Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election of the following species, in the reply filed on 28 August 2025 is acknowledged:
(1) IL-15 as the species of cytokine;
(2) inducible caspase 9 as the species of suicide gene;
(3) TGFBR2 as the species of modified gene; and
(4) lymphomas, AML and renal cell cancer as the species of cancer.
Applicant’s election of SEQ ID NO: 7 as the species of fully-defined CD70-specific engineered receptor, in the reply filed on 23 December 2025 is also acknowledged.
Status of Application, Amendments, and/or Claims
3. The Responses filed on 28 August 2025 and 23 December 2025 have been entered in full. Claims 33 and 37-39 have been canceled. Therefore, claims 1-3, 5, 7, 9, 14-15, 17-21, 25, 27 and 30-31 are pending and the subject of this Office Action. The claims also read on the elected species set forth supra and have been examined to the extent they read on such.
Information Disclosure Statement
4. The information disclosure statements (IDS) submitted on 02 August 2022, 22 August 2022, 30 April 2024, 16 July 2024, 23 September 2024, 15 October 2024, 27 December 2024, 29 January 2025, 03 November 2025, 17 December 2025, 23 December 2025, and 26 January 2026 have been considered by the Examiner.
Improper Markush
5. Claims 9, 14-15, 17 and 30 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of costimulatory domains, cytokines, suicide genes, modified genes, and the chimeric antigen receptors (CAR) comprising them is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: Claims 9, 14-15, 17 and 30 (and claims dependent thereon) are directed to nucleic acids encoding CARs which comprise domains of various different proteins. The nucleic acid sequences of the various domains (i.e., costimulatory domains, cytokines, suicide genes, modified genes) are different and thus share no structural similarity and therefore, there is no substantial structural feature and a common use that flows from the substantial structural feature.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112, 1st Paragraph (Written Description)
6. 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.
7. Claims 1-3, 5, 7, 9, 14-15, 17-21, 25, 27 and 30-31 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
8. The U.S. Court of Appeals for the Federal Circuit recently reaffirmed, in an en banc decision, that the written description requirement for a genus may be satisfied either by (i) the disclosure of a representative number of species falling within the scope of the genus or (ii) 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 Pharmaceuticals', Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350, 94 U.S.P.Q.2d 1161, 1171 (en banc) (Fed. Cir. 2010), citing Regents" of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568-69, 43 U.S.P.Q.2d 1398, 1406 (Fed. Cir. 1997).
9. The representative ways of satisfying the written description requirement as set out by the Federal Circuit in Ariad Pharmaceuticals comport with statements set out in the USPTO's Manual of Patent Examining Procedure (M.P.E.P.). In particular, the M.P.E.P. provides that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species of relevant identifying characteristics. M.P.E.P. § 2163, II, A, 3, (a), (ii).
10. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. “Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163.
11. In the instant case, the claims are drawn quite broadly to an expression construct comprising sequence that encodes a CD70-specific engineered receptor and that encodes one or both of the following:(a) a suicide gene; and (b) a cytokine. The claims also recite wherein the CD70-specific CAR comprises a codon optimized scFv or a humanized scFv; or wherein the CD70-specific CAR comprises one or more costimulatory domains, wherein the costimulatory domain is selected from the group consisting of CD28, CD27, OX-40 (CD134), DAP10, DAP12, 4-1BB (CD137), CD40L, 2B4, DNAM, CS1, CD48, NKG2D, NKp30, NKp44, NKp46, NKp80, and a combination thereof; or wherein the cytokine is IL-15, IL- 12, IL-2, IL-18, IL-21, IL-7, or a combination thereof; or wherein the suicide gene is a mutant TNF-alpha, inducible caspase 9, HSV-thymidine kinase, CD 19, CD20, CD52, or EGFRv3. The claims also recite an immune cell comprising the expression construct, wherein expression of one or more endogenous genes in the immune cell has been modified, wherein the gene is selected from the group consisting of NKG2A, SIGLEC-7, LAG3, TIM3, CISH, FOX0l, TGFBR2, TIGIT, CD96, ADORA2, NR3C1, PD1, PDF-1, PDF-2, CD47, SIRPA, SHIP1, ADAM 17, RPS6, 4EBP1, CD25, CD40,IF21R, ICAM1, CD95, CD80, CD86, IF10R, CD5, CD7, CTFA-4, TDAG8, CD38, and a combination thereof. Thus, the claims are drawn to an extremely large genus of expression constructs encoding chimeric antigen receptors that are only defined by a very limited partial structure. However, the specification does not provide sufficient written description as to the structural features of the claimed genus of chimeric antigen receptors that is encompassed by the claims.
12. For genus claims, an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. A patent must set forth either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. Kubin, Exparte, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007); Ariad Pharms., Inc. v. Eli Lilly& Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010).
A “patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”), see MPEP 2163.IIAii.
13. 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. For example, quoting Eli Lilly the court states in Ariad, 598 F.3d at 1350: "[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." (quoting Eli Lilly, 119 F.3d at 1568-69).
14. A "representative number of species" means that the species, which are adequately 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)(Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
15. In the instant case, the claims encompass in their breadth expression constructs encoding a CD71-specific CAR that encodes one or both of a suicide gene and a cytokine, with no requirement for any particular structural feature of the recited cytokine, suicide gene, codon optimized scFv or humanized scFv, costimulatory domain which comprise the CAR, or any particular structural or functional feature for the “modified” endogenous genes of the cell comprising the CAR.
