DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of Group I, presently claims 1-4, 9, 12, 13, 16-19, and 23-30 in the reply filed on 7/22/2026 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)).
Claim 33 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/22/2026.
Claims 1-4, 9, 12, 13, 16-19, and 23-30 are under consideration on the merits.
Claim Objections
Claim 33 is objected to as being non-compliant under 37 C.F.R. § 1.121(c). Claim 33 is withdrawn from consideration, but the claim was not amended with the instant reply to reflect this updated status. Correction is required with Applicant’s next reply.
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 17 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.
Claim 17 recites “a human therapeutic or prophylactic agent.”, which blurs the metes and bounds of this claim because it is unclear if “human” in this context is a limitation to 1) generic agent further capable of treating or prophylactically treating a human subject, or 2) a generic agent obtained from a human. These interpretations are mutually exclusive, and so clarification and/or correction is required. While the specification at page 2 appears to contemplate the narrower embodiment of monoclonal antibodies, the examiner is precluded from importing limitations from the specification into the claims to otherwise clarify indefinite claim language; see M.P.E.P. § 2111.01(II).
Claim Rejections - 35 USC § 103
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.
Claims 1-4, 9, 12, 13, 16-19, and 23-29 are rejected under 35 U.S.C. 103 as being unpatentable over Keck et al.(WO 2020/041174; provided in the IDS 1/14/2025).
Keck teaches immunodeficient mouse strains derived from NSG mice and expressing transgenes encoding for encoding for human interleukin-3, human granulocyte/macrophage-colony stimulating factor 2, and human stem cell factor (page 11, the paragraph starting “Various immunodeficient…” through the paragraph spanning pages 11-12, i.e. the “NSG-SGM3” mouse), reading in-part on claim 1. Keck teaches another embodiment of an immunodeficient mouse strain derived from NSG mice and expressing a transgene for human interleukin-15 (page 11, the paragraph starting “Various immunodeficient…”), reading in-part on claim 1. Keck teaches administering human PMBCs to the NSG-SGM3 transgenic mice (Example 20 on pages 63-64), reading in-part on claim 1. Keck teaches myeloablative treatment comprising treatment with 100 cGy of x-ray radiation (Example 20 on page 64), reading on claims 2-4. Keck teaches administering a dosage less than 1x107 human PBMCs (page 10, the paragraph referencing Fig. 26; i.e. 3.0x106 human PBMCs), reading on claim 9. Keck teaches administering the human PBMCs within 4 hours of irradiation (Example 1), reading on claims 12 and 13. Keck teaches a subset of the human PBMCs were obtained from donors categorized as having a severe/high cytokine response and likely to develop cytokine release syndrome as measured by the human cytokine release (e.g. human IFN-y, IL-2, IL-4, IL-6, IL-10, and TNF) from the transgenic murine subjects (i.e. CRS; Fig. 5 and 6 and Example 6 on pages 51-54), reading on the embodiment of CRS for the human diseased cells of claim 16 and reading on claims 27 and 28. Keck teaches administering pembrolizumab (e.g. a species of humanized monoclonal antibody; KEYTRUDA®) 6 days after human PBMC engraftment (Example 15 at pages 59-61 and Fig. 18), reading on that embodiment of claims 17-19 and 23-26. Keck teaches obtaining human PBMCs from engrafted the immunodeficient transgenic mice and staining the human blood cells with human antibodies (e.g. immunoglobins) and then detecting cell marker expression by flow cytometry (Example 16 at pages 61-62 and Fig. 19), reading on claim 29
Regarding claim 1, it would be prima facie obvious to combine different components (i.e. transgenes encoding for cytokines) taught as useful for the same purpose into a single transgenic and immunodeficient mouse. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) and M.P.E.P. § 2144.06. In this case, Keck teaches two different immunodeficient mouse strains derived from NSG mice with one strain expressing transgenes encoding for human interleukin-3, human granulocyte/macrophage-colony stimulating factor 2, and human stem cell factor (i.e. the NSG-SGM3 mouse) and a second strain expressing a transgene for human interleukin-15. Therefore, their combination must be held prima facie obvious absent any persuasive showing of nonobviousness to the contrary.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Keck as applied to claims 1 and 29 above, and further in view of Partridge et al. (Journal of Immunological Research (2016), Article ID 6262383, 6 pages; Reference U).
The teachings of Keck are relied upon as set forth above.
Regarding claim 30, Keck does not teach detecting one or more human IgG immunoglobins.
Patridge teaches that biotherapeutics often elicit unwanted immune response that produces non-neutralizing and/or neutralizing anti-drug antibodies (ADAs) and which comprising IgG, IgM, and IgA antibody isotypes (the first paragraph under the 1st page). Partridge teaches that generic ADA ELISA assays are capable of measuring IgG immunoglobulin ADA in mammals by utilizing anti-human constant region antibodies to capture the drug (of interest) and anti-mouse or anti-cynomolgus IgG species-specific antibodies to detect the drug-ADA complex (the paragraph spanning pages 3-4), reading in claim 30.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to add the generic ADA ELISA assays of Patridge to the methods of Keck. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Keck teaches detailed methods of treating humanized mice with antibody biotherapeutics, and because Partridge teaches that generic ADA ELISA assays are capable of measuring IgG immunoglobulin ADA in mammals treated with human biotherapeutics. The skilled artisan would have been motivated to do so because Partridge teaches that biotherapeutics often elicit unwanted immune response that produces non-neutralizing and/or neutralizing anti-drug antibodies (ADAs) and which comprising IgG, IgM, and IgA antibody isotypes, and so the addition would predictably improve upon the methods of Keck by further assaying for anti-drug antibodies in Keck’s humanized mouse subjects.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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