The examiner of this application in the PTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Peter Johansen, Group Art Unit 1642, Technology Center 1600.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 March 2, 2026 has been entered. By way of this submission, Applicant has amended claim 60.
Claims 60-61, 66-67, 74-78, and 87-95 are pending in the application and under examination before the Office.
The rejections of record can be found in the previous Office action, dated September 2, 2025.
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.
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.
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.
Claims 60-61, 66-67, 74-75, and 87-95 are rejected under 35 U.S.C. 103 as being unpatentable as being unpatentable over Olivares (WO2015123642A1) in view of Balderes (WO2009114585A1) and Houghton (WO199640249).
Olivares teaches a chimeric antigen receptor (CAR) that binds GP75 (also known as Trp1 and TYRP1, see page 20 of the instant specification), based upon a binding domain TA99 (Table 1, para. 0021). Applicant's specification states that the scFv used is based on TA99 (see pages 24 and 65 of the instant specification).
Olivares further teaches said CAR comprises an extracellular antigen-binding domain, a transmembrane domain and an endodomain (i.e., an intracellular domain) (para. 0023).
Olivares further teaches that said CAR and cells and pharmaceutical compositions comprising such are useful for treating cancer (para. 0005 and 0073), and are useful in killing tumor cells (para. 0002), which is pertinent to claim 61.
Olivares further teaches that the cancer is melanoma, and the subject is human (para. 0015), which is pertinent to claims 66-67 and 74.
Olivares further teaches that said CAR may be expressed in T cells (e.g., para. 0009), which is pertinent to claim 75.
Olivares further teaches that the extracellular antigen-binding domain may be an scFv (para. 0008 and 0086), which is pertinent to claim 87.
Olivares further teaches that the transmembrane domain may be a CD8 domain (para. 0083 and 00126), which is pertinent to claims 88-89.
Olivares further teaches that the intracellular domain may be a CD3zeta domain (para. 0008, 0022, 00114 and 00130), which is pertinent to claim 90.
Olivares further teaches that the intracellular domain may also comprise a CD28 co-stimulatory domain (para. 0008 and 0084), which is pertinent to claims 91-93.
Olivares further teaches that the T cell expressing the above CAR may be an NKT cell (para 0014), which is pertinent to claim 95.
However, Olivares does not teach the claimed sequences of the antigen-binding domain.
Balderes teaches antibodies that bind to TYRP1 with identical complementarity determining regions to that of a humanized version of TA99 (CTA99) (page 3, line 28 through page 4, line 7, and page 24, line 21-29). These complementarity determining regions are enumerated as SEQ ID NOs: 7-12 in Balderes, and are identical to the complementarity determining regions of the chimeric antigen receptor antigen-binding domain used in the claimed method (see Applicant's SEQ ID NOs: 1-6).
Balderes further teaches scFvs of the above antibody (page 9, line 17 through page 10, line 4).
Balderes further teaches that antibodies substantially homologous to CTA99 can be readily designed and manufactured utilizing various recombinant DNA techniques well known to those skilled in the art (page 11, line 29 through page 12, line 7).
Balderes further teaches that CTA99 is effective at treating human melanoma (page 30, lines 4 through page 32, line 17).
Houghton teaches that antibody TA99 is useful in treating melanoma (e.g., Figure 1).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Olivares, Balderes, and Houghton to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since all of Olivares, Balderes, and Houghton are concerned with using the anti-Trp1 antibody TA99 for the treatment of melanoma. Starting with the method of treatment using CAR-T cells based upon the TA99 scFV taught by Olivares, one of ordinary skill could follow guidance in both Balderes and Houghton concerning the TA99 antibody to arrive at the claimed method. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
While the references do not explicitly teach the claimed light and heavy chain sequences, Applicant's specification states that the scFv used is based on TA99, as described in the Houghton reference (see pages 24 and 65 of the instant specification). As Houghton discloses TA99, the light and heavy chain sequences of this antibody must also be present. The ordinary artisan using the TA99 antibody or scFV would also inherently be using the same sequences.
Furthermore, Balderes teaches an exemplary scFv with complementarity determining regions that are identical to the complementarity determining regions of the chimeric antigen receptor antigen-binding domain used in the claimed method. Balderes also teaches that antibodies substantially homologous to CTA99 can be readily designed and manufactured utilizing various recombinant DNA techniques well known to those skilled in the art. It would therefore be obvious to utilize these correctly defined CTA99 CDR regions in a chimeric antigen receptor which is directed to the TYRP1 protein for the purposes of utilizing the correct, previously heterogeneously defined VL "TA99" which has improved activity and a higher affinity for the TYRP1 molecule to create a more effective antigen binding chimeric antigen receptor molecule as described by Balderes.
Applicant argues that the skilled artisan, in view of the common knowledge in the art, would not have been motivated to develop a method of treating cancer targeting Trp1, as such treatment were known to show failure of treatments and off-target toxicities, citing reference to Muranski (Blood, The Journal of the American Society of Hematology, 112.2 (2008): 362-373). Applicant further argues that Balderes states that the unacceptably toxicity of TA99 would make it unacceptable for use as a therapeutic in humans.
Applicant's arguments have been considered fully but are not found to be persuasive.
Muranski teaches a T cell which binds through an engineered T cell receptor. Balderes teaches only an antibody. Neither of these references teaches chimeric antigen receptors.
Furthermore, contrary to Applicant's assertion, Muranski teaches that Th17-polarized TRP-1 cells are highly efficient in mediating the rejection of established B16 melanoma tumor upon adoptive cell transfer (Figure 4).
Balderes is also explicit that TA99-based treatments are useful in the treatment of melanoma (page 5, lines 6-11, also see page 30, lines 4-16).
Balderes also teaches that TA99 can be modified for more suitable use in humans (page 24, lines 28-29). The guidance of Balderes would direct one of ordinary skill to make humanized versions of TA99 that solve the problem of any toxicity in targeting Trp1.
It is also noted that this argument was not found persuasive in the previous Office action, dated September 2, 2025.
Applicant's arguments also raise questions of enablement, since the CAR construct used in the claimed method is based upon TA99 and targets Trp1, and Applicant has not explained why their method is free from the asserted problems of other such methods replying upon targeting Trp1.
This rejection is therefore maintained.
Claims 76-78 are rejected under 35 U.S.C. 103 as being unpatentable over Olivares, Balderes and Houghton as applied to claim 60 above, and further in view of June (WO2012079000).
The teachings of Olivares, Balderes and Houghton have been described supra. However, Olivares, Balderes and Houghton do not teach administering cyclophosphamide.
June teaches a method of treating a cancer, comprising administering a CAR-T cell therapy (e.g., page 5, lines 21-34).
June further teaches that the CAR may target TRP-1 (page 29, line 18).
June further teaches that the cancer to be treated may be melanoma (page 50, line 16).
June further teaches that the CAR-T therapy may be administered in combination with cyclophosphamide (page 55, lines 15-20).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Olivares, Balderes, Houghton, and June to arrive at the claimed invention. As stated above, CAR-T treatments for melanoma using Trp-1 targeting antigen-binding domains were known, according to Olivares, Balderes and Houghton. June teaches that cyclophosphamide may be administered in combination with CAR-T treatment. One of ordinary skill would therefore be motivated to combine the cyclophosphamide of June with the CAR-T cell of Olivares, Balderes and Houghton. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
Applicant argues that June does not remedy the alleged deficiencies of Olivares, Balderes and Houghton. This is not found persuasive, for reasons described supra.
This rejection is therefore maintained.
Conclusion
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644