DETAILED ACTION
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 .
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 final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05 September 2025 has been entered.
Claim Status
Claims 1-13 and 15 are cancelled. Claims 14 and 16-33 as filed on 05 September 2025 are pending. Claims 25-29 are withdrawn. Claims 14, 16-24, and 30-33 are under examination.
Rejections Withdrawn
Rejection of claims 14-24 and 31 under 35 U.S.C. 112(b) is withdrawn with applicant amendment to claims and submission of the new sequence disclosure.
Rejection of claims 14-24 and 30 under 35 U.S.C. 112(a) is withdrawn with applicant amendment to claims. The claims now require binding PSMA, 90% homology to instant SEQ ID NO: 1 and the limited combination of CDR sequences provided. One of skill in the art would be able to identify the antigen-binding fragments the applicants had possession and are claiming.
Rejection of claims under Double Patenting is withdrawn with applicant amendment of pending claims and claim by claim analysis of current sequences limiting instant claims and copending claims.
The New Sequence Disclosure corrects the deficiencies noted in the last office action.
New Rejections – Necessitated by Applicant Amendment of Claims
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.
Claims 14, 16-20, and 23-24 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 14 subpart (vi) states “a CDR-H3 comprising SEQ ID NO: 7”. CDR-H3 was already defined in subpart (iii) therefore the metes and bounds of an antibody with 2 CDR-H3 sequences is not clear in view of the art.
Claims 16-20 and 23-24 fail to correct this issue and thus inherit this issue.
For the purposes of prosecution the claim was examined with SEQ ID NO: 7 as CDR-L3 in view of antibodies shown by the specification and in the claims fully defining the variable light chain of the antibodies. Appropriate correction requested.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 21-22 and 30-33 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The claims fully define the variable heavy chain which comprises a single CDR-H3 and does not comprise the CDR-H3 of SEQ ID NO: 3. The metes and bounds of claims 21-22 and 30-33 do not include all the limitations of claim 14 as written.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Rejections Maintained – Updated With Applicant Amendment to Claims
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 14, 16-21, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et. al. Molecular Therapy 18(2):413-420. (2010) (IDS) and Elsasser-Beile (US 8198416 B2) (Of Record).
Instant SEQ ID NO: 1 comprises the CDRs of instant SEQ ID NO: 2, 3, 4, 5, and 6.
Regarding claim 14, Zhong teaches a chimeric antigen receptor (CAR) comprising an anti-PSMA antigen binding fragment, a transmembrane domain, and an intracellular signaling domain (Figure 1).
Regarding claim 19, Zhong teaches chimeric antigen receptors comprising an intracellular signaling domain that is a CD3ζ cytoplasmic domain and a costimulatory domain is CD28 or 4-1BB or a combination of them (Figure 1 and Abstract). These are the elected species for the intracellular signaling domain and costimulatory domain by applicant.
Regarding claims 20-21, Zhang teaches a nucleic acid vector encoding the CAR (Figure 5, page 418 in col 2 in par 1).
Regarding claims 23-24, Zhang teaches the leukapheresis from donor peripheral blood, transducing the cells with a vector that encodes the CAR and isolating then expansion of the transduced cells. The cells being expanded would be transduced T cells encoding the CAR of claim 14 (page 418 in col 2 in par 2).
Zhong teaches combining an anti-PSMA antigen-binding domain with the signaling domains of CD28, CD3ζ, and 4-1BB improves cytokine release, in vivo T-cell survival and tumor elimination (Abstract, Figures 4-6).
Regarding the elected transmembrane domain of CD8alpha of amino acids 520-543 of SEQ ID NO: 17. Zhang does not teach the sequences of its CAR components. Zhang does teach a CD8 transmembrane domain in a CAR (Figure 1).
Zhong does not teach the sequences of claims and Zhong does not teach the antigen-binding fragment is humanized.
These deficiencies are filled by Elsasser-Beile.
Elsasser-Beile teaches antigen binding portions that bind prostate specific membrane antigen on tumor cells linked to cytotoxic agents (Abstract).
Regarding claims 14-15 and 17-18, Elsasser-Beile teaches the scFv D7 of SEQ ID NO: 22 which matches the elected species of instant SEQ ID NO: 1. By teaching SEQ ID NO: 22 Elsasser-Beile teaches the CDRs of claim 15. SEQ ID NO: 22 of Elsasser-Beile matches the sequence of claim 17 at amino acid positions 99 to 112 and the CDR3 of light chain of instant SEQ ID NO: 7 is taught by Elsasser-Beile in SEQ ID NO: 22 in amino acids 233 to 240.
Regarding claim 16, Elsasser-Beile teaches antibodies derived from mouse may cause unwanted immunological side-effects in response to the antibody coming from another species. Elsasser-Beile teaches the antigen binding portions of monoclonal antibodies can be humanized by replacing the mouse framework regions into human framework regions. Elsasser-Beile teaches this maintains the binding properties of the CDRs (col 5 in lines 18-27).
