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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US2021/018224 filed on 02/16/2021, which claims the benefit of US Provisional Application Nos. 62/976,867 filed on 02/14/2020; 62/978,230 filed on 02/18/2020; and 63/048,090 filed on 07/04/2020. The sequences listed in Claims 2-3 do not have support in US Provisional Application No. 62/976,867. Claims 2-3 do have support in US Provisional Application No. 63/048,090 and receive an effective filing date of 07/04/2020. Claims 1 and 4-5 have support in US Provisional Application No. 62/976,867 and receive an effective filing date of 02/14/2020.
Election/Restriction
Applicant’s election with traverse of Group I (Claims 1-5) and species election:
Neoantigen sequence SEQ ID NO: 19
TCR sequence SEQ ID NO: 1
TIL as a species of T cell
TIL comprising a TCR
PD-1 inhibitor
EGFR family gene
EFGR
Osimertinib
in the reply filed on 10/29/2025 is acknowledged. The traversal is on the grounds that the Office Action did not show that a serious burden would be required to examine all of the claims. This is not found persuasive because a search burden is not considered in the restriction of a 371 international application. An international application should relate to only one invention or, if there is more than one invention, the inclusion of those inventions in one international application is only permitted if all inventions are so linked as to form a single general inventive concept (PCT Rule 13.1). With respect to a group of inventions claimed in an international application, unity of invention exists only when there is a technical relationship among the claimed inventions involving one or more of the same or corresponding special technical features (MPEP § 1850.II). Therefore, a search burden is not considered in the restriction requirement for an international application and the argument is not found persuasive.
Applicant further argues that Groups I and II are directed to a product and a process of use (a T-cell receptor and a method of treating by administering the T-cell receptor), and according to 37 C.F.R. § 1.475(b), the groups have unity of invention. As summarized above, 37 C.F.R. § 1.475(a) states “Where a group of inventions is claimed in an application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression "special technical features" shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art” (emphasis added). It is of record in the restriction requirement filed 05/29/2025 that the shared technical feature (a T cell receptor that recognizes neoantigens) is not a special technical feature as it does not make a contribution over the prior art. Therefore, Groups I and II lack unity of invention, and Applicant’s argument is not persuasive.
Applicant cites MPEP § 808.01(a) to support that examination of all species would not be a burden to the Examiner. As of record in the restriction requirement filed 05/29/2025, the species do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same property or activity, and differ in either structure, class of chemical compound, or disease etiology. PCT Rules 13.1-13.2 do not pertain to a serious search burden but instead require unity of invention, and the species election requirement of record details how the species do not have unity of invention. Applicant’s arguments are not persuasive, and the species election is maintained.
The requirement is still deemed proper and is therefore made FINAL. Please note that after a final requirement for restriction, the Applicants, in addition to making any response due on the remainder of the action, may petition the Commissioner to review the requirement. Petition may be deferred until after final action on or allowance of claims to the invention elected, but must be filed not later than appeal. A petition will not be considered if reconsideration of the requirement was not requested (See § 1.181.).
Claims 6-12 and 15-24 are withdrawn from further consideration pursuant
to 37 CFR 1.142(b), as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim. Election was made with traverse in the reply filed on 10/29/2025.
Claim Status
Claim listing filed on August 12, 2022 is pending. Claims 13-14 are canceled. Claims 3-4, 6, 9-12, 15, 17, and 23-24 are amended. Claims 6-12 and 15-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions or species. Claims 1-5 are examined upon their merits.
Information Disclosure Statement
The information disclosure statements filed on 08/12/2022 and 10/29/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
Paragraph 32 lists Figure 19D, but there is no Figure 19D.
Paragraph 35, line 1 recites "dn" and should be corrected to "and."
Paragraph 61 marks a blank line and not a paragraph.
Paragraph 84, line 1 recites "hen" and should be corrected to "then."
Appropriate correction is required. Applicant is urged to carefully review the specification for additional informalities.
Sequence Compliance in Drawings and Tables
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821 (a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. § 1.821 through 1.825. Specifically, no sequence identification (SEQ ID NO.) has been provided for the amino acid sequences presented in Figures 3-5, 8, and 16 of the drawings. Further, Figure 17 is unintelligible, and it is unclear if it contains sequences. No sequence identification (SEQ ID NO.) has been provided for the amino acid sequences presented in Table 1 on pages 17-19 of the specification. The SEQ ID NOs presented in Table 2 on pages 36-37 of the specification are incorrect. For example, CASRVGIAEAFF is labeled as SEQ ID NO: 39 wherein CASRVGIAEAFF is defined as SEQ ID NO: 1 in the claims and the sequence listing. Applicant is reminded to comply with sequence rules as stated in MPEP§ 2422 and review the specification to ensure the application is in full sequence compliance in response to this action.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claims 1-5 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.
