DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 08/16/2023, is acknowledged.
3. Claims 1-13 and 15-24, 27-35, 37-40 are pending.
4. Applicant’s election with traverse of Group II , claims 19-24, 27-28, 32-33, directed to a nucleic acid encoding a TRC has antigenic specificity for a CD22, vectors, method of producing host cells, and a method of producing a TCR using a host cell, and SEQ ID NO: 1-6, 10, 11 and SEQ ID NO: 20, wherein X11 is Leu, X114 is Ile and X115 is Val and SEQ ID NO: 21, wherein X57 is Cys, filed on 04/15/2026, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
5. Claims 1-13, 15-18, 29-31, 34-35 and 37-40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
6. Claims 19-24, 27-28, 32-33 are under examination as they read on a nucleic acid encoding a TRC has antigenic specificity for a CD22, vectors, method of producing host cells, and a method of producing a TCR using a host cell, and SEQ ID NO: 1-6, 10 (alpha chain), 11 (beta chain) and SEQ ID NO: 20, wherein X11 is Leu, X114 is Ile and X115 is Val and SEQ ID NO: 21, wherein X57 is Cys.
7. Applicant’s IDS, filed 03/20/2024, is acknowledged.
8. Claim 19 is objected to because it depends from withdrawn claim 1 and it should be written in an independent format. A claim that refers back to a withdrawn base claim must be rewritten entirely in independent form.
9. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
10. Claims 19-24, 27-28, 32-33 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.
Claim 19 encompasses a broad genus of nucleotide sequences encoding the TCR comprising less than the required 6 CDRs, three CDRs from the alpha chain and three CDRs from the beta chain presented on a genus of HLA Class I molecules.
Claim 20 encompasses the combination of first the alpha and then beta chains or first beta and then alpha chains from 5` to 3`.
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of binding CD22. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that 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 genus.
The specification on [0042] discloses that the HLA Class I molecule is an HLA-A molecule. The HLA-A molecule is a heterodimer of an α chain and β2 microglobulin. The HLA-A α chain may be encoded by an HLA-A gene. β2 microglobulin binds non-covalently to the alpha chain to build the HLA-A complex. The HLA-A molecule may be any HLA-A molecule. In aspects of the invention, the HLA Class I molecule is an HLA-A02 molecule. The HLA-A02 molecule may be any HLA-A02 molecule. Examples of HLA-A02 molecules may include, but are not limited to, those expressed by the HLA-A*02:01, HLA-A*02:02, HLA-A*02:03, HLA-A*02:05, HLA-A*02:06, HLA-A*02:07, and HLA-A*02:11 alleles. Preferably, the HLA-A02 molecule is expressed by the HLA-A*02:01 allele.
[0015] FIG. 3 presents flow cytometry plots showing enrichment of HLA-A*02:01 CD22 p228-236 tetramer-binding CD8+ T cells after repeated stimulation with A2+ DC/K562A2 loaded with CD22 p228-236, also see [0146], [0151].
The specification at [0049] discloses the TCR comprises a first polypeptide chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 1 (CDR1 of a chain), a CDR2 comprising the amino acid sequence of SEQ ID NO: 2 (CDR2 of a chain), and a CDR3 comprising the amino acid sequence of SEQ ID NO: 3 (CDR3 of a chain), and a second polypeptide chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 4 (CDR1 of b chain), a CDR2 comprising the amino acid sequence of SEQ ID NO: 5 (CDR2 of b chain), and a CDR3 comprising the amino acid sequence of SEQ ID NO: 6 (CDR3 of b chain).
Example demonstrates the method of identification of a TCR having antigenic specificity for CD22 p228-236 using allogeneic stimulation, in accordance with aspects of the invention.
Table 7 of the specification provides TCR variable regions had sequences with/signal peptide comprising alpha chain with/out signal peptide of SEQ ID NO: 7 and 10 and beta chain with/out signal peptide of SEQ ID NO: 9 and 11.
To allow cloning of the CD22-specific TCR expression cassette into the MSGV1 vector 5′NcoI site, the second amino acid in the TCRVP chain (the second amino acid within the N-terminal signal peptide) was changed to an alanine (A). The expression cassette had the following configuration: 5′NcoI-VDJβ-mCβ-Furin/SGSG/P2A-VJα-mCα-SalI3′. The nucleotide sequences of each TCR were codon optimized for human tissue expression. See FIG. 5. This example describes a synthesis of bicistronic vector in 5′TCRβ to TCRα 3′ orientation, but the order of TCRβ to TCRα can be reversed. The vector insert sequences were codon optimized for an expression in human tissues [0160].
