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 .
1. The Amendment filed June 10, 2026 in response to Office Action of March 10, 2026, is acknowledged and has been entered. Claims 1-2, 5-9, 11-12, 14-19, and 24 are now pending. Claims 3-4, 10, and 13 are cancelled. Claims 1-2, 5-6, 9, 11-12, and 24 are amended.
Claims 1-2, 5-9, 11-12, 14-19 and 24 are currently being examined.
Withdrawn Rejections
2. Claims 12-19 and 24 were rejected under 35 U.S.C. 112(a) for enablement. In response Applicant has amended claims 12 and 24 in accordance with examiner’s suggestion to delete the term “prevention”. Thus, the rejection is withdrawn.
3. Claim 6 was rejected under 35 U.S.C. 112(b) for indefiniteness. Applicant has amended the claim to overcome the rejection. Thus, the rejection is withdrawn.
4. Claim 13 was rejected under 35 U.S.C. 112(d) as being in improper dependent form. In response, Applicant has cancelled claim. Thus, the rejection is withdrawn.
5. Claims 1-3, 5-8, and 24 were rejected under 35 U.S.C. 101 as being directed to a human organism. Applicant has amended claim 1, 2, 5, 9, and 12 to recite an “isolated” cell. Thus, the rejection is withdrawn.
6. Claims 1-3, 5-7, and 9-11 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jamali (Front Immunol. 2020, 11:2028), as evidenced by Mokhtari (Oncotarget, 2017, 8(23):38022-38043). Applicant has amended claims to recite A T cell expressing a CAR targeting CD25 and a CXCL12 receptor, which is not disclosed in Jamali. Thus, the rejection is withdrawn.
7. Claims 1-5, 7-8, and 24 were rejected under 35 U.S.C. 103 as unpatentable over Li (WO 2020/135083) in view of Arai (Biol. Blood Marrow Transplant, 2018, 24(S311):447). Claims 12-16 and 18-19 were rejected under 35 U.S.C. 103 as being unpatentable over Jamali in view of Zhang (Blood Advances, 2020, 4(10):2325-2338). Claim 17 was rejected under 35 U.S.C. 103 as being unpatentable over Jamali in view of Zhang as applied to claims 12-16 and in further view of Vatsan (Journal for Immunotherapy of Cancer, 2013 1:5). Applicant has amended claims to recite a T cell expressing a CD25 CAR and a CXCL12 receptor protein and a method for treatment using the CD25 CAR T cell expressing CXCL12 receptor, which overcomes the references cited in the above rejections. Thus, the rejections are withdrawn.
Maintained Rejections
(Updated in response to amendments)
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.
8. Claims 1-2, 5-9, 11-12, 14-19, and 24 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. This is a WRITTEN DESCRIPTION rejection
The claims are drawn to a T cell co-expressing a chimeric antigen receptor (CAR) protein that targets CD25 and a CXCL12 receptor protein on the cell membrane.
Dependent claims 9 and 11 further recite the T cell of claim 1 introducing a first polynucleotide encoding a CAR protein and a second polynucleotide encoding a CXCL12 receptor protein into a cell, wherein the CAR targets CD25.
Dependent claims 12, 14-19, and 24 require the T cell co-expressing a CAR protein targeting CD25 and a CXCL12 receptor protein to treat relapse of a neoplastic disease.
Thus, the claims encompass a vast genus of T cells co-expressing a CAR and CXCL12 receptor protein, where the CAR is defined by the function of binding CD25 and no amino acid sequence structure.
The instant specification discloses two separate constructs that were made: a CXCR4-expressing CD25 CAR-T cell (See Example 1 and 2 pg. 34-36 [0107]-[0114]) and a CXCR4-expressing CD19 CAR-T cell (See Examples 3 and 4, pg. 36-37 [0115]-[0120]). However, the specification does not disclose the sequences of the CARs that function to bind CD19 or CD25.
The instant specification further discloses the anti-IL2RA/CD25 protein single chain variable fragment (scFv) and intracellular CD3z and CD137 (4-1BB) signaling domains for preparing the CD25 CAR protein were designed according to Figure 2A and Michael C. Milone, et al., 2009, Mol. Therapy, 17(8): 1453-64, which was incorporated by reference (See Reference Example 2, pg. 32, [0098]). A review of Milone 2009 reveals a CAR construct that binds to CD19 and not to CD25. Further, the sequences of the CAR binding to CD25 are essential material for making and using the cells as claimed. MPEP 608.01(p) states: “For the written description requirement, an applicant’s specification must reasonably convey to those skilled in the art that the applicant was in possession of the claimed invention as of the date of invention”. MPEP 608.01(p) further defines the conditions for proper incorporation by reference under 37 CFR 1.57:
37 CFR 1.57 states (bold emphasis added):
(c)
“Essential material” may be incorporated by reference, but only by way of an
incorporation by reference to a U.S. patent or U.S. patent application
publication, which patent or patent application publication does not itself
incorporate such essential material by reference. “Essential material” is material
that is necessary to:
(1) Provide a written description of the claimed 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 is most nearly connected, to make and use the same, and set forth the
best mode contemplated by the inventor of carrying out the invention as
required by the first paragraph of 35 U.S.C. 112;
(2) Describe the claimed invention in terms that particularly point out and
distinctly claim the invention as required by the second paragraph of 35
U.S.C. 112; or
(3) Describe the structure, material, or acts that correspond to a claimed means
or step for performing a specified function as required by the sixth paragraph of
