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 .
Applicant's arguments filed 8/5/2026 have been fully considered but they are not persuasive.
Claims 1-2 have been cancelled.
The rejection of claim 1 under 35 U.S.C. 102(a)(1) as being anticipated by Border et al. (November 2018, of record) is withdrawn in view of the cancellation of this claim.
The rejection of claims 1-2 under 35 U.S.C. 103 as being unpatentable over Jooss et al. (WO 2019/036688, published 21 February 2019, filed 17 August 2018, of record) in view of Border et al. is withdrawn in view of the cancellation of these claims.
Claim Objections
Claims 14-15 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from another multiply dependent claim. In addition, claims must be dependent in the alternative only. Claim 10 is a multiple dependent claims depending upon claims 3 and 7. Claims 14-15 are multiple dependent claims that depend upon claim 10. See MPEP § 608.01(n). Accordingly, the claims 14-15 have not been further treated on the merits.
Election/Restrictions
Claims 10-13 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claims 10-12 are directed to nucleic acids, vectors, and host cells. Claim 13 is directed to an antibody against a TCR. These products are patentably distinct from the isolated TCR recited in original claim 1. The original claims lacked unity of invention as art could be applied against claims 1-2. There was no special technical feature. Claim 3 as currently amended requires no particular structure for the TCR and lacks a special technical feature as well. In addition, art can be applied against this claim.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 10-13 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
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.
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 3, 4, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Jooss et al. (WO 2019/036688, published 21 February 2019, filed 17 August 2018, of record) in view of Border et al., and Jakobsen et al. (U.S. Patent Application Publication 2006/0155115).
Claim 79 of Jooss et al. is directed to an isolated antigen binding protein directed to an HLA-PEPTIDE target from Table A. An antigen binding protein (ABP) includes T cell receptors (TCR) and antigen binding portions thereof. See at least paragraph [0092]. The TCR CDR can be determined by known numbering schemes. See at least paragraph [0104]. SEQ ID NO: 2133 in Table A is SLLKFLAKV (i.e. identical to instant SEQ ID NO: 1), a fragment of the target MAGE-A10 with HLA of HLA-A*02:01, HLA-A*02:03, HLA-A*02:04, and HLA-A*02:07. SEQ ID NO: 2134 is SLLKFLAK, a fragment of instant SEQ ID NO: 1, a fragment of the target MAGEA10 with HLA-A*03:01. See Table A on page 296. Claim 139 is directed to an engineered cell expressing a receptor comprising the antigen binding protein of any of the preceding claims (including claim 79). Claim 140 depends upon claim 139 and is directed to a T cell. Multispecific ABP are disclosed. See at least paragraph [0114]. The TCR can be part of a chimeric antigen receptor (i.e. a polypeptide comprising a functional portion of the TCR. See at least paragraph [0014]. The TCR can be part of a fusion protein such as being fused to a toxin. See at least paragraph [0271-0272].
Border et al. teaches methods for identifying T cell receptors (TCR) specific for MAGE-A10 epitopes. See at least materials and methods section on page 9.
Jakobsen et al. discloses making multivalent TCR complexes using by multimerization. The multivalent T cell receptor complexes can be used to deliver therapeutic agents or for detecting MHC-peptide complexes. See at least abstract and claims.
It would have been obvious to identify and isolate a T cell receptor which specifically recognizes SEQ ID NO: 2133 (instant SEQ ID NO: 1) or SEQ ID NO: 2134 (a fragment of instant SEQ ID NO: 1) as suggested by Jooss et al. by using the methods of Border et al. One would have been motivated to do so in order to develop new T cell receptors for use in therapeutic applications. Jooss et al. suggest multispecific ABP where the ABP can be a TCR. It would have been obvious and routine to create a multivalent TCR complex according to Jakobsen et al. One would have been motivated to do for the advantages disclosed by Jakobsen et al.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 3-4 and 6-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 3 is directed to an isolated TCR specific for MAGEA10, wherein the TCR specifically recognizes the HLA-A2 bound form of the amino acid sequence of SEQ ID NO: 1 or a fragment thereof. Note that a fragment of SEQ ID NO: 1 includes a single amino acid.
Claim 4 is directed to an isolated TCR according to claim 3 wherein the TCR specifically recognizes the amino acid sequence of SEQ ID NO: 1, which is presented by a molecule encoded by a gene selected from the group consisting of HLA-A*02:01 and HLA-A*02:04, preferably wherein the TCR specifically recognizes the amino acid sequence of SEQ ID NO: 1, which is presented by the HLA-A*02:01 encoded molecule.
Claim 6 is directed to an isolated TCR according to according to claim 3 wherein the TCR comprises a variable TCR a region having an amino acid sequence which is at least 80% identical to SEQ ID NO: 8 and a variable TCR b region having an amino acid sequence which is at least 80% identical to SEQ ID NO: 9.
Claim 7 is directed to an isolated polypeptide comprising a functional portion of the TCR according to claim 3, wherein the functional portion comprises at least one of the amino acid sequences of SEQ ID NOs: 4 and 7, preferably wherein the functional portion comprises the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7.
Claim 8 is directed a multivalent TCR complex comprising at least two TCRs as claimed in claim 3.
Claim 9 is directed to an isolated TCR according to claim 3, polypeptide according to claim 7, multivalent TCR complex according to claim 8, wherein IFN-g secretion is induced by binding to the amino acid sequence of SEQ ID NO: 1, which is presented by the HLA-A*02:01 encoded molecule.
