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 election without traverse of Group I (drawn to an engineered protein) and the species of CD3G extracellular domain, a CD3G transmembrane domain, a CD28 domain, and a CD40 domain, a cognate TCR antigen ligand for a TCR incorporated antigen agnostic receptor (TIAAR) in the Response filed on July 22, 2026 is acknowledged.
Claims 6-11, 18, 20, 22, and 32-45 have been canceled.
Claims 1-5, 12-17, 19, 21, and 23-31 are pending.
Claims 14-16, 24, 26, and 27 have been withdrawn under 37 CFR 1.142(b) as being drawn to nonelected inventions or species.
Claims 1-5, 12, 13, 17, 19, 21, 23, 25, and 28-31 are currently under consideration as they read on the elected invention.
3. The drawings are objected to because Figure 1A is blurry. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
4. The instant application appears to be in sequence compliance for patent applications containing nucleotide sequence and/or amino acid sequence disclosures, except for the following:
It does not appear that all of the sequences disclosed in the specification as filed are provided with the appropriate SEQ ID NOS. in compliance with the Sequence rules as set forth in 37 CFR 1.821(d).
For example, the amino acid sequences disclosed in [0041] and [0043] in pages 12-13 of the specification as-filed are not accompanied by SEQ ID NOs. Applicant is reminded of the Sequence Rules which require a submission for all sequences of 10 or more nucleotides or 4 or more amino acids (see 37 CFR 1.1821-1.1825) and is also requested to carefully review the submitted specification for any and all sequences which require compliance with the rules.
5. 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.
6. Claims 17 and 23 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A) Claim 17 recites the limitation "the chimeric protein" in 2. There is insufficient antecedent basis for this limitation in the claim.
B) Claim 23 is indefinite in the recitation of, e.g. CD3G_CD3G_CD28CD40 because the metes and bounds of the recitation is ambiguous. It is not clear if the proteins are linked in view of the use of “_” between the two CD3G and CD3G and CD28 and the use of “CD28CD40”. Further, it is not clear if recited CD3G_CD3G means two CD3Gs connected together or two partial CD3G, e.g. transmembrane domain of CD3G connects to the intracellular domain of CD3G.
7. 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. Claims 1-5, 12, 13, 17, 19, 21, 23, 25, 28-31 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.
The instant claims are drawn to an engineered protein comprising a clustering domain comprising a TCR clustering domain comprising a protein component of a TCR complex or a portion thereof and a signaling domain comprising a CD40 signaling domain or signaling fragment thereof, wherein the clustering domain is capable of oligomerization when the signaling domain is activated. Dependent claim 21 further recite that the engineered protein comprises a T cell receptor integrated antigen agnostic receptor (TIAAR). Dependent claim 23 further recite CD3G_CD3G_CD28CD40 or CD3G_CD3G_CD3G (ICD)_CD28CD40 (the elected species).
The specification discloses that the TCR clustering domain may comprises one or more protein typically found in TCR complex including CD3D, CD3E, CD3G, or CD3Z or a portion thereof (e.g. see [0032] in page 8 of the specification as-filed). Regarding TIAAR, the specification discloses examples of component from CD3 receptors such as CD3G_CD3G_CD28CD40 or CD3G_CD3G_CD3G (ICD)_CD28CD40 (e.g. see Table 2 in page 44-45 of the specification as-filed. It is not clear if the CD3G repeats in these structures are the full length CD3G or specific part of the CD3G, e.g. extracellular domain, transmembrane domain, or intracellular domain.
The specification further discloses T cells with all TCR components except that the ζ intracellular domain was replaced with CD28CD40 (e.g. see Figure 1A) or copy below for convenience:
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There is insufficient written description in the specification as-filed of the engineered protein comprising a TCR clustering domain and a CD40 signaling domain as recited in the instant claims.
