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 .
DETAILED ACTION
1. The instant Action replaces the Final Rejection Action issued 3/11/2026.
2. Claims 1-27, 29-45, 47-49, 51-62, 64-66, 68-72, 74-76, 78-88 are canceled. Claims 28,
50, 67, 73, 77, 90, 91, 94-96 are amended. New claims 97, 98 are added. Claims 50, 63, 77 are
withdrawn and claims 50, 63 do not contain the proper status identifiers (See MPEP 714).
Newly submitted claim 97 and amended claims 67, 73, 94, 95, 96 are directed to an
invention that is independent or distinct from the invention originally claimed for the following
reasons: new claim 97 and amended claims 67, 73, 94, 95, 96 are directed to nucleic acid (non-
elected Group V as recited in the Restriction Action issued 7/30/2025).
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 Accordingly, claims 67, 73, 94, 95, 96, 97 are withdrawn from consideration as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.
Claims 28, 46, 89-93, 98 are under consideration.
Specification
3. (previous objection, withdrawn) The disclosure was objected to because of
informalities.
Applicant contends: replacement paragraphs have been submitted.
In view of applicant's amendments, the objection is withdrawn.
Claim Objections
4. (previous objection, withdrawn) Claims 91, 94 were objected to because of
informalities.
Applicant contends: the claims have been amended.
In view of applicant's amendments and the withdrawal from consideration of claim 94,
the objection is withdrawn.
Claim Rejections - 35 USC § 112
5. (previous rejection, withdrawn) Claim 95 was 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.
Applicant contends: the claim has been amended.
In view of applicant's amendments and the withdrawal from consideration of claim 95,
the objection is withdrawn.
Claim Rejections - 35 USC § 101
6. (previous rejection, withdrawn) Claims 67, 94 were rejected under 35 U.S.C. 101
and section 33(a) of the America Invents Act as being directed to or encompassing a human
organism.
Applicant contends: the claims have been amended.
In view of applicant's amendments and the withdrawal from consideration of claims 67,
94, the rejection is withdrawn.
7. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement as to inventions III, V, VII as set forth in the Office action mailed on 7/30/2025, is hereby withdrawn and claims 50, 63, 67, 73, 77, 94, 95, 96, 97 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
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.
8. (previous rejection, maintained as to claims 28, 46, 90, 92, 93; withdrawn as to canceled claims 87, 88; new, necessitated by amendment as to claims 50, 63, 67, 73, 77, 94-98) Claims 28, 46, 50, 63, 67, 73, 77, 90, 92-98 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.
See claims 28, 46, 50, 63, 67, 73, 77, 90, 92-98 as submitted 2/2/2026.
Applicant contends: claims 28, 90 have been amended.
Applicant’s arguments are considered and withdrawn as to canceled claims 87, 88, but found unpersuasive as to previous, new and amended claims 28, 46, 50, 63, 67, 73, 77, 90, 92-98.
In view of applicant’s amendments, each of the claims is drawn, inherently or explicitly, to an engineered T-cell Receptor (TCR) comprising a TCR-a polypeptide and a TCR-b polypeptide, wherein the TCR-a polypeptide comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:6, or a sequence at least 90% identical thereto; a CDR2 comprising the amino acid sequence of SEQ ID NO:7, or a sequence at least 90% identical thereto and a CDR3 comprising an amino acid sequence of with at least 80% sequence identity to AVRADRGSTLGRLY (SEQ ID NO:8), or a sequence at least 90% identical thereto and the TCR-b polypeptide comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:12, or a sequence at least 90% identical thereto; a CDR2 comprising the amino acid sequence of SEQ ID NO:13, or a sequence at least 90% identical thereto and a CDR3 comprising an amino acid sequence of with at least 90% sequence identity to ASSVDGGASGEQF (SEQ ID NO:14), or a sequence at least 90% identical thereto. Thus, while requiring the complete CDRs as recited in SEQ ID NOs: 6-8, 12-14, the claims are also drawn to compositions comprising a genus of TCRs comprising an engineered T-cell Receptor (TCR) comprising a TCR-a polypeptide and a TCR-b polypeptide, wherein the TCR-a polypeptide comprises a CDR1 comprising a sequence at least 90% identical to SEQ ID NO: 6; a CDR2 comprising a sequence at least 90% identical to SEQ ID NO: 7, and a CDR3 comprising a sequence at least 90% identical to SEQ ID NO: 8 and the TCR-b polypeptide comprises a CDR1 comprising a sequence at least 90% identical to SEQ ID NO: 12; a CDR2 comprising a sequence at least 90% identical to SEQ ID NO: 13, and a CDR3 comprising a sequence at least 90% identical to SEQ ID NO: 14.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35
U.S.C. 112 written description requirement for a generic claim covering several distinct
inventions:
The written description requirement for a claimed genus may be satisfied through
sufficient description of a representative number of species by actual reduction to
practice..., reduction to drawings..., or by disclosure of relevant, identifying characteristics,
i.e., structure or other physical and/or chemical properties, by functional characteristics
coupled with a known or disclosed correlation between function and structure, or by a
combination of such identifying characteristics, sufficient to show the applicant was in
possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. 'A
"representative number of species" means that the species which are adequately described
are representative of the entire 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.
Thus, when a claim covers a genus of inventions, the specification must provide written
description support for the entire scope of the genus. Support for a genus is generally found
where the applicant has provided a number of examples sufficient so that one in the art would
recognize from the specification the scope of what is being claimed.
