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.
Election/Restrictions
3. Applicant's election with traverse of Group I, claims 1-22 in the reply filed on 04/13/2026 is acknowledged. The traversal is on the ground(s) that Ali et al. does not each or suggest an antibody that binds selectively, compared to a wild-type IgG1, to an IgG1 constant region comprising the recited mutations. This is not found persuasive in view of the rejections of record set forth below.
The requirement is still deemed proper and is therefore made FINAL.
4. Claim 23 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04/13/2026.
Claims 1-22 are pending and examined on the merits.
Priority
5. Acknowledgement is made of applicants’ claimed domestic priority to U.S. Provisional Application No. 63/230483, filed on 08/06/2021.
Information Disclosure Statement
6. The IDS filed on 02/05/2024 has been considered by the examiner and a copy of the Form PTO/SB/08 is attached to the office action.
Drawings
7. The Drawings filed on 02/05/2024 are acknowledged and accepted by the examiner.
Claim Rejections - 35 USC § 112(b)
8. 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.
9. Claims 1-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1 (claims 2-19 and 21-22 dependent therefrom) and 20, 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.
Regarding claim 4, there is insufficient antecedent basis for the limitation “the ex vivo sample”.
Regarding claims 6 and 19, the term "about" is a relative term which renders the claim indefinite. The term "about" is a term of degree and the examiner has reviewed the specification and can find no examples or teachings that can be used for ascertaining the variance intended by the recited term of degree. Moreover, there is nothing in the specification or prior art of record to indicate that one of ordinary skill in the art could have ascertain the scope of the recited degree. It is suggested that applicant clarify the meaning of the claims. See Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. §112 and for Treatment of Related Issues in Patent Applications, 76 FR 7162 (Feb. 9, 2011), page 7165.
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) 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).
12. Claims 1-7, 9-13, 16-17 and 20-22 are drawn to a method of isolating a therapeutic protein from a sample, said therapeutic protein comprising an 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, the method comprising: 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 the one or more mutations, whereby the immobilized antibody binds to the IgG1 constant of the therapeutic protein; washing the immobilized antibody bound to the IgG1 constant region of the therapeutic protein; and eluting the therapeutic protein, thereby isolating the therapeutic protein.
13. 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.
14. Claim 14 is 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) 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; examiner cited).
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.
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.
16. Claims 18-19 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) 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; examiner cited).
17. 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.
Conclusion
18. 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.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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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