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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4/17/2026 has been entered.
Applicant’s amendment, filed on 4/17/2026, is acknowledged.
Claims 2, 8-11, and 19-22 are cancelled.
Claims 1, 3-7, and 12-18 are currently pending.
Claims 4 and 12-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
Claims 1, 3, 5-7, 17, and 18 are under examination drawn to the elected species of chimeric antigen receptor comprising a monoclonal anti-CD19 antibody, a CD8 TMD, and the useful cancer to treat of B-ALL.
Terminal Disclaimer
A Terminal Disclaimer for Application 18/263,439 was filed on 4/17/2026. The double patenting rejection with this copending application is withdrawn.
Claim Rejections - 35 USC § 112
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.
Claims 1, 5-7, 17, and 18 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 inventors, at the time the application was filed, had possession of the claimed invention.
The claims are rejected under 35 U.S.C. § 112(a) WD for the same reasons discussed in the Office Action mailed on 1/20/2026. Briefly, the claims encompass a genus of polypeptides with the function of "the intracellular region of a γc chain" without adequate written description support in the instant specification to allow one with ordinary skill in the art to “visualize or recognize” other members of the genus, either by sufficient representative species or through a disclosed structure-function relationship.
Applicant’s remarks, filed on 4/17/2026, have been fully considered, but have been found to be not convincing. Applicant argues (Remarks pg. 3):
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This has been found to be not convincing. Regarding Applicant’s assertation that the “…function of the γc chain intracellular region strictly depends on its membrane-proximal conserved Box 1 motif…for binding JAK3” and citation of Nelson et al. (Mol Cell Biol. 1996 Jan;16(1):309-17. doi: 10.1128/MCB.16.1.309) of the membrane proximal 52 amino acids of the IL-2R γc chain, it is noted that the reference teaches that this amino acid sequence is necessary and sufficient for γc chain function. Figure 2 teaches the sequence of this structure:
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Instant SEQ ID NO: 14 comprises the human WT γc intracellular sequence taught in the figure:
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The cited art teaches that the first 53 residues of instant SEQ ID NO: 16 gives rise to the function of “the intracellular region of a γc chain” and find one other variant of this chain that has one amino acid mutated to preserve function as the γc chain. However, as stated in the Office Action mailed on 1/20/2026, the instant claims encompass all polypeptide species with the recited function, and not only the structures disclosed in the instant specification and taught by the prior art (i.e., SEQ ID NO: 14 or amino acids 1-53 amino acids of SEQ ID NO: 14). This genus includes variants, such as polypeptide structures from other species, with the recited function. For example, NCBI Reference sequence XP_008047055.1 (Uploaded 7/01/2017, ncbi.nlm.nih.gov/protein/XP_008047055.1?report=genbank&log$=prottop&blast_rank=4&RID=AS85FXGB016) teaches a variant of a γc chain that does not comprise instant SEQ ID NO: 14 or amino acids 1-53 of instant SEQ ID NO: 14 (SEQ ID NO: 14 in bottom):
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Neither the instant specification nor the prior art provides sufficient guidance to determine if other polypeptide variants such as this one would retain the recited function of “intracellular region of a γc chain”, which includes activation of JAK3 in response to ligand binding, other than the disclosed structures with the recited function.
Applicant further argues that (Remarks pg. 8): “[t]he written description requirement does not demand such as narrow claim scope when the art recognizes the structural and functional features of the claimed elements.”. However, as discussed supra, the instant specification does not provide sufficient written description support for such as broadly claimed genus of polypeptides with the recited function.
Claims 1, 5-7, 17, and 18 do not meet the requirements of 35 U.S.C. 112(a) for written description.
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.
It is recommended to amend claim 1 to recite specific polypeptide structures, defined by their amino acid sequences, disclosed in the specification with the function of “the intracellular region of a γc chain” to overcome this rejection.
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.
Claims 1, 3, 5, 7, 17, and 18 are rejected under 35 U.S.C. 102(a)(1)/(2) as being anticipated by Yang et al. (WO2019242339, in Office Action mailed 1/20/2026).
Claim 1 claims a CAR comprising an antigen binding region, a TM domain, a 4-1BB costimulatory domain, a CD3ζ ICD, and a γc chain intracellular region, wherein the costimulatory domain, ICD, and γc chain are arranged in order of nearest to furthest of the cell membrane.
Yang et al. teaches (Abstract): “a chimeric antigen receptor having a structure of scFv(X)-(Y)CD3zeta-MN”. Yang et al. additionally teaches that Y is a costimulatory region (Abstract). Yang et al. further teaches (pg. 5, Step 2): “M is the intracellular region of the gamma chain family cytokine receptor selected from IL2Ra, IL2Rb, IL4Ra, IL7Ra, IL9Ra, IL15Ra, IL21Ra ; N is the intracellular region of IL2Rg”. Also see Figure 1:
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Yang et al. teaches a CAR comprising an scFv, a 4-1BB costimulatory domain, a CD3ζ ICD, and a γc chain, wherein the costimulatory domain, ICD, and γc chain are arranged in order of nearest to furthest of the cell membrane (see arrangement is Fig. 1). Yang et al. further teaches specific CAR embodiments that have a CD8 TM domain that is 100% identical to instant SEQ ID NO: 4 (Yang et al. SEQ ID NO: 1):
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Therefore, Yang et al. anticipates instant claims 1, 5, and 7.
Regarding instant claim 3, Yang et al. additionally teaches an CARs comprising the IL2Rg sequence of SEQ ID NO: 7 (Example 4-20), which is 100% identical to instant SEQ ID NO: 16, anticipating the claim limitations:
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Regarding claim 17, Yang et al. teaches compositions (i.e., “pharmaceutical compositions”) comprising the CAR and cell supernatant (i.e., a “pharmaceutically acceptable excipient”; Yang et al. Example 4-20), anticipating the claim limitations.
