DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on 1-16-2026 has been entered.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1 and 4-26 are pending and under examination. The allowability of the claims is withdrawn in view of the art rejections set forth below.
Priority
The present application claims benefit of two documents under 35 USC 119(a)-(d), China 202010188038.1 and PCT/CN2020/109645. The '038.1 document is not in English and therefore the examiner cannot determine whether it discloses the now-claimed invention. However the '645 document discloses the now-claimed invention; see for example Figure 1. The present application also claims domestic benefit of U.S. application 16/877069, now U.S. Patent 11207349. That application discloses the now-claimed invention; see for example original claims 1, 3, and 6. Therefore for the purposes of applying prior art, the effective filing date of the present claims is 18 May 2020, the date that '069 was filed.
Information Disclosure Statement
The information disclosure statement filed 1-16-2026 has been considered. An intialed copy is enclosed.
Claim Rejections - 35 USC § 102
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)(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.
Claims 1-11 and 13-26 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Chen et al (US 12,053,491 with priority to at least December 14, 2015).
Chen et al claims a bispecific chimeric antigen receptor as set forth below:
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The ofatumumab antibody comprises the CDRs and SEQ ID NOS: 4 and 3 as set forth in the instant claims.
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A comparison of SEQ ID NO:4 with the light chain sequence of Ofatumumab known to the prior art.
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A comparison of SEQ ID NO:3 with the heavy chain sequence of Ofatumumab of the prior art. A copy of the Ofatumumab heavy and light chain sequences were obtained from:gsrs.ncats.nih.gov/ginas/app/ui/substances/M95KG522R0 for the comparisons set forth supra. Thus, the Ofatumumab as cited in the claims, necessarily comprise the CD20 binding sequences set forth in instant claims 1 and claims dependent thereon.
The instantly claimed anti-CD19 antibody variable heavy chain regions and variable light chain regions are also identical to the heavy and light chain variable regions of the anti-CD18 scFV as set forth in SEQ ID NO:4 of Chen et al. Instant SEQ ID NO:5 (VH2) aligned with SEQ ID NO:4.
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Instant SEQ ID NO:6 aligned with SEQ ID NO:4 of Chen et al
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Chen et al also teaches the specific N to C terminal order of the light and heavy variable regions as claimed in 1, 4, 5, 6 and associated nucleic acids, vectors, immune host cells (see claims 1-9 of Chen et al). Chen et al also teaches that the bispecific chimeric antigen receptor comprises a spacer of SEQ ID NO:5 which is an IgG4 hinge, a transmembrane domain (CD28; SEQA IDN O:6), a co-stimulatory domains (CD28 and 4-1BB) and a CD3-zeta cytoplasmic signaling domain (see columns 12-13). Chen et al also teach the presence of a signal peptide sequence (see Figure 1) from GM-CSF (column 13, lines 5-7). Chen et al teach a CAR where the spacer between the anti CD20 and anti-CD19 antibodies is (G4S)1 as in the instant SEQ ID NO:16 (see column 3, lines 12-25). As such, Chen et al teach and claim at least one of the elements from each of claims 7-11 anticipating the instant invention. As to claims 13-17, Chen et also claim immune cells comprising the polypeptide, nucleic acid encoding the polypeptide and vectors comprising the nucleic acids (see claims 5-9). As to claims 17-21 and 23-26, Chen et al teach using the cells for treating/killing cancer cells where the individual may have a B-cell malignancy expressing one or both of CD20 and CD19 (column 2, lines 60-66). Cancers that may be treated are B-cell lymphomas and leukemias, Hodgkin’s disease, non-Hodgkin’s lymphoma, hairy cell leukemia, CLL and myeloma (see column 7 and column 9, lines 40-50). The instantly claimed functional properties of the bispecific CAR of claims 23-26 are linked to the structure of the chimeric receptor present and as such, the functional properties are necessarily present. As to claim 22, Chen et al teach that the cells can be autologous cells, syngeneic cells or allogeneic cells (see column 9, lines 30-32).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 8, 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (US 12,053,491 with priority to at least December 14, 2015) in view of Orentas et al (US 2024/0034802, with priority to July 31, 2018).
The teachings of Chen et al are set forth supra. Chen et al differs by not reciting alternates for the co-stimulatory region(s), the hinge region(s) and the transmembrane domain(s) as set forth in instant claims 8, 10 and 11.
Orentas et al teach a tandem bispecific chimeric antigen receptor (see Figure 1 B) where the hinge and transmembrane are derived from CD8, the costimulatory region is from 4-1BB (aka CD137) and the cytoplasmic signaling domain is CD3zeta. Orentas et al teach functional alternatives for the linker domain (instant claim 10 hinge region) are derived from the extracellular domain of CD8 or CD28 (see paragraph [0029]) as they are linked to the transmembrane region. As to instant claim 11, alternates for the transmembrane domain are: CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD83, CD86, CD134, CD137, CD154 and combinations thereof (paragraph [0030]). Orentas et al teach the CAR comprises at least one costimulatory domain of OX4, CD70, CD27, CD28, CD5, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), DAP10, DAP12, 4-1BB(CD137) or combinations thereof (see paragraph [0034]) as it relates to instant claim 8.
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to substitute or add one or the functionally equivalent domains of Orentas et al to or for the same domains of Chen et al in the bispecific CAR of Chen et al because Orentas et al teach that the domains can be used as alternates or in combination in for the disclosed CD20/19 bispecific CAR and other bispecific CARs.
Free of the Prior Art
Claim 12 as drawn to the bispecific CAR compising the amino acid seqeunce set forth in SEQ ID NO:16 is free of the prior art.
Claim 12 is 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
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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/Patricia Duffy/Primary Examiner, Art Unit 1645