Claim 1 recites “a T cell receptor that recognizes for one or more neoantigens.” Claims 2 and 4-5 are dependent on Claim 1 and do not further define the claimed T cell receptor. This phrase is considered functional language because the feature (the T cell receptor) is defined by what it does (recognizes for one or more neoantigens) rather than by what it is (MPEP § 2173.05(g)). To determine if functional language is ambiguous, the following factors are considered: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim. These factors are examples of points to be considered when determining whether language is ambiguous and are not intended to be all inclusive or limiting (MPEP § 2173.05(g)). Claim 1 recites a result obtained without any required structure for the T cell receptor. The metes and bounds of the T cell receptor cannot be readily determined. Therefore, Claims 1-2 and 4-5 are rejected as being indefinite.
Claims 2-4 recite “the TCR of Claim 1,” but the abbreviation “TCR” is not defined in Claim 1. For the purpose of compact prosecution, “TCR” is interpreted as “T cell receptor.”
A possible correction to overcome the indefinite abbreviation is to recite “A T cell receptor (TCR) that recognizes for one or more neoantigens” in Claim 1. Claims 2-5 are rejected for indefiniteness.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature-based product without significantly more.
The claims are directed to a T cell receptor (TCR) that recognizes one or more neoantigens (Claim 1) and a T cell comprising the TCR (Claim 4) wherein the T cell is a tumor infiltrating lymphocyte (TIL) (Claim 5). Cafri et al. Nature Communications 2019 (of record in IDS) teaches that tumor infiltrating lymphocytes (TILs) are enriched with neoantigen-specific T cells (page 2, paragraph 1). Different approaches can be used to isolate the neoantigen-specific T cells from patient blood and enrich or expand the T cell population (page 2, paragraph 2). Cafri specifically sequenced the neoantigen-specific TCRs from peripheral blood lymphocytes of six epithelial cancer patients with known neoantigen-reactive TCRs that were previously found in their TILs (page 2, paragraph 3). The teachings of Cafri show that TIL T-cells comprising TCRs that recognize neoantigens are naturally produced in human cancer patients.
Claim 2 recites wherein the neoantigen recognized by the TCR comprises SEQ ID NO: 19, and Claim 3 recites wherein the TCR comprises SEQ ID NO: 1. The specification teaches that the neoantigens and TCRs were isolated from cancer patient blood samples and/or tissue resections and sequenced to determine the TCR variable beta chain sequences and their corresponding neoantigens (Example 1, Table 2, and Figure 1).
Therefore, the claims are directed to a product of nature. The TCRs and neoantigens in Claims 2-3 were produced naturally by donor cancer patients, isolated, and sequenced. The general TIL T cells comprising neoantigen-specific TCRs in Claims 1 and 4-5 were known to be naturally-occurring prior to the effective filing date as evidenced by Cafri. It is not clear that any modifications were made to alter the naturally-occurring TCRs and neoantigens.
Considering the flowchart of subject matter eligibility in MPEP § 2106, the claims are directed to a product, which is a statutory category of invention. (Step 1: YES).
Step 2A, Prong One sets forth the markedly different characteristics analysis that the courts use to identify product of nature exceptions (MPEP 2106.04(c)). The analysis requires determining if the claimed product has "markedly different characteristics from any found in nature". Diamond v. Chakrabarty, 447 U.S. 303, 310, 206 USPQ 193, 197 (1980). Not all changes in characteristics rise to the level of a marked difference (MPEP 2106.04(c).II.C.2). In Ambry Genetics, the court identified claimed DNA fragments known as “primers” as products of nature because they corresponded to a naturally occurring double-stranded DNA sequence. The patentee argued that these primers had markedly different structural characteristics from the natural DNA, because the primers were synthetically created and because single-stranded DNA cannot be found in the human body. The court disagreed, concluding that the primers’ structural characteristics were not markedly different than the corresponding strands of DNA in nature, because the primers had the same nucleotide sequences and the same innate functions. University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014).