Claim 18 is included because a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, Yang et al. teaches the same structure encompassed by the instant claims, and therefore is capable of performing the intended use recited in instant claim 18, meeting the claim limitations.
The reference teachings anticipate the instantly claimed invention.
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.
Claims 1, 5-7, 17, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Rezvani et al. (WO2018195339, in Office Action mailed on 1/20/2026).
The claims are rejected for the same reasons discussed in the Office Action mailed on 1/26/2026. Briefly, Rezvani et al. teaches CARs comprising an anti-CD19 scFv, a CD8 TM domain, a CD3ζ ICD, a 4-1BB costimulatory domain, and a γc intracellular domain, and one with ordinary skill in the art would be motivated to arrange the domains in the order from CD3ζ, 4-1BB, and γc intracellular domain from closest to furthest of the plasma membrane.
Applicant argues unexpected results of the instant claimed chimeric antigen receptors:
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This has been found to be not convincing.
The specification further discloses (Example 4, ¶[00101]): “[t]he ye chain intracellular region (SEQ ID NO: 15) was inserted between the 4-lBB costimulatory domain and the CD3 ζ primary signaling domain of the bbz-CAR plasmid to obtain the bbgzCAR plasmid, which differs from the bbzg-CAR plasmid only in that the position of the yc chain intracellular region is different. The bbgz-CAR T cell was prepared according to the method of Example 1.”
The disclosure of unexpected results based on the positioning of the γc chain structure of SEQ ID NO: 15. SEQ ID NO: 15 is the nucleic acid sequence that encodes instant SEQ ID NO: 16 (translation of SEQ ID NO: 15 on top):
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Therefore, it is the Examiner’s positions that:
(i) the showing of unexpected results is not commensurate in scope with the invention as claimed. The claims are directed to a genus of CARs comprising any polypeptide structure with the function of “intracellular regions of a γc” (claim 1). The claims do not recite the specific structure of γc chain that led to unexpected results due to its positioning. Tere is no showing that other embodiments falling within the claims will behave in a similar unexpected manner.
(ii) The results of unexpected results must be due to the claimed features, not to unclaimed features. The instant claims does not recite that the γc intracellular region that were found to increase cytotoxicity due to its positioning in a CAR (i.e., the structure in Example 4).
Additionally, the instant claims use the open language (instant claim 1): “…chimeric antigen receptor comprising…” which is open language and does not exclude additional structures such as an additional subunit.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary
Claims 1, 3, 5-7, 17, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (WO2019242339, in Office Action mailed 1/20/2026, supra).
The claims are rejected for the same reasons discussed in the Office Action mailed on 1/26/2026.
Applicant’s arguments, filed on 4/17/2026, have been fully considered, but have been found to be not convincing.
Applicant argues unexpected results of the instant claimed chimeric antigen receptors (see supra), and that Yang et al. teaches CARs that contain additional subunits that the instant invention does not contain.
This has been found to be not convincing.
The instant claims use the open language (instant claim 1): “…chimeric antigen receptor comprising…” which is open language and does not exclude additional structures such as an additional subunit(s) taught by Yang et al.
Regarding the demonstration of unexpected results, Applicant’s reliance on unexpected results do not overcome clear and convincing evidence of obviousness. Also see Richardson-Vicks Inc. v. Upjohn Co., 44 USPQ2d 1181 (CAFC 1997). In Paper No. 8, applicant argued that the reference is silent about all of the claimed properties and that the reference is not enabling, but had not provided any objective evidence to support these assertions. Whether the rejection is based on "inherence" under 35 U.S.C. § 102 or prima facie obviousness under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. Examiner properly shifted burden to applicant to establish, through objective evidence, that hybridoma and monoclonal antibody of invention differ in unobvious manner from those of the prior art references. Ex parte Phillips, 28 USPQ2d 1302 (BPAI 1993).
Here, applicant has not provided any objective evidence to support the difference between the prior art and instant chimeric antigen receptors comprising a 4-1BB costimulatory domain, a CD3ζ ICD, and a γc intracellular region in the arrangement from nearest to furthest from the cell membrane. The record does not contain sufficient objective evidence that the referenced CARs differ in any significant manner from that claimed.
The prior art teaches the same benefited of unexpected results. Applicant’s reliance on unexpected results do not overcome clear and convincing evidence of obviousness. Also see Richardson-Vicks Inc. v. Upjohn Co., 44 USPQ2d 1181 (CAFC 1997). The issue is whether the properties differ to such an extent that the difference is really unexpected. There is nothing unextend in Applicants’ results because the reference teachings arrived to the same unexpected results of chimeric antigen receptors greater cytotoxic effect (Example 4, Fig. 7). Accordingly, the unexpected results were suggested by Yang et al. which teach chimeric antigen receptors comprising a 4-1BB costimulatory domain, a CD3ζ ICD, and a γc intracellular region arranged from nearest to furthest from the cell. By the same reasoning, these CARs would confer a greater cytotoxic effect than other intracellular arrangements of domains (Example 4, Fig. 7). Therefore, one of ordinary skill in the art at the time of the invention was made aware of the teachings of Yang et al. would use these CARs with the greater cytotoxic effect. When considering obviousness of a combination of known elements, the operative question is thus "whether the improvement is more than the predictable use of prior art elements according to their established functions." KSR at 418. In the instant case, the inventors merely used routine research methods to prove what was already believed to be the case.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary
Conclusion
No claim is allowed.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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