In the present case, the application teaches: only a TCR recognizing COL6A3 antigen
(Figures 5, 6; Example 1).
However, a TCR, by its very nature, recognizes and binds to a specific antigen, and requires a structure-function relationship to exist. By reciting wherein the TCR-a polypeptide also comprises a CDR1 comprising a sequence at least 90% identical to SEQ ID NO: 6; a CDR2 comprising a sequence at least 90% identical to SEQ ID NO: 7, and a CDR3 comprising a sequence at least 90% identical to SEQ ID NO: 8 and the TCR-b polypeptide comprises a CDR1 comprising a sequence at least 90% identical to SEQ ID NO: 12; a CDR2 comprising a sequence at least 90% identical to SEQ ID NO: 13, and a CDR3 comprising a sequence at least 90% identical to SEQ ID NO: 14, the scope of the instant claims also reads upon any TCRs with a TCR-a polypeptide and a TCR-b polypeptide comprising a CDR1 comprising a sequence at least 90% identical to SEQ ID NO: 6; a CDR2 comprising a sequence at least 90% identical to SEQ ID NO: 7, and a CDR3 comprising a sequence at least 90% identical to SEQ ID NO: 8 and the TCR-b polypeptide comprises a CDR1 comprising a sequence at least 90% identical to SEQ ID NO: 12; a CDR2 comprising a sequence at least 90% identical to SEQ ID NO: 13, and a CDR3 comprising a sequence at least 90% identical to SEQ ID NO: 14.
It is maintained that it is known in the art that antigen specificity is a complex interaction involving multiple components. Even the most minor differences such as a single mutation can have significant effects on binding ability. The art recognizes that the formation of an intact antigen-binding site generally requires the association of the complete set of entire CDRs which provide the majority of the contact residues for binding to its target epitope. The amino acid sequences and conformations of each of the CDRs are critical in maintaining the antigen binding specificity and affinity. It is expected that all of the CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association is required in order to form functional antigen binding sites.
Rudikoff et al. ("Single amino acid substitution altering antigen-binding specificity," Proc Natl Acad Sci USA 79:1979-1983 (1982))(previously cited): teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Manning et al. (“Alanine Scanning Mutagenesis of an αβ T Cell Receptor: Mapping the Energy of Antigen Recognition,” Immunity Vol. 8: 413-425 (1998))(See PTO-892: Notice of References Cited) teaches: mutations in all 6 of the TCR CDRs leads to unpredictable changes in functions (Fig. 2).
CDRs are variable and unpredictable with respect to binding, so a structure-function
relationship cannot be established based upon sequence homology alone.
Therefore, in light of the knowledge in the art, broad scope of the claims, which reads
upon a genus of TCRs as claimed, and the limited teachings in the specification, there is still a
high level of uncertainty as to which TCRs fall within the scope of the indicated genus and show binding activity.
In view of the fact that the examples provided do not demonstrate possession of the genus encompassing TCRs as claimed, and that the application has identified no structure correlating with constructs with the TCRs' ability to bind, there is insufficient written description support for the indicated genus of TCRs, and therefore for the methods of using them.
For the reasons above, and in view of the uncertainty as to which TCRs would be able to bind using a TCR-a polypeptide and a TCR-b polypeptide, wherein the TCR-a polypeptide comprises a CDR1 comprising a sequence at least 90% identical to SEQ ID NO: 6; a CDR2 comprising a sequence at least 90% identical to SEQ ID NO: 7, and a CDR3 comprising a sequence at least 90% identical to SEQ ID NO: 8 and the TCR-b polypeptide comprises a CDR1 comprising a sequence at least 90% identical to SEQ ID NO: 12; a CDR2 comprising a sequence at least 90% identical to SEQ ID NO: 13, and a CDR3 comprising a sequence at least 90% identical to SEQ ID NO: 14, the application has not provided sufficient written description support for the use of the genus of TCRs identified in claim 28. The application therefore fails to provide adequate support for methods of using this genus of TCRs.
Claim Objections
9. (new objection) Claims 97, 98 are objected to because of the following informalities:
As to claim 97, the claim appears to recite an extra space between "acid" and "of".
As to claim 98, the claim recites "if claim 28", and should recite "of claim 28". Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
10. (new, necessitated by amendment) Claims 50, 63, 67, 73, 77, 94, 95, 96 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
See claims 50, 63, 67, 73, 77, 94, 95, 96 as submitted 2/2/2026.
Amended claim 50 now includes alternative embodiments of nucleic acid encoding the
TCR-a polypeptide or nucleic acid encoding the TCR-b polypeptide, as well as both. Such
recitations are not further limiting of claim 28 on which the claim depends, rather broadening.
Claim 28 on which claim 50 depends requires the presence of both polypeptides. Claim 50 thus
fails to further limit the subject matter of the claim upon which it depends, or fails to include all
the limitations of the claim upon which it depends. Claims 63, 67, 73, 77, 94, 95, 96 depend on claim 50.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper
dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that
the dependent claim(s) complies with the statutory requirements.
Conclusion
11. Claims 89, 91 are objected to for depending on rejected claims.
12. No claims are allowed.
13. 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 M FRANCO G SALVOZA whose telephone number is (571)272-4468. The examiner can normally be reached M-F 8:00 to 5:00.
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, Thomas Visone can be reached at 571-270-0684. 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.
/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672