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 .
Claims Status
The Amendment filed on 26Feb2026 is acknowledged in which claim(s) 1-92 were canceled, and claim(s) 93-108 are new.
Claim(s) 93-108 is/are currently pending and presented for examination on the merits.
Claim Objections
Claim 94 is objected to because of the following informalities: “ADA2” should be “ADA 2” for consistency with preceding “ADA 1” nomenclature. Appropriate correction is requested.
Claim 97 is objected to because of the following informalities: “further comprising IL2 signal peptide” in line 1 should be “further comprising an IL2 signal peptide”. Appropriate correction is requested.
Claim Interpretation
Claims 100-102 recite(s) “…in an effective amount for treatment of a disease…” in line 2 of claim 100. The instant specification does not define an ‘effective amount’. The broadest reasonable interpretation of the phrase above is considered to be any amount taught in the prior art for the treatment of disease.
Claims 96-97, 103 recite(s) “…operably linked…” in line 1 of claims 96-97, and line2 of claim 103. The instant specification does not define ‘operably linked’. The broadest reasonable interpretation of the phrase above is considered to be any linkage, conjugate, joining, etcetera taught in the prior art.
Claims 101, 107 recite(s) “…wherein the treatment involves immunomodulation of T cells…” in lines 1-2 of claims 101 and 103. The instant specification does not define ‘immunomodulation of T cells’. Kaljas et al. (Cell. Mol. Life Sci. (2017) 74:555–570; hereinafter “Kaljas”) teaches ADA2 immuno-modulates T cells by binding to specific regulatory subsets, and regulates the activation and survival of immune cells [e.g., abstract; pg. 563, col 2, ¶ 2; figs. 3, 7]. Given the above, the broadest reasonable interpretation of the phrase above is considered to include any cell expressing ADA2.
Claim Rejections - 35 USC § 112(b)
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 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.
Claim(s) 96-98, 103 is/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.
Claim(s) 96-97, 103, recite(s) “…ADA is operably linked to one or more of a linker sequence, a human CD3 specific ligand, antibody, scFv, or its derivates…” in line(s) 1-2 of claim 96; and recite(s) “…(ADA) that is operably linked to one or more of a linker sequence, a human CD3 specific ligand, antibody, scFv, or its derivates…” in lines 2-3 of claim 103, rendering the claim(s) indefinite. Specifically, it is unclear if the phrases means that the derivates are of (1) the ADA; (2) a linker; (3) a hCD3 specific ligand; (4) an antibody, (5) a scFv; or (6) something else. For the purposes of compact prosecution, the phrase is considered to mean the derivates are of any of the listed domains (e.g., ADA, linker, hCD3 specific ligand, antibody, scFv). This rejection may be overcome by amending claim(s) 96 and 97 to clearly recite the limitation(s) of the instant invention. Claim(s) 97 can overcome this rejection by amending claim(s) 96 as recited above.
Claim(s) 96-98, 103 is/are indefinite for reciting “or its derivates” as the exact meaning of the word is not known. The term “derivate'' is not one, which has a universally accepted meaning in the art nor is it one which has been adequately described in the specification. The primary deficiency in the use of this phrase is the absence of an ascertainable meaning for said term. The instant specification does not include the term ‘derivate’, but does disclose “…the cell is a T cell, natural killer cell, natural killer T cell, dendritic cell, macrophage, mesenchymal stem cell, and derivatives thereof…” as well as “…ADA derivatives such as ADA-Fc…” [e.g., ¶ 00012, 00040], but the above disclosure is not defined as a closed group limited to the derivatives disclosed in the instant specification. Since it is unclear how (1) the ADA; (2) a linker; (3) a hCD3 specific ligand; (4) an antibody, (5) a scFv; and/or CD26 is/are to be derivatized to yield the class of molecules referred to in the claims, a person of skill in the art cannot describe the metes and bounds of a discrete and identifiable class of molecules to these claims. Claims 96, 98, 103 can overcome this rejection by removing any reference to “derivates”. Claim 97 can overcome this rejection by amending claim 96 as described above.
