
Hermans et al. teach methods for the purification of human IgG constant regions comprising an antigen binding protein that is capable of binding to the constant region of human IgG wherein the antigen binding protein is a monoclonal antibody that is immobilized to a substrate, washing the immobilized antibody bound to the constant region and eluting the therapeutic protein that permits the capture and purification of all human or humanized IgG and fragments thereof [see Abstract; p. 4-5].
With respect to claim 2, Hermans et al. teach the method wherein the sample is a human plasma derived feed stock samples [see p. 12, top].
With respect to claim 5, Hermans et al. teach the method wherein the ex vivo sample comprises immunoglobulins that are different from the therapeutic protein [see p. 12, top].
With respect to claim 7, Hermans et al. teach the method wherein the eluting is at pH about 3 (overlaps the claimed range) [see p. 11, top].
With respect to claims 11-13, Hermans et al. teach the method of applying the eluted therapeutic protein to a size exclusion chromatography column [see Example 9].
With respect to claims 16-17, Hermans et al. teach the method wherein the antibody is a monoclonal antibody raised against the protein and can be a mouse monoclonal antibody [see p. 3-5].
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 Ali et al. and Hermans et al. according to the teachings of Hermans et al. because Ali et al. teach methods for generating and isolating therapeutic proteins comprising a mutated IgG1 constant region. Hermans et al. teach methods for the purification of human IgG constant regions comprising an antigen binding protein that is capable of binding to the constant region of human IgG wherein the antigen binding protein is a monoclonal antibody that is immobilized to a substrate, washing the immobilized antibody bound to the constant region and eluting the therapeutic protein that permits the capture and purification of all human or humanized IgG and fragments thereof. One of ordinary skill in the art desiring to purify a specific therapeutic protein comprising an IgG constant region would have a reasonable expectation of success, a reasonable level of predictability to combine the teachings of Ali et al. and Hermans et al. because Hermans et al. acknowledges their method permits the purification of all human or humanized IgG in a few steps which in turn would reduce overall costs in production of therapeutic proteins. 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.
Although the combination of Ali et al. and Hermans et al. does not explicitly teach an incubation time of about 15 minutes or less, this modification would have been obvious to one of ordinary skill in the art because MPEP 2144.05.II.A 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, one of ordinary skill in the art would desire to optimize the incubation time in order to maximize bound protein to isolate as much protein as possible.
12. The rejection of claim 14 under 35 U.S.C. 103 as being unpatentable over Ali et al. (WO 2019/028316 A1; cited on IDS filed on 02/05/2024) in view of Hermans et al. (WO 2012/105833 A1; cited on IDS filed on 02/05/2024) as applied to claims 1-7, 9-13, 16-17, and 20-22 above, and further in view of Anderson et al. (Journal of Proteome Research, 2004; cited on PTO-892 mailed on 05/04/2026) is maintained for the reasons of record and the reasons set forth below.
13. The relevant teachings of Ali et al. and Hermans et al. as applied to claims 1-7, 9-13, 16-17 and 20-22 are set forth above.
However, the combination of Ali et al. and Hermans et al. do not teach the method of claim 14, further comprising performing mass spectrometry on the isolated antibody.
Anderson et al. teach that mass spectrometry techniques such as LC-MS/MS provide sufficient separation and quantitative analysis of thousands of peptides in serum digests which permit the ability to quantitate and detect many proteins at once [see Abstract; p. 235].
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 Ali et al., Hermans et al. and Anderson et al. to include mass spectrometry in the methods of Ali et al. and Hermans et al. because Anderson et al. teach that mass spectrometry techniques such as LC-MS/MS provide sufficient separation and quantitative analysis of thousands of peptides in serum digests which permit the ability to quantitate and detect many proteins at once. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability and would be motivated to use mass spectrometry in order to quantitate the effectiveness of the purification of the therapeutic protein desired in order to validate the method. 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.