As has been long known by the skilled artisan, antibodies and TCRs have structural and
functional similarities. For example, both molecules are heterodimers based on the characteristic
immunoglobulin fold, genes encoding both molecules are constructed via V(D)J recombination
of germline encoded nucleic acids, both molecules rely on accessory molecules to promote signal
transduction upon ligand binding.
By analogy to antibodies, several recent court decisions speak to the notion that claiming a
molecule with unknowable structural heterogeneity solely by reciting its function is not sufficient
to establish possession of a genus so claimed.
Rather, “[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 the species which are 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.
See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300,
111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus
of antibodies were not supported by a disclosure that "only describe[d] one type of
structurally similar antibodies" that "are not representative of the full variety or scope of the
genus.").
Likewise, the Federal Circuit has cautioned that, for claims reciting a genus of antibodies with
particular functional properties (e.g., high affinity, neutralization activity, competing with
a reference antibody for binding, binding to a certain epitope), “[claiming antibodies with
specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in
a claim that does not meet written description even if the human TNF-α protein is disclosed
because antibodies with those properties have not been adequately described." Centocor Ortho
Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
Along these same lines, as more recent Federal Circuit decision, Amgen v. Sanofi, 872 F.3d
1367 (Fed. Cir. 2017), describes how when an antibody is claimed, 35 U.S.C. § 112(a) requires
adequate written description of the antibody itself not just a description of the sequence to
which the antibody binds. Amgen, 872 F.3d at 1378-79.
The specification provides one anti-TCR having antigenic specificity for CD22 p228-236 using allogeneic stimulation, which were not random combinations of alpha chain and beta chain i.e., it had specific alpha chain (SEQ ID NO: 7 and 10) paired with specific beta chain (SEQ ID NO: 9 and 11, respectively). No other α/β chain was provided that mix the alpha chain CDR1-3 of SEQ ID NO: 1-3 or beta chain CDR1-3 of SEQ ID NO: 4-6 with other β/α chain form different clone. The specification only CD22 binding human TCR beta chain-linker-alpha chain, SEQ ID 28. The instant application encompasses (but does not exemplify) TCR having antigenic specificity for a CD22 amino acid sequence presented by a human leukocyte antigen (HLA) Class I molecule, white the specification shows that CD22 p228-236 is predicted to bind to the HLA-A*02:01 molecule with high affinity (Table 5) [0146].
Neither the specification, nor the prior art provides any examples to support the premise of alpha chain CDRs or beta chain CDRs would result in TCR having antigen binding specificity. The prior art does not support a definition of an TCR structure by alpha or beta chain CDR1-3 sequence would result in functional TCR having antigenic specificity for a CD22 amino acid sequence. The specification provides no direction or guidance regarding how to produce TCR as broadly defined by the claims. Undue experimentation would be required to produce the invention commensurate with the scope of the claims from the written disclosure alone. Further, the specification does not teach that a functional TCR can be obtained by either the alpha or beta CDR regions comprising the less than all the 6 CDRs sequences.
Claim 32 recite a method of producing a TCR polypeptide or protein comprising culturing the host cell comprising the nucleic acid accordingly to claim 19 however, claim 19 encompasses the alpha chain, the beta chain or both. A host cell that comprises either beta or alpha chain would not result in production of TCR polypeptide/protein.
Claim 28 dis directed to host cell comprising the nucleic acid of claim 19. It is not that the claimed host cell in claim 28 does require the presence of a promoter or enhancer (i.e., vector) to express the nucleic acid of the TCR having antigenic specificity for a CD22. It is suggested that claim 28 depends from claim 23 or 24.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “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.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
11. No claim is allowed.
12. The art made of record and not relied upon is considered pertinent to applicant's disclosure:
Nguyen et al. CD22 TCR- engineered T cells exert antileukemia cytotoxicity without causing inflammatory responses. Nguyen et al., Sci. Adv. 11, eadq4297 (2025) 9 April 2025.
Nguyen et al used an approach of allogeneic stimulation to enrich T cells expressing TCRs specific to an HLA- A*02:01–restricted epitope of CD22 (CD22p228–236, amino acid FLSNDTVQL) (Fig. 1A). CD22p228–236 is a peptide estimated to bind to HLA- A*02:01 at high affinity based on a prediction algorithm (IEDB, www.iedb.org) (40) and reported to be a naturally processed and presented epitope of B cells (see page 2, under results).
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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June 2, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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