Claim Rejections - 35 USC § 102
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.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 93-96, 98-108 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2018/0216095 A1 (hereinafter “US095”), as evidenced by BD Biosciences (CD Marker Handbook, 2016; hereinafter “BD”).
Regarding instant claim(s) 93-94, 98, US095 teaches a T cell comprising a chimeric antigen receptor (CAR) and an ADA2 protein [e.g., ¶ 0039, 0682-0685], wherein the cells are autologous (e.g., from the subject) and the subject is human [e.g., ¶ 0682, 0377, 0398]. Human T cells express CD26, as evidenced by BD [e.g., pg. 5, Row 3].
Regarding instant claim(s) 95, US095 further teaches an embodiment wherein ADA2 is secreted [e.g., ¶ 0241].
Regarding instant claim(s) 96, 103-104, US095 further teaches that the ADA2 protein is a conjugate comprising the ADA2 protein linked (e.g., operably linked, see claim interpretation for details) to another polypeptide via a linker [e.g., ¶ 0322, 0325], and that said polypeptide comprises a portion of an antibody (e.g., a portion or ‘derivative’ of an antibody) [e.g., ¶ 0547, 0561]. US095 further teaches the ADA2 protein is recombinant [e.g., ¶ 0262, 0363-0366, 0421, 0426].
Regarding instant claim(s) 99, 105, US095 further teaches a pharmaceutical composition comprising the cell of the invention (e.g., CAR T cell comprising ADA2 protein), and a pharmaceutically acceptable carrier [e.g., ¶ 0063-0064, 0821].
Regarding instant claim(s) 100-102, 106-108, US095 further teaches a method of treating cancer in a subject (e.g., patient) comprising administration of the CAR T cell expressing recombinant ADA2 (e.g., in an amount effective for the treatment of disease; involves immunomodulation of T cells see claim interpretations above for details) [e.g., ¶ 0682-0684, 0747].
Claim Rejections - 35 USC § 103
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 97 is/are rejected under 35 U.S.C. 103 as being unpatentable over by US 2018/0216095 A1 (hereinafter “US095”) as evidenced by BD Biosciences (CD Marker Handbook, 2016; hereinafter “BD”), as applied to claims 93 and 96 above, and further in view of Zhang et al. (J Gene Med 2005; 7: 354–365; hereinafter “Zhang”).
The teachings of US095 as recited above are applied.
Regarding instant claim(s) 97, US095 teaches an ADA2 protein embodiment comprising an N-terminal signal peptide that targets the protein for secretion [e.g., ¶ 0242].
US095 does not expressly teach that the signal peptide is an IL2 signal peptide.
Regarding instant claim(s) 97, Zhang teaches the IL2 signal peptide augments protein secretion both in vitro and in vivo, and is useful for therapeutic secreted proteins [e.g., title, abstract].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to combine the general signal peptide of the secreted ADA2 protein in the CAR T cell expressing ADA2 protein as taught by US095, with the IL2 signal peptide as taught by Zhang, to arrive at an engineered CAR T cell expressing an ADA2 protein operably linked to an antibody and comprising an IL2 signal peptide. A PHOSITA would have been motivated to combine the general signal peptide of the ADA2 protein as taught by US095 with the IL2 signal peptide as taught by Zhang, because US095 teaches the base ADA2 protein structure further comprising a signal peptide, and Zhang teaches an IL2 signal peptide that is useful for therapeutic secreted proteins (e.g., the ADA2 protein of US095) and further that the IL2 signal peptide augments protein secretion in vivo and in vitro. There would have been a reasonable expectation of success for a PHOSITA to combine the general signal peptide of the secreted ADA2 protein in the CAR T cell expressing ADA2 protein as taught by US095, with the IL2 signal peptide as taught by Zhang, because US095 teaches the base structure of the secreted recombinant ADA2 protein comprising a signal peptide and Zhang teaches an IL2 signal peptide that augments protein secretion both in in vitro and in vivo. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