14. The rejection of claims 18-19 under 35 U.S.C. 103 as being unpatentable over Ali et al. (WO 2019/028316 A1; cited on IDS filed on 02/05/2024) in view of Hermans et al. (WO 2012/105833 A1; cited on IDS filed on 02/05/2024) as applied to claims 1-7, 9-13, 16-17, and 20-22 above, and further in view of Liu et al. (Journal of Applied Polymer Science, 2004; cited on PTO-892 mailed on 05/04/2026) is maintained for the reasons of record and the reasons set forth below.
15. The relevant teachings of Ali et al. and Hermans et al. as applied to claims 1-7, 9-13, 16-17 and 20-22 are set forth above.
With respect to claims 18-19, Hermans et al. teach methods for the purification of human IgG constant regions comprising an antigen binding protein that is capable of binding to the constant region of human IgG wherein the antigen binding protein is a monoclonal antibody that is immobilized to a substrate, washing the immobilized antibody bound to the constant region and eluting the therapeutic protein that permits the capture and purification of all human or humanized IgG and fragments thereof [see Abstract; p. 4-5].
However, the combination of Ali et al. and Hermans et al. does not teach the method of claim 18, wherein the substrate comprises a bead and the method of claim 19, wherein the bead comprises one or more non-porous monodisperse superparamagnetic beads wherein each bead has an average diameter of about 2-4 mM.
Liu et al. teach preparation of superparamagnetic immunomicrospheres in the size range of 1 to 5 mm that provide effective and efficient purification of antibodies [see Abstract; p. 2211, column 1].
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 Ali et al., Hermans et al. and Liu et al. to use superparamagnetic beads in the methods of Ali et al. and Hermans et al. because Ali et al. and Hermans et al. teach methods for the isolation of a therapeutic protein wherein the protein is antibody. Liu et al. teach superparamagnetic immunomicrospheres provide effective and efficient purification of antibodies. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability and would be motivated to combine the teachings of Ali et al., Hermans et al. and Liu et al. because Liu et al. acknowledges that superparamagnetic beads provide effective and efficient purification of antibodies. 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.
Response to Remarks Regarding Prior Art Rejections
16. Beginning on p. 16 of applicants’ remarks, applicants in summary contend that the combination of mutated therapeutic protein of Ali et al. with the generic all-IgG capture of Hermans’ does not yield and would not motivate a person of ordinary skill in the art to develop an antibody with selective binding to the mutated constant region to purify the mutated therapeutic protein because such an antibody would defeat the purpose of Hermans et al.
This argument is found to be not persuasive because the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). As stated in the rejection above, one of ordinary skill in the art desiring to purify a specific therapeutic protein comprising an IgG constant region would have a reasonable expectation of success, a reasonable level of predictability to combine the teachings of Ali et al. and Hermans et al. because Hermans et al. acknowledges their method permits the purification of all human or humanized IgG in a few steps which in turn would reduce overall costs in production of therapeutic proteins. Given that the art already recognizes the mutated IgG1 constant regions and their usefulness in fusion proteins for the isolation of pharmaceutical compositions as taught by Ali et al., it would require routine skill for one of ordinary skill in the antibody art to design a monoclonal antibody that is immobilized to a substrate to target the mutant constant region based on the methods of Hermans et al.
Conclusion
17. Status of the claims:
Claims 1-23 are pending.
Claim 23 stands withdrawn pursuant to 37 CFR 1.142(b).
Claims 1-22 are rejected.
No claims are in condition for an allowance.
THIS ACTION IS MADE FINAL. 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 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
Ali et al. with SEQ ID NO: 2
Query Match 100.0%; Score 1776; Length 335;
Best Local Similarity 100.0%;
Matches 330; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
Qy 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 120
Qy 121 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYG 180
Qy 181 STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 240
Qy 241 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 300
Qy 301 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 330
||||||||||||||||||||||||||||||
Db 301 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 330
Prosecution Insights