35 U.S.C. 112.
Thus, the incorporation by reference of non-patent literature to describe essential material is improper.
Thus, the instant specification discloses making two CXCR4-expressing CAR-T cell constructs, which bind to CD25 and CD19, but does not disclose their sequences. The specification states that it discloses the structure of the anti-CD25 binding portion of the CD25 CAR protein, but by an improper incorporation by reference, and to a reference that appears to describe a CD19 CAR.
The specification fails to disclose a single exemplary sequence structure of an anti-CD25 binding region for a CD25 CAR protein.
To provide adequate written description and evidence of possession of the claimed CAR T cell genus, the instant specification can structurally describe representative CARs that function to bind CD25 or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
In this case, the only factor present in the claims is a recitation of a CAR T cell function of targeting CD25 and the co-expression of a CXCL12 receptor and no amino acid structure. The instant specification fails to describe structural feature common to the members of the CAR T cell genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative CAR T cell variant sequences that function as claimed. Other than the CXCR4 CAR constructs described above, the specification fails to provide the CAR structural features coupled to the claimed functional sequences. Therefore, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of CAR T cells required to make and use the cells as claimed.
Although Applicants may argue that it is possible to screen for CAR T cells that bind CD25 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘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.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future CAR T cells yet to be discovered that may function as claimed. The CD25 antigen provides no information about the structure of a CAR T cell that binds them.
Given the lack of representative examples to support the full scope of the claimed CAR T cells targeting CD25, and lack of proper sequence disclosure, the present claims lack written description. Thus, the specification does not provide an adequate written description of CAR T cells that bind CD25 and express CXCL12 receptor proteins that are required to practice the claimed invention.
Response to Arguments
9. Applicant points to the Ishikawa declaration filed under 37 CFR 1.132 and argues that the specification provides detailed disclosure of the CD25 CAR construct through the disclosure of the anti-L25RA/CD25 protein scFv and intracellular CD3ζ and CD137 (4-1BB) signaling domains disclosed in Figure 2A and paragraphs [0044]-[0045], [0098].
Applicant argues that the written description does not require a disclosure of amino acid sequence by reciting MPEP 2163 (quoting In re Herschler, 591 F.2d 693, 700-01 (CCPA 1979) and citing further support by Teva Pharmaceuticals International GMBH v. Eli Lilly & Company, No. 24-1094 (Fed. Cir. Apr. 16, 2026). Specifically, Applicant argues that the specific structural disclosure is not required because the specific components of the CAR- the CAR design itself, the anti-CD25 scFv, and the CXCR4 sequence are well known in the art and is not the claimed invention. Therefore, the disclosure of the specific amino acid structure of the anti-CD25 scFv portion of the CAR genus is not required.
10. Applicant's arguments filed June 10, 2026 have been fully considered but they are not persuasive.
In Applicant’s response on page 2, they quote MPEP 2163 as supporting their position that the sequences do not need to be disclosed since they are well known in the art. However, Applicant misses the precise context of which this instruction is given, “The Federal Circuit has consistently held that the written description requirement does not demand disclosure of specific sequences or structures when the claimed genus is well known in the art and is not itself the invention. In re Herschler, 591 F.2d 693, 700-01 (CCPA 1979) ("use of known chemical compounds in a manner auxiliary to the invention must have a corresponding written description only so specific as to lead one having ordinary skill in the art to that class of compounds"); MPEP § 2163 ("the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function").
The quote makes clear that a claimed genus well known in the art does not need to be fully disclosed when the genus is not itself the invention. In the present case, especially in light of the new amendments, the T cell co-expressing a CAR protein targeting CD25 is itself the invention. As the quote from In re Herschler provides, “a use of a known chemical compound auxiliary to the invention,” the CAR protein targeting CD25 as recited in independent claims 1 and 12 is not auxiliary to the invention, it is the invention itself.
Further, as instructed above, the written description may be satisfied through disclosure of function and minimal structure when there is well established correlation between structure and function. As maintained in the argument above from the previous office action, the specification fails to provide an adequate description of any amino acid structure correlated to the function of a T cell expressing a CAR protein targeting CD25 and a CXCL12 receptor protein in the cell membrane.