The naturally-occurring counterpart to the instantly claimed product are neoantigen-targeting TCRs that occur in nature through V(D)J recombination. The instant application did not create a new, non-naturally occurring TCR but instead selected for TCRs of interest in donor patient peripheral blood samples (Example 1 and Table 2). The claimed TCRs have the same structures and innate functions as their naturally-occurring counterparts (Step 2A, Prong One: YES).
The claims fail to recite a practical application of additional elements that integrate the judicial exception into a practical application. The claims, for example, are not directed to using the naturally-occurring TCRs to affect a particular treatment as discussed in MPEP § 2106.04(d)(2). (Step 2A, Prong Two: NO).
Nothing significantly more than the judicial exceptions is recited within the claims. The courts have defined that simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to a judicial exception is not “significantly more” (MPEP § 2106.05.I.A). The courts have recognized using polymerase chain reaction to amplify and detect DNA, detecting DNA in a sample, analyzing DNA to provide sequence information, amplifying and sequencing nucleic acid sequences, and determining the level of a biomarker as routine activities in the life sciences when claimed at a high level of generality (MPEP § 2106.05(d).II).
In Mayo Collaborative Services it was held that:
"Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work." Gottschalk v. Benson, 409 U. S. 63, 67 (1972). And monopolization of those tools through the grant of a patent might tend to impede innovation more than it would tend to promote it. [emphasis added].
Therefore, the claims fail to recite additional elements that amount to significantly more than the product of nature (Step 2B: NO).
Claims 1-5 are directed to a product of nature and are not eligible subject matter under 35 U.S.C. 101.
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)(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.
Claims 1 and 4-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cafri et al. Nature Communications 2019 (of record in IDS).
The instant claims recite a T cell receptor (TCR) that recognizes one or more neoantigens (Claim 1) and a T cell comprising the TCR (Claim 4) wherein the T cell is a tumor infiltrating lymphocyte (TIL) (Claim 5).
Cafri teaches that tumor infiltrating lymphocytes (TILs) are enriched with neoantigen-specific T cells (page 2, paragraph 1). Different approaches can be used to isolate the neoantigen-specific T cells from patient blood and enrich or expand the T cell population (page 2, paragraph 2). Cafri specifically sequenced the neoantigen-specific TCRs from peripheral blood lymphocytes of six epithelial cancer patients with known neoantigen-reactive TCRs that were previously found in their TILs (page 2, paragraph 3). The teachings of Cafri show that TIL T-cells comprising TCRs that recognize neoantigens were known to be naturally produced in human cancer patients prior to the effective filing date of the instant invention.
Therefore, Claims 1 and 4-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cafri.
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.
1. Claims 1-2 and 4-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 16 of copending U.S. App. No. 17/622,375.
The instant claims recite a T cell receptor (TCR) that recognizes one or more neoantigens (Claim 1) and a T cell comprising the TCR (Claim 4) wherein the T cell is a tumor infiltrating lymphocyte (TIL) (Claim 5). The TCR recognizes a neoantigen comprising SEQ ID NO: 19 (Claim 2).
The copending claims are directed to a method of screening neoantigens comprising expanding TILs and co-culturing the TILs with neoantigens wherein reactive TILs confirm the neoantigen status (Claim 1). Claim 5 recites wherein the TIL is specifically a T cell. Claim 16 is directed to a method of treating cancer comprising administering a TIL wherein the TIL is reactive to a neoantigen comprising SEQ ID NO: 19. Note, copending SEQ ID NO: 19 is 100% identical to instant SEQ ID NO: 19.
The copending claims teach neoantigen-specific T cells and TILs, and it is obvious that the binding specificity of the T cells comes from their TCRs. The instant claims are either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
2. Claims 1 and 4-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-4 of copending U.S. App. No. 18/274,875.
The instant claims are recited above.
The copending claims recite a TCR that recognizes for one or more neoantigens (Claim 2) and a T cell comprising the TCR (Claim 3) wherein the T cell is a TIL (Claim 4).
The instant claims are either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
3. Claims 1 and 4-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2 and 4-5 of copending U.S. App. No. 19/120,526.
The instant claims are recited above.
The copending claims recite a TCR that recognizes one or more neoantigens (Claim 2) and a T cell comprising the TCR (Claim 4) wherein the T cell is a TIL (Claim 5).
The instant claims are either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm EST.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/STACEY N MACFARLANE/Examiner, Art Unit 1675