The genus of TCR having the recited properties is not adequately described. The specification discloses the TCR having an α-chain of SEQ ID NO: 8 and a β-chain of SEQ ID NO: 9. SEQ ID NO: 8 contains the CDRs of SEQ ID NOS: 2, 3, and 4. SEQ ID NO: 9 contains the CDRs of SEQ ID NOS: 5, 6, and 7. This TCR recognizes SEQ ID NO: 1. See at least specification pages 9-10. No other TCR are disclosed. The single TCR disclosed is insufficient to describe the genus of claims 3 and 8, particularly for fragments of SEQ ID NO: 1 that include single amino acids or dipeptides, tripeptides, etc.
The specification and claims draw a fence around a perceived genus but the genus is not adequately described. No reasonable structure-function correlation has been established that is commensurate in scope with the claims. The specification does not describe representative examples to support the full scope of the claims.
In particular, claim 6 recites “at least 80%” identical to SEQ ID NOS: 8 and 9; however, these sequences are not required to retain the CDRs required for binding the HLA-A2 bound form of SEQ ID NO: 1.
At least for example, SEQ ID NO: 36 of Schmitt et al. (U.S. Patent No. 12,448,430) has 91% sequence identity with instant SEQ ID NO: 8; however, this TCR chain does not bind the HLA-A2 bound form of instant SEQ ID NO: 1. SEQ ID NO: 36 is a p37-specific TCR α-chain. See at least column 25, lines 37-54, of Schmitt et al.
Alignment of instant SEQ ID NO: 8 (Qy) to SEQ ID NO: 36 (Db) of Schmitt et al.:
Query Match 91.1%; Score 668.5; Length 140;
Best Local Similarity 91.4%;
Matches 128; Conservative 4; Mismatches 7; Indels 1; Gaps 1;
Qy 1 MAMLLGASVLILWLQPDWVNSQQKNDDQQVKQNSPSLSVQEGRISILNCDYTNSMFDYFL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAMLLGASVLILWLQPDWVNSQQKNDDQQVKQNSPSLSVQEGRISILNCDYTNSMFDYFL 60
Qy 61 WYKKYPAEGPTFLISISSIKDKNEDGRFTVFLNKSAKHLSLHIVPSQPGDSAVYFCAANS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||:
Db 61 WYKKYPAEGPTFLISISSIKDKNEDGRFTVFLNKSAKHLSLHIVPSQPGDSAVYFCAASG 120
Qy 121 NSG-YALNFGKGTSLLVTPH 139
| | ||:||||:| |:
Db 121 TGGSYIPTFGRGTSLIVHPY
At least for example, SEQ ID NO: 9 of Ellinger et al. (U.S. Patent No. 12,344,654) has 94% sequence identity with instant SEQ ID NO: 9; however this TCR chain does not bind the HLA-A2 bound form of instant SEQ ID NO: 1. SEQ ID NO: 9 is a MAGE-A4-specific TCR β-chain. See at least abstract and column 12, lines 43-53, of Ellinger et al.
Alignment of instant SEQ ID NO: 9 (Qy) to SEQ ID NO: 9 (Db) of Ellinger et al.:
Query Match 94.3%; Score 650; Length 135;
Best Local Similarity 94.1%;
Matches 127; Conservative 1; Mismatches 3; Indels 4; Gaps 1;
Qy 1 MASLLFFCGAFYLLGTGSMDADVTQTPRNRITKTGKRIMLECSQTKGHDRMYWYRQDPGL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MASLLFFCGAFYLLGTGSMDADVTQTPRNRITKTGKRIMLECSQTKGHDRMYWYRQDPGL 60
Qy 61 GLRLIYYSFDVKDINKGEISDGYSVSRQAQAKFSLSLESAIPNQTALYFCATGD----PL 116
|||||||||||||||||||||||||||||||||||||||||||||||||||| |
Db 61 GLRLIYYSFDVKDINKGEISDGYSVSRQAQAKFSLSLESAIPNQTALYFCATSDWDRSGD 120
Qy 117 QETQYFGPGTRLLVL 131
:||||||||||||||
Db 121 KETQYFGPGTRLLVL 135
Claim 6 provides insufficient structure to adequately describe the genus of the claimed TCR.
Claim 7 requires only one of SEQ ID NO: 4 or 7. These sequences are insufficient to define the genus of the claimed TCR.
With respect to claim 9, the specification does not provide a reasonable structure-function correlation for the genus of TCRs in claims 3, 7, and 8 that induce IGF-g secretion as recited in the claim. This genus is not adequately described.
The claimed isolated TCR are not adequately described.
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 4-5, 7, and 9 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.
Regarding claims 4 and 7, the phrase “preferably” renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 7 recites a “functional portion of the TCR” without making clear what function must be retained. The metes and bounds of the claim cannot be determined.
Claim 5 lacks a conjunction (e.g. “and”) between the TCR a chain limitations and the TCR b chain limitations. It appears applicant intended that both must be present but it is possible that the alternative was meant to be included. Clarification is requested.
Claim 9 is directed to an isolated TCR. However, it depends in part from claim 7 (directed to an isolated polypeptide) and claim 8 (directed to a multivalent TCR complex). The claim is confusing as the product of claim 9 requires less structure than the embodiments of claims 7 and 8 upon which it depends. It does not include all of the limitations of the claims upon which it depends.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
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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.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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