The claims recite a genus engineered protein comprising a clustering domain and a signaling domain comprising CD40 signaling domain or signaling fragment thereof as part of the invention without providing a physical structure or testable functional activity for the TCR clustering domain and the CD40 signaling domain.
The genus of the engineered proteins is therefore extremely large. Applicant has disclosed specific engineered proteins having specific components of for the extracellular domain, transmembrane domain, and intracellular domains (e.g. see pages 46-49 of the specification as-filed). Thus Applicant has disclosed only a limited species of the engineered proteins, namely those with specific components in specific orientations. The claimed TCR clustering domain and CD40 signaling domain and TIAAR lack a common structure essential for their function and the claims do not require any particular structure basis or testable functions be shared by the instant engineered proteins.
For example, Call et al. (Cell 2002, December 27, 111(7):967-979) teach that a striking feature of TCR is the presence of nine highly conserved potentially charged residues in the transmembrane helices; and one basic and two acidic transmembrane residues are required for the assembly of each of the three signaling dimers with the TCR (e.g. see Abstract). Thus, it appears that the biological TCR cluster domains are located mainly in transmembrane regions of TCR.
It does not appear based upon the limited disclosure of specific TCR clustering domains oriented in specific order with respect to the CD40 signaling domain and in assembly with TCR that Applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the limited number of species disclosed and the extensive variation permitted within the genus of a clustering domain comprising a T-cell receptor clustering domain comprising a protein component of a TCR complex or portion thereof.
The engineered protein comprising a clustering domain comprising a TCR clustering domain comprising a protein component of a TCR complex or a portion thereof and a signaling domain comprising CD40 signaling domain or signaling fragment thereof encompass distinct and diverse structures and do not encompass common structural elements essential to the functions as recited, e.g. capable of oligomerization by self-assembly to form a homodimer or complex formation with a receptor.
“Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Regents of the University of California v. Eli Lilly and Co. 43 USPQ2d 1398 (Fed. Cir. 1997).
The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter of the claim. Id. 43 USPQ2d at 1406.
In the absence of disclosure of relevant, identifying characteristics of the engineered protein, there is insufficient written disclosure under 35 U.S.C. 112, first paragraph.
9. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
10. 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.
11. Claims 1-5, 12, 13, 17, 19, 21, 25, and 28-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by June et al. (WO 2015/112626, reference on IDS) as evidenced by the disclosure of TCR incorporated antigen agnostic receptors (TIAARs) in pages 42-43 of the instant specification and as further evidenced by the disclosure of “clustering domain” in page 3 of the instant specification as-filed.
June et al. teach a CAR comprising a protein from T-cell receptor and a signaling domain from CD40 (e.g. see [0022]-[0023]). June et al. further teach that the CAR comprises an extracellular antigen binding domain, a transmembrane domain from CD3α, β, or ζ, an intracellular domain CD28, costimulatory signaling domain from CD40 (e.g. see [00157]-[00162]).
June et al. teach the CAR also comprises a signaling peptide, a target-specific binding element such as antigen-binding domain (e.g. see [00177]). June et al. teach the trans membrane domain capable of forming dimers (e.g. see [00181]).
As evidenced by pages 42-43 of the instant specification, TIAARs can be CD3 receptors. As further evidenced by page 3 of the instant specification as-filed, “a clustering domain” can be one or more of the proteins typically found in TCR complex including CD3G, CD3E, CD3Z, CD3-eta.
Given that the prior art CAR has the same structure as the instantly claimed engineered protein, namely having a clustering domain and a signaling domain comprising CD40 signaling domain, the prior art CAR would inherently have the same functions including self-assembly such as formation of a homodimer, complex formation with a receptor including ligand binding (in instant claims 2-5), oligomerizes when bound by a ligand (in instant claim 12), co-stimulates a T cell when an endogenous T cell receptor engages its cognate antigen (in instant claim 17).
Therefore, the reference teachings anticipate the instant invention.
12. No claim is allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 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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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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