16. Given the exceedingly large genus of components which make up the CAR, one of skill in the art cannot possibly envision which structures contained within this genus will be capable of functioning as a CD70-specific CAR. With the exception of claim 7, the claims do not even require a component that would produce a CAR that was CD70-specific (i.e., a CD70-binding domain or molecule).
17. In contrast to the breadth of the claims, the specification describes 4 species of expression constructs encoding CD70-specific CARs that are defined by particular nucleic acid sequences for each of the “domains”: a 42D12 scFv, a CD28 costimulatory domain, a CD3 zeta transmembrane domain, and IL-15. Specifically, that Specification discloses CO CAR.CD70 42D12. VLVG.IgG1.CD28.CD3z-2A-IL15 (SEQ ID NO: 7), CO CAR.CD70 42D12 VHVL.IgG1.CD28.CD3z-2A-IL15 (SEQ ID NO: 8), CAR.CD70 42D12 VLVH.IgG1.CD28.CD3z-2A-IL15 (SEQ ID NO: 9), and CAR.CD70 42D12 VHVL.IgG1.CD28.CD3z-2A-IL15 (SEQ ID NO: 13), which the Specification discloses as exhibiting anti-tumor activity when transduced in NK cells (See Example 1; Figures 6 and 7, for example). However, there does not appear to be an adequate written description in the Specification as filed for the exceedingly large genus of expression constructs encoding a CD71-specific CARs encompassed by the claims, with no requirement for any particular structural feature of the recited cytokine, suicide gene, transmembrane domain, codon optimized scFv or humanized scFv, costimulatory domain, that which makes it CD70-specific, or for the “modified” endogenous genes of the cell comprising the CAR.
18. While generically the structure of antibodies is known, the structure of the presently recited antibodies to be produced and screened can vary substantially. As noted in Amgen, knowledge that an antibody binds to a particular antigen or a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of CD70 binding molecules encompassed by the claims, nor the codon optimized scFv or humanized scFv recited in the claims.
19. Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
20. An adequate written description of a chemical invention requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”). See MPEP 2163IIA3(a).
21. Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of expression constructs encoding CD70-specific CARs encompassed in the breadth of the instant claims.
22. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that in order to satisfy the written description requirement, “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). As discussed above, the skilled artisan cannot envision the detailed structure of the encompassed genus of expression constructs encoding CD70-specific CARs, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
23. Therefore, Applicant has not disclosed sufficient species or common structural features
such that one skilled in the art would conclude that Applicant was in possession of the claimed
genus of expression constructs encoding a CD70-specific CARs encompassed by the claims. Accordingly, claims 1-3, 5, 7, 9, 14-15, 17-21, 25, 27 and 30-31 do not meet the written description provision of 35 U.S.C. §112a) or 35 U.S.C. 112 (pre-AIA ) first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 102
24. 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.
25. 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)(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.
26. Claim(s) 1-2, 7, 9, 15, 18-19 and 31 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Wang et al (US 2018/0208671; published 26 July 2018; cited by Applicant).
27. Wang et al. disclose an expression construct encoding a CD70-specific engineered chimeric antigen receptor (CAR) that comprises an antigen-binding CD27 transmembrane domain, a CD3zeta costimulatory domain, and the suicide gene HSV-thymidine kinase (See Abstract; claim 1; pg. 8 [0064]). Wang et al. also disclose immune cells transduced with the CAR, including T cells and B cells, and a population thereof present in a culture medium (See pg. 8 [0065]-[0067]; claim 16). Thus the reference of Wang et al. meets all the limitations of claims 1-2, 7, 9, 15, 18-19 and 31.
Double Patenting
28. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
29. A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
30. The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
31. Claims 1-2, 7, 9, 14, 18-21, 25 and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-96 of U.S. Application No. 18/700,483 (reference application). Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the reference application are drawn to expression constructs encoding a CD70-specific chimeric antigen receptors, comprising an antigen-binding region, a costimulatory domain, a signal peptide, and a cytokine (including IL-15, IL-2, IL-12, IL-18, IL-21), as well as immune cells comprising said CAR, and compositions comprising the same. Therefor the instant claims are obvious over the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
32. Claims 1-2, 7, 9, 14, 18-21, 25 and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Application No. 18/699,702 (reference application). Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the reference application are drawn to expression constructs encoding a CD70-specific chimeric antigen receptors, comprising an antigen-binding region, a costimulatory domain, a signal peptide, and a cytokine (including IL-15, IL-2, IL-12, IL-18, IL-21), as well as immune cells comprising said CAR, and compositions comprising the same. Therefor the instant claims are obvious over the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
33. Claims 1-3, 5, 7, 9, 14, 18-21, 25 and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 57-160 of U.S. Application No. 18/567,967 (reference application). Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the reference application are drawn to expression constructs encoding a CD70-specific chimeric antigen receptors, comprising an antigen-binding region (an scFv), a costimulatory domain, a signal peptide, and a cytokine (including IL-15, IL-2, IL-12, IL-18, IL-21), as well as immune cells comprising said CAR, and compositions comprising the same. Therefor the instant claims are obvious over the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Summary
34. No claim is allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JON M LOCKARD whose telephone number is (571) 272-2717. The examiner can normally be reached M-F 9-6 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached on (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JON M LOCKARD/Examiner, Art Unit 1647 April 30, 2026
Prosecution Insights