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 .
This office action is in response to an amendment filed 12/9/2025.
Claims 1, 5, 9, 10, 17, 18, 20, 21, 23, 27, 28, 30-35 and 37-47 are pending.
This application is a filing of PCT/EP20-021 filed 6/17/2021 which claims priority to U.S. Provisional Patent Application Serial No. 63/040,101 filed on June 17, 2020 and U.S. Provisional Patent Application Serial No. 63/058,783 filed on July 30, 2020.
Information Disclosure Statement
An information disclosure statement filed 12/9/2025 has been identified and the documents considered. The corresponding signed and initialed PTO Form 1449 has been mailed with this action.
Response to Amendments
Applicants’ amendments are sufficient to overcome the previous objections, rejections under 35 USC 112, second and first.
As to the rejection under prior art, the previous rejections have bene overcome. However, new art necessitated by amendment has been identified.
Claim Objections
Claims 18, 28 and 42 objected to because of the following informalities: Upon reconsideration, claim 18 should be amended to be consistent with claim 17 from which it depends to recite –the one or more co-stimulatory agents--. This is true of claim 42 which depends similarly to claim 41. This is a new observation. Appropriate correction is required.
Claim 34 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 32. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Upon a closer reading of the disclosure, it appears that the step of administering the bispecific antibody is responsible for the lymphodepletion and/or immunosuppression and hence there are no additional steps to claim 34 and it is a duplicate of claim 32. This is a new observation.
Claim Rejections - 35 USC § 112, second paragraph
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.
Claims 10, 28, 37 and 38 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. These are new rejections necessitated by applicants’ amendment.
Claim 10 recites the limitation "the cell therapy" in claim 9. There is insufficient antecedent basis for this limitation in the claim as this phrase is removed from claim 9.
Claims 28, 37 and 38 recite the limitation “the anti-CD3 antibody” in reference to the bispecific antibody that binds to CD3 and IL-6R. There is insufficient antecedent basis for this limitation in the claim. The claims were previously drawn to anti-CD3 antibodies but has been amended to recite a bispecific antibody wherein referring to just the anti-CD3 antibody is improper. For example, in claims 37 and 38, the dose is only measured in terms of the anti-CD3 antibody but there is a bispecific antibody so the dose needed is unclear. A bispecific antibody is only partially referenced by referring to the anti-CD3 antibody.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tan et al (U.S. 20150232557).
Tan et al teach methods of creating bispecific antibodies ¶0193. The bispecific binding domains are to CD3 and IL-6R.
At least the CD3 component leads to induced activation and expansion as required of claim 1. This component also called OKT3 induced proliferation in vitro for in vivo use (see ¶0005). This refers to ex vivo manipulation as recited in claim 1. IL-6R is used in conjunction with the CD3 antibody.
Claim Rejections - 35 USC § 103
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 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.
Claims 1, 5, 9 and 10 are rejected as obvious over Priyadharshini et al (Transplant Rev (Orlando). 2012, 212–222) in view of Mizuno et al (US 20220153875).
Priyadharshini et al teach that activation of T cells functions to improve graft survival (see abstract).
To this end, Mizuno et al teach that the use of a bispecific antibody with binding to IL-6R and CD3 results in T cell activation (see ¶1288).
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to enhance T cell activation by the method provided for by Priyadharshini et al. As noted above: 1) Priyadharshini et al teach that T cell activation correlates with allograft survival; 2) Mizuno et al teach means to trigger enhanced t cell activation. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the expanded method would allow improved treatment.
The antibody can be combined with a CAR T cell which is itself activated (see Mizuno et al, ¶1311).
Claims 1, 5, 9, 10, 27, 28, 30, 31, 39, 40, 46 and 47 are rejected as obvious over Tan et al (U.S. 20150232557) in view of Hsiu et al (US 11,807,662) and Ferlin et al (U.S. Patent 8,034,344).
As to the sequences claimed, they were known in the art and available to a practitioner. For example, Hsiu et al teach the sequences as part of anti-CD3 as shown below. The sequences below are SEQ ID NO:48 and 49 which comprise all of SEQ ID NO:s 42-47.
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Ferlin teaches anti-IL-6R in Table 1 (VH) and (VL) 2,
VH CDR1 corresponding to SEQ ID NO:15 SYAIS
CDR2 corresponding to SEQ ID NO:37- GIIPLFDTTKYAQQFQG CAR
CDR3 corresponding to SEQ ID NO:35 DRDILTDYYPMGGMDV
VL CDR1 corresponding to SEQ ID NO:24- RASQGISSVLA
CDR2 corresponding to SEQ ID NO:25 DASSLES
CDR3 corresponding to SEQ ID NO:26 QQSNSYPLT
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to incorporate sequences provided in the art for methods using compounds having those sequences. Hsiu and teaches the sequences for anti-CD3. Ferline for anti-IL6R. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that known sequences could be used in known uses for those molecules.
Conclusion
Claims 17-18,20-21,23,32-35, 37, 38 and 41-45 are free of the art however, not all claism are free of rejection.
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 MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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/MARIA MARVICH/Primary Examiner, Art Unit 1634