It would have been obvious at the time the application was filed to substitute the anti-PSMA scFv of the CAR of Zhong with the scFv of Elsasser-Beile to produce a CAR comprising an antigen-binding fragment of instant SEQ ID NO: 17, a transmembrane domain, and an intracellular signaling domain. One of ordinary skill in the art would have been motivated as Zhong teaches the combination of an anti-PSMA binding domain with the signaling domains of CD28, CD3ζ, and 4-1BB improves cytokine release, in vivo T-cell survival and tumor elimination and Elsasser-Beile teaches an effective anti-PSMA scFv that can be combined with cytotoxic agents for effective treatment of cancer. There would have been a reasonable expectation of success as the scFv of Zhong and the scFv of Elsasser-Beile are both anti-PSMA scFv for use in larger molecules for inducing cytotoxicity for the elimination of tumors.
Applicant Arguments
Applicant argues amendment of claims to require specific sequences overcomes the obvious style art rejections.
Applicant argues the substitution of the anti-PSMA scFv of Zhong with the scFv of Elsasser-Beile would not be obvious or have an expectation of success given the binding activity of the resulting CAR molecules.
Applicant argues claim 30 not being rejected as evidence for claim 14 being allowable.
Response to Arguments
Applicant's arguments filed 05 September 2025 have been fully considered but they are not persuasive.
The substitution of PSMA binding scFv in a CAR with a PSMA binding scFv is a substitution of similar in the art molecules. One of skill in the art would have known a mouse derived scFv would have improved function as a therapeutical with removal of mouse components not required for antigen binding. It is not surprising to produce a CAR from known antigen binding scFvs.
Regarding pending claim 30, please see statement under Allowable Subject Matter further in this office action. Examiner’s rejections are based on sequence search results and state of the art.
Claims 14, 21-22, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et. al. Molecular Therapy 18(2):413-420. (2010) (IDS) and Elsasser-Beile (US 8198416 B2) (Of Record) as applied to claims 14-21 and 23-24 above, and further in view of June (WO 2016126608 A1) (Of Record).
The teachings of Zhong and Elsasser-Beil from the 103 rejection are incorporated here in full.
As claims 14 and 21 are obvious over Zhong and Elsasser-Beil they would be obvious in further view of June.
Regarding the elected transmembrane domain of CD8alpha of amino acids 520-543 of SEQ ID NO: 17. Zhang does not teach the sequences of its CAR components. Zhang does teach a CD8 transmembrane domain in a CAR (Figure 1).
Zhang does not teach the CD8alpha transmembrane domain in an anti-PSMA CAR.
This deficiency is filled by June.
June teaches engineered T cells that express CARs (Abstract). June teaches the CD8 Transmembrane domain of the elected species in SEQ ID NO: 12 (Table 1 on page 65). June teaches the CAR comprising a CD8 alpha transmembrane domain of SEQ ID NO: 12 (page 140 in lines 14-15 and 25-27). June teaches an anti-PSMA CAR (claims 5 and 17) and teaches the anti-PSMA CAR of claim 17 comprises a transmembrane domain of CD8 alpha (claim 23). June teaches the CD8 transmembrane domains as alternatives that can be used interchangeably (page 101 in lines 26-31 and page 102 in lines 1-2).
It would have been obvious to one of ordinary skill in the art to substitute the general CD8 transmembrane domain of Zhong with the CD8 alpha of June. One of ordinary skill in the art would have been motivated as June teaches the CD8 transmembrane domains can be used interchangeably and teaches the CD8 alpha can be used with in an anti-PSMA CAR. This would in combination with Elsasser-Beile be a CAR comprising instant SEQ ID NO: 11 comprising the scFv of instant SEQ ID NO: 1 taught by Elsasser-Beile, a CD8 alpha transmembrane domain taught by June, an intracellular signaling domain of CD3ζ, and a costimulatory domain of 4-1BB, which is the elected species of the applicant. There would have been a reasonable expectation of success as Zhong and June teach anti-PSMA CAR T cells comprising a CD8 transmembrane domain and June teaches that the CD8 transmembrane domains are equivalents that can be substituted for each other in CAR T cells. This is the CAR of amino acid of SEQ ID NO: 14 required by claim 33.
Applicant Arguments
Applicant did not provide arguments specific for this rejection.
Response to Arguments
Rejection is maintained.
Allowable Subject Matter
Claims 30-32 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.
The variable heavy chains of SEQ ID NO: 21-25 and 33-36 appear free of the art.
Conclusion
No Claims Allowable.
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/F.E./Examiner, Art Unit 1643
/Meera Natarajan/Primary Examiner, Art Unit 1643