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 .
Election
In response to the Restriction Requirement, Applicant's reply filed on 11/07/2025 without traverse is acknowledged with election of Group I (claims 1, 3, 5, 7, 8, 10, 12, 13, 16-20 and 25), drawn to a T-cell receptor (TCR). In response to the species election requirement, Applicant elects the following species for examination:
α-CDR1: TSGFNG (SEQ ID NO:39);
α-CDR2: NVLDGL (SEQ ID NO:40);
α-CDR3: AVRGWSDGQKLL (SEQ ID NO:45);
β-CDR1: SGHRS (SEQ ID NO:42);
β-CDR2: YFSETQ (SEQ ID NO:43);
β-CDR3: ASSLGQGGKDEQY (SEQ ID NO:44);
α chain variable domain: SEQ ID NO: 13;
β chain variable domain: SEQ ID NO: 2;
one or more groups of two amino acid positions for substitution by cysteine residues for the artificial disulfide bond contained between the α chain constant region and the β chain constant region of the TCR: Thr48 of TRAC*01 exon 1 and Ser57 of TRBC1*01 or TRBC2*01 exon 1.
Claims 21-24, 26 and 28 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to non-elected inventions.
Status of Claims
Claims 1, 3, 5, 7, 8, 10, 12, 13, 16-26 and 28 are currently pending.
Claims 1, 3, 5, 7, 8, 10, 12, 13, 20, 21, 23-26 and 28 are amended.
Claims 21-24, 26 and 28 are withdrawn.
Claims 1, 3, 5, 7, 8, 10, 12, 13, 16-20 and 25 are currently under examination on the merits.
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. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The U.S. effective filing date of all claims under examination is therefore set at 03/20/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/19/2022 and 06/24/2-25 are being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
Claims 1, 3, 5, 7, 8, 10, 12, 13, 16-20 and 25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AlA), 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-AlA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 3, 5, 7, 8, 10, 12, 13, 16-20 and 25 are rejected because independent claim 1, as well as dependent claims 3, 5, 8, 10, 13, 16, 17, 18 and 19 recite the word “preferably”, and in claims 13 and 18 the claims further recite the phrase “more preferably”. The metes-and-bounds of the claims are unclear because it is unclear how, or if, possible limitations following “preferably” and “more preferably’ limit the claims. Description of preferences should be properly set forth in the specification rather than the claims. If stated in the claims, preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph should be made. The Examiner should analyze whether the metes and bounds of the claim are clearly set forth. Examples of claim language which have been held to be indefinite are (A) "a temperature of between 45 and 78 degrees Celsius, preferably between 50 and 60 degrees Celsius"; and (B) "a predetermined quantity, for example, the maximum capacity."
Claim 18 recites “….a flexible short peptide sequence (linker)” in line 4. The word “linker” in parenthesis is taken as an example for “a flexible short peptide sequence”. Examples in a claim renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is suggested that the claim be amended to “a flexible short peptide linker sequence” to obviate this rejection.
Claim Rejections 35 U.S.C.112(a)
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 1, 3, 5, 7, 8, 10, 13, 16-20 and 25 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the instant case, the claims are inclusive of a genus of T-cell receptors (TCRs) that bind the KWVESIFLIF (SEQ ID NO: 38)-HLA-A2402 complex and comprise a TCRα chain variable domain comprising an amino acid sequence having at least 90% of sequence homology with an amino acid sequence as shown in SEQ ID NO: 1, and a TCRβ chain variable domain comprising an amino acid sequence having at least 90% of sequence homology with an amino acid sequence as shown in SEQ ID NO: 2. However, the written description in this case only sets forth twenty-one species named TCR No(s). 1 to 21, as recited in the table of claim 17, wherein the TCRα chain variable domain comprises amino acid sequence as shown in one of SEQ ID NOs: 1 and 13-29, and the TCRβ chain variable domain comprises amino acid sequence as shown in one of SEQ ID NOs: 2 and 30-33. To further confirm this, on Pg. 27-28 Table 1 and Pg. 42 Table 2, the specification teaches the same twenty-one TCRs with the same TCRα chain variable domain and TCRβ chain variable domain combinations as recited in claim 17. Therefore, only twenty-one TCRs were made and shown to bind the KWVESIFLIF (SEQ ID NO: 38)-HLA-A2402 complex. The specification does not disclose, and the art does not teach, the genus of TCRs as broadly encompassed in the claims.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNA, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus.”
The inventions at issue in Lilly were DNA constructs per se, the holdings of that case is also applicable to claims such as those at issue here.
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of species antigen binding proteins that encompass the genus of antigen binding proteins comprising an antigen binding domain that binds to Von Willebrand factor (VWF) under shear gradient conditions nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
Since the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure of TWENTY-ONE SPECIES found in the specification is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, even though Applicant may propose methods of screening for possible members of the genus, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolation. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. See Ariad, 94 USPQ2d at 1161; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 102 / 35 USC § 103
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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 1 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Ozawa et al. (Biochemical and biophysical research communications. 2008 Mar 21;367(4):820-5; provided on the International Search Report and on the IDS submitted 09/19/2022).
Ozawa et al. teaches TCR Vα chain with ID of BAF94370 and TCR Vβ chain of BAF94926 that have 96% and 95% identity to instant SEQ ID NO: 1 and 2 (see left column on page 821 stating sequences have been deposited in GenBank Accession Nos.).
Sequence alignment of instant SEQ ID NO: 1 (top) with Ozawa et al. BAF94370 (bottom)
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190
717
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Greyscale
Sequence alignment of instant SEQ ID NO: 2 (top) with Ozawa et al. BAF94926 (bottom)
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184
650
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Greyscale
While Ozawa et al. teaches the TCR with amino acid sequences of BAF94370 for the Vα chain and BAF94926 for the Vβ chain that are greater than 90% homology to instant SEQ ID NOs: 1 and 2 respectively, they do not teach the recited binding function. However, the TCR appears to be the same absent a showing otherwise because the TCR of Ozawa et al. has TCR Vα chain and Vβ chain consisting of amino acid sequences greater than 90% sequence homology with instant SEQ ID NOs: 1 and 2.
Allowable Subject Matter
The TCRα chain variable domain sequence as set forth in SEQ ID NO: 13 and the TCRβ chain variable domain sequence as set forth in SEQ ID NO: 2 are free of prior art. Likewise, the α-CDR1: TSGFNG (SEQ ID NO:39), α-CDR2: NVLDGL (SEQ ID NO:40), α-CDR3: AVRGWSDGQKLL (SEQ ID NO:45), β-CDR1: SGHRS (SEQ ID NO:42), β-CDR2: YFSETQ (SEQ ID NO:43), and β-CDR3: ASSLGQGGKDEQY (SEQ ID NO:44) are free of prior art.
In an effort to expedite prosecution, the Examiner proposes amendment of claim 1 to include the allowable subject matter such that claim 1 recites “A T-cell receptor (TCR), wherein the TCR comprises a TCRα chain variable domain and a TCRβ chain variable domain and has an activity of binding to KWVESIFLIF (SEQ ID NO: 38)-HLAA2402 complex, and the TCRα chain variable domain comprises the amino acid sequence as shown in SEQ ID NO: 13, and the TCRβ chain variable domain comprises an amino acid sequence as shown in SEQ ID NO: 2”.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yie-Chia Lee (Tonya) whose telephone number is (571)272-0123. The examiner can normally be reached Monday - Friday 7.30a - 3.30p Eastern Time Zone.
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/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642