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 .
The Amendments and Remarks filed 8/26/26 in response to the Office Action of 2/27/26 are acknowledged and have been entered.
Claims 336-359 are pending.
Claims 336-345 and 357-359 have been amended by Applicant.
Claims 336-359 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
The rejection under 35 U.S.C. 102(a)(1) is withdrawn.
The rejection under 35 U.S.C. 101 is withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 112
Claims 336-357 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 TCRs comprising TCR-a and TCR-b polypeptides comprising as little as a single CDR. However, the written description in this case only adequately sets forth the following six TCRs encompassed by the claims:
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 5-7 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 19-21;
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 12-14 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 19-21;
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 90-92 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 97-99;
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 104-106 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 111-113;
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 118-120 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 125-127; and
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 132-134 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 139-141.
The specification does not disclose, and the art does not teach, the genus as broadly encompassed in the claims.
The skilled artisan recognizes that, in general, alpha and beta chains (TCR-a and TCR-b polypeptides) comprising six distinct CDR sequences are required to create the TCR peptide-MHC binding site. In particular, the art teaches there is a bias where the TCR CDR3s are predominately involved in peptide binding, and the TCR CDR1 and CDR2 regions are predominately involved in MHC binding, although it should be noted that this bias is not absolute (Manning et al., Immunity, 1998, 8:413-425, specifically page 423, see conclusions).
Further, the prior art provides the skilled artisan with insufficient guidance or direction as to which particular amino acid residues in a given CDR are required for MHC or peptide binding, or which CDR residues are required to bring about the canonical diagonal interaction of the TCR with peptide-bound MHC, see, e.g., Garcia et al., Cell, 2005, 122: 333-336, specially page 333, right column, paragraphs 1-3; page 336, col. bridging paragraph through right column, paragraph 1 and Figure 1. Indeed, one hypothesis in the art is that the CDR1 and 2 interactions with the MHC are dependent on the CDR3 interaction with the peptide bound to the MHC, and, if so, "there may be as many TCR/pMHC orientations as CDR3 sequences” (Garcia et al., page 336, column bridging paragraph).
The TCR interacts with two ligands simultaneously, i.e., the peptide and the MHC, and as described above there is considerable uncertainty in the art about which residues depend on which for these interactions. The instant specification provides no teachings whatsoever and the prior art does not teach as to how the skilled artisan is to go about preparing or envisioning the structural features of the claimed genus of TCRs that can bind to a given peptide:MHC complex starting from as little as a single CDR.
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.
In regards to claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 at1568 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
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 TCRs that encompass the genus 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. Further, in view of Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) and the Office’s February 2018 memo clarifying written description guidance for claims drawn to antibodies, the 2008 Written Description Training Materials are outdated and should not be relied upon as reflecting the current state of law regarding 35 U.S.C. 112. Further, a “newly characterized antigen” test flouts basic legal principles of the written description requirement (Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017)). Adequate written description of a newly characterized antigen alone is not considered adequate written description of a claimed antibody to that newly characterized antigen. Where an antibody binds to an antigen tells one nothing about the structure of any other antibody. Also, see the Board’s decision in Appeal 2017-010877 (claims to “A monoclonal antibody that binds a conformational epitope formed by amino acids 42-66 of SEQ ID NO:1”).
The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.” Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
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 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).
Response to Arguments
In the Reply of 8/26/26, Applicant argues the specification provides written description for claims 336-357.
The amendments to the claims and the arguments found in the Reply of 8/26/26 have been carefully considered, but are not deemed persuasive. Claims 336-357 lack adequate written description for the reasons stated above.
Claim Rejections - 35 USC § 112
Claims 336-357 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for making the six TCRs listed below, does not reasonably provide enablement for making the genus of TCRs encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed.
The instant claims are drawn to a genus of TCRs comprising as little as one recited CDR sequence. This includes a broad genus of TCRs that are not adequately described.
This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The specification discloses:
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 5-7 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 19-21;
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 12-14 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 19-21;
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 90-92 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 97-99;
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 104-106 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 111-113;
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 118-120 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 125-127; and
A TCR comprising a TCR-a polypeptide and a TCR-b polypeptide wherein the TCR-a polypeptide comprises the CDRs set-forth as SEQ ID NOs: 132-134 and the TCR-b polypeptide comprises the CDRs set-forth as SEQ ID NOs: 139-141.
The specification does not adequately describe the broad genus of TCRs encompassed by the claims.
One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to a broad genus of TCRs that are not adequately described, and Applicant has not enabled the claims because undue experimentation would be required to identify and make the genus of TCRs encompassed by the claims.
Further, similar to claims at issue in Amgen Inc. v Sanofi, the instant specification does not enable the full scope of the claims.
In view of the teachings above and the lack of guidance, workable examples and or exemplification in the specification, it would require undue experimentation by one of skill in the art to determine with any predictability, that the method would function as claimed.
Response to Arguments
In the Reply of 8/26/26, Applicant argues the specification provides enablement for claims 336-357.
The amendments to the claims and the arguments found in the Reply of 8/26/26 have been carefully considered, but are not deemed persuasive. Claims 336-357 lack adequate enablement for the reasons stated above.
New Rejections Necessitated by Amendments
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)(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.
Claim(s) 358-359 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Csiszovszki et al (US 10973909 B1; 4/13/21).
Csiszovszki et al treating or preventing an infection in a subject comprising administering the fragment of SARS-COV-2 membrane protein set-forth as SEQ ID NO: 16 to the subject (columns 1-2, in particular). SEQ ID NO: 16 to is a peptide comprising instant SEQ ID NO:24.
Comparison of instant SEQ ID NO:24 (top) and SEQ ID NO:16 (bottom):
PNG
media_image1.png
160
648
media_image1.png
Greyscale
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 SEAN E AEDER whose telephone number is (571)272-8787. The examiner can normally be reached M-F 9am-6pm ET.
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, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SEAN E AEDER/Primary Examiner, Art Unit 1642
Prosecution Insights