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 .
1. Formal Matters
A. Applicant’s election of Group I, drawn to the species of PD1, in the reply filed on 7/31/26 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)). Therefore, this restriction is deemed proper and is made FINAL.
B. Claims 25-38 are pending. Claims 33-38 are withdrawn as being drawn to non-elected inventions. Claims 25-32 are the subject of this Office Action.
2. Claim Rejections - 35 USC § 112(b)
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 25 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.
The preamble of the claim is drawn to a method of “identifying” a common TCR. However, step (b) recites simply “selecting” a TCR. It is unclear if “identifying” and “selecting” are the same (in other words, is the method complete. While it appears that the terms are interchangeable in this instance, it is unclear if the instant method is complete, or requires other steps. Claims
3. 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 (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 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.
A. Claims 25-28, 31 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Jin-Huan et al. (reference 1 on the IDS filed 1/16/24).
Claim 25 is drawn to a method for identifying a common tumor-specific TCR by obtaining their sequences from at least 2 patients. Claim 26 adds various steps drawn to general TCR nucleic acid isolation from tumor cells collected from a sample, grouping those that are essentially identical into a clonotype group and determining the frequency of tumor TCR nucleic acid samples, including determining CDR3 sequences. The method is additional performed in non-tumor tissue samples and the results compared.
Jin-Huan teaches a method of using a high-throughput screening method to identify TCR sequences in order to characterize the T cell repertoires from cancer patients. Jin-Huan concluded that the several clonotypes uniquely detected in CC patients tended to share similar CDR3 motifs. Jin-Huan concluded that these findings suggest that “TCR repertoire may be a potential indicator of immune monitoring and may be a biomarker for predicting the prognosis of CC patients” (Abstract). The comparison to a non-tumor tissue sample from the patients would have been obvious since it is essentially collecting the desired sample and comparing to a control to obtain baseline measurements.
Regarding claims 27 and 28, it would have been obvious to have used the same tissue type from all the patients in order to most accurately/meaningfully compare the results.
Regarding claims 26 and 31, it would have been obvious to have chosen a frequency the researcher believed would have been indicative of a desirable TCR clonotype depending on the question(s) to be answered. The researcher would have chosen a cutoff limit/value in order to draw conclusions from the data with regard to the purpose of the experiment(s). In addition, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 454, 105 USPQ 223,235, (CCPA 1955). Furthermore, "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and, therefore, obvious) and E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018) (“it is not inventive to discover the optimum or workable ranges by routine experimentation.”).
Regarding claim 32, since T cell activation begins upon the cell’s TCR binding to a foreign peptide bound to an MHC on an antigen-presenting cell.it would have been obvious at the time of the instant invention to have used as assay to measure activation to pharmacologically characterize and ensure a functional TCR.
B. Claims 29 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Jin-Huan et al. in view of Tiercy. The teachings of Jin-Huan are seen in paragraph A of this section. Jin-Huan does not teach HLA. However, Tiercy does teach the importance of HLA in donor compatibility for the treatment of certain conditions and to limit host immune response (e.g. GVHD). Therefore, it would have been obvious at the time of the instant invention to have determined HLA type in order to further characterize the TCRs for potential therapeutic use.
C. Claims 25-28, 31 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Pasetto et al. (reference 2 on the IDS filed 1/19/26) in view of Jin et al.
Pasetto teaches a method of obtaining tumor-reactive T cells by using a bulk population of T cell clonotypes is samples from cancer patients (paragraph [0004]). Pasetto also teaches sequencing of the CDRs, including CDR3 ([0004], [0044]). Figure 4B teach the frequency of the TCR clonotypes in T cell populations.
Pasetto does not teach selecting non-tumor cells. However, Jin does teach methods of sequencing for TCR repertoire profiling on matched tumor/adjacent normal tissue (i.e. non-tumor) from 15 patients (Abstract). Neither reference specifically teaches identifying a common tumor-specific epitope. However, given the teachings of both Pasetto and Jin, which demonstrate TCR repertoire profiling, it would have been obvious to have compared the data in order to drawn conclusions with regard to TCR expression. The artisan would have immediately identified commonalities among patients.
Neither reference teaches a specific frequency for each tumor TCR. However, regarding claims 26 and 31, it would have been obvious to have chosen a frequency the researcher believed would have been indicative of a desirable TCR clonotype depending on the question(s) to be answered. The researcher would have chosen a cutoff limit/value in order to draw conclusions from the data with regard to the purpose of the experiment(s). In addition, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller. See also In re Boesch.
Regarding claim 32, since T cell activation begins upon the cell’s TCR binding to a foreign peptide bound to an MHC on an antigen-presenting cell.it would have been obvious at the time of the instant invention to have used as assay to measure activation to pharmacologically characterize and ensure a functional TCR.
D. Claims 29 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Pasetto et al.in view of Jin et al. further in view of Tiercy et al.
The teachings of Pasetto and Jin are seen in paragraph C of this section. Neither teaches HLA. However, Tiercy does teach the importance of HLA in donor compatibility for the treatment of certain conditions and to limit host immune response (e.g. GVHD). Therefore, it would have been obvious at the time of the instant invention to have determined HLA type in order to further characterize the TCRs for potential therapeutic use.
4. Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 25-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1-3 of copending Application No. 18/757,588 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are essentially drawn to the same subject matter (e.g. obtaining, aligning and grouping TCRs based on their nucleic acid sequences). The main difference being that the instant claims compare the isolated TCRs (clonotypes) between 2 or more subjects in order to find those TCRs common among the subjects.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
5. Conclusion
No claim is allowable.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647
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