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 .
Claims 1-28 are pending.
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.
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 1-28 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 pre-AIA the applicant regards as the invention.
Claim 1, 11, 10 recite or encompass the preamble limitation of “optimizing the TCR” which is confusing and ambiguous because it is not clear where in the body of the claim the preamble stated purpose is fulfilled. All claims encompass the term.
Claims 1-28 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a TCR comprising the SEQ ID NO: of the specific CDRs, does not reasonably provide enablement for a variant TCR without sequence identified. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The first paragraph of § 112 requires that the patent specification enable "those skilled in the art how to make and use the full scope of the claimed invention without `undue experimentation."' Genentech, Inc. v. Novo Nordisk AIS, 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)); see also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). ("[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art."). Whether making and using the invention would have required undue experimentation, and thus whether the disclosure is enabling is a legal conclusion based upon several underlying factual inquiries. See In re Wands, 858 F.2d 731, 735, 736-37, 8 USPQ2d 1400, 1402, 1404 (Fed. Cir. 1988). As set forth in Wands, the factors to be considered in determining whether a claimed invention is enabled throughout its scope without undue experimentation include the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, and the breadth of the claims.
Likewise, in Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991), the court affirmed the holding of invalidity of claims to analogs of the EPO gene under § 112 for lack of enablement where applicants had claimed every possible analog of the EPO gene but had disclosed only how to make EPO and a very few analogs. "[D]espite extensive statements in the specification concerning all analogs of the EPO gene that can be made, there is little enabling disclosure of the particular analogs and how to make them .... There may be many other genetic sequences that code for EPO-type products. Amgen has told how to make and use only a few of them and is therefore not entitled to claim all of them." Id., 927 F.2d at 1213-14, 18 USPQ2d at 1027.
Claims encompass a variant CDRs of the TCR without identification of the sequence of CDRs. As written, the claims encompass variant TCR with less than the full complement of CDRs regions which causes the TCR to not function. Claims encompass generic substitutions of amino acids in the CDRs which are critical for binding function. It is well established in the art that the formation of an intact TCR interaction site generally requires the association of the a specific CDR of a given TCR. The three CDRs each of alpha and beta chain are critical to provide the majority of the contact residues for the binding of the TCR to its target peptide (Smith et al., 2014). The amino acid sequences and conformations of each of the chains’ CDRs are critical in maintaining the binding specificity and affinity which is characteristic of a given TCR. It is expected that all of the chains CDRs in their proper order and in the context of framework sequences, which maintain the required conformation of the CDRs are required in order to produce a protein having binding function; and further, that proper association of the chains variable regions is required in order to form functional binding sites .
Due to the large quantity of experimentation necessary to determine which TCR comprising less than the full complement of CDRs would bind, the lack of direction/guidance presented in the specification regarding same, the absence of sufficient working examples directed to same, the complex nature of the invention, the state of the prior art establishing that formation of an intact binding site of TCR routinely requires the association of the complete two chain variable regions each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the TCR to its target site, and the breadth of the claims which fail to recite the requirement for a full complement of 6 CDRs, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Therefore, based on the above Wands analysis, a preponderance of the evidence supports a conclusion that one skilled in the art would not have been enabled to make and use the invention of claims without undue experimentation.
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.
Claim(s) 1-2, 4-7, 9-10, 11-12, 15-16, 18-19, 20-21, 24-25, 27-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Babb et al. (SU 2021/0403527) in view of Liu et al. (US 2019/0382504).
Babb et al. teach the method of tranducing the cell with polynucleotide encoding TCR comprising CDR 1-3 which bind NY-ESO-1 and HLA complex (para 132, 144, 158, 161, 177, 178, 185, 227, 233, 279-284, 297-299; claims 23-26, 31-41, 63-68, 89-91). Babb teach the method wherein the TCR has variability in the alpha and beta chain at CDR 1 and 3 (claim 5; para 213, 228-229) and NY-ESO-1 is the target (claims 1-19, 45-61). The T cells are co-cultured with T2 cells pulsed with HY-ESO-1 (para 233). The T cells are sorted with fluorescence FACS and MFI values (para 90, 209, 285-286, 317, 333-335, 355, 601, 621). The T cells are sorted (para 184, 285-286, 317, 333-335) including FACS (para 317). The activation TCRs are compared (para 11-13, 71, 92, 161, 264; Claim 1-8). Babb teach the method of using MART-1 in combination with TCRs (para 311). The cysteine substitution is optional (para 213, 228; claim 5). Babb does not teach the MFI.
Liu et al. teach the T cells are sorted with fluorescence FACS and MFI values (para 90, 209, 601, 621).
It would have been obvious to one of ordinary skill in the art the time of the filing to incorporate the MFI of Liu into the assays of TCR cell of Babb. One of ordinary skill in the art would have been motivated by increased sensistivity of the MFI.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL D PAK whose telephone number is (571)272-0879. The examiner can normally be reached on flexible time.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL D PAK/Primary Examiner, Art Unit 1674
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