In this case the genus of a T cell co-expressing a CAR protein targeting CD25 and a CXCL12 receptor protein on the cell membrane requires a well-established correlation of structure to function. This structure and function applies to the whole invention, not just the components of it analyzed independently. Applicant argues on page 7 citing the submitted Declaration:
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However, the individual components of the T cell co-expressing a CAR protein targeting CD25 and a CXCL12 receptor do not function separately but together. Thus, the structure and function of the genus must be correlated together as one invention not as separate components.
Further, Applicant asserts that the claimed subject matter of the invention is not the anti-CD25 scFv itself but the therapeutic use of a CXCR4-expressing CD25 CAR T cell. (Pg. 7, lines 23-24) However, Claim 1 is drawn to a T cell co-expressing a CAR protein target CD25 and a CXCL12 receptor protein, not a therapeutic use of the construct.
Regarding claims 12 and 14-19 reciting methods for treatment of relapse of neoplastic disease in a subject by administering an isolated T cell co-expressing the CAR targeting CD25 and a CXCL12 receptor protein, the CAR targeting CD25 is a critical element in the T cell performing the claimed functions of treating relapse of neoplastic disease in conjunction with the CXCL12 receptor protein. Without adequate written description provided for the CD25 CAR, one of ordinary skill in the art cannot recognize which CAR sequences in the vast genus claimed would function as claimed, and one cannot immediately recognize members of the claimed genus required to practice the claimed method.
Further, Applicant speaking about the design of the construct on page 11, “This is not a generic combination of known elements; rather, it is a precise immunotherapy construct for targeting CD25-expressing hematologic malignancies such as AML-a disease for which CAR-T cell therapy has historically shown "dismal clinical outcomes." Meaning the targeting of CD25 is a part of the therapeutic approach of the invention, making it the invention itself.
Applicant further asserts the CD25 was chosen for the construct, without a reasonable expectation of success stating on page 14, “CD25 is a fundamentally different target antigen from CD19, associated with different diseases (AML versus B-ALL) and expressed on different cell populations. As the present inventors themselves demonstrated, CD25 CAR-T cells alone were unable to eradicate AML cells from the bone marrow-a result that was itself contrary to expectations.” (emphasis by Applicant). Indicating that the CD25 targeting is an essential part of the therapeutic invention claimed.
Applicant cites the recent court case, Teva v. Lilly as supporting their position. However, Teva applies to a genus of humanized anti-CGRP antagonist antibodies that are well known in the art. In the instant case, the genus is not separately a second generation CAR design, an anti-CD25 scFv, or a CXCL12 receptor protein, but a T cell co-expressing a CAR protein targeting CD25 and a CXCL12 receptor protein on the cell membrane, which is not well known in the art. Thus, Teva does not apply to the instant case.
The instant specification fails to disclose sufficiently representative species of CAR proteins targeting CD25 for the vast genus claimed and does not disclose or demonstrate such CARs were well known in the art at the time of effective filing. Applicant mentions daclizumab and basiliximab in their Remarks as exemplary species of CD25 monoclonal antibodies known in the art at the time of effective filing, however, this argument is not persuasive because: 1) the claims are not limited to utilizing CD25 monoclonal antibodies or their sequences in the recited CAR, 2) the specification does not disclose these two daclizumab and basiliximab antibodies or their sequences, and does not disclose producing a CAR comprising their antigen-binding regions, or a T cell co-expressing the CAR with a CXCL12 receptor that functions as claimed; 3) the genus of sequences targeting CD25 required to make the claimed CAR and T cell that functions as claimed is vast; and 4) these two antibodies are not sufficiently representative of the vast genus of CD25-targeting sequences encompassed by the claimed CD25 CAR and T cell co-expressing it. Although Applicants argue that scFv sequences binding to CD25 were well known at the time of effective filing, Applicants are arguing limitations not recited in the claims. The claims do not recite a CD25 scFv, nor a CAR comprising one.
Prior Art
11. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Pratap et al. (Cancer Reports, 2020, e1222) discloses the use of engineered T cells with CARs for the treatment of AML. (See Pratap, pgs. 1-2 “Introduction”). Pratap teaches that CD25 may be a possible target for CAR T-cell therapy in AML. (See Pratap, pg. 6, column 1, paragraph 3).
However, Pratap is not cited as prior art because it fails to disclose an actual CAR T-cell targeting CD25 or the use of a CXCL12 receptor along with the CAR T cell therapy.
12. Conclusion: All claims are rejected.
Conclusion
13. THIS ACTION IS MADE FINAL. 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.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LINDSAY DUNN/Examiner, Art Unit 1642
/Laura B Goddard/Primary Examiner, Art Unit 1642
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