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 .
Election/Restrictions
Applicant's election with traverse of Group I, drawn to a CAR that binds CD7 in the reply filed on 19 April 2026 is acknowledged. Applicant argues Group I and Group II are not patently distinct. Examiner agrees. The restriction between Group I and Group II is withdrawn.
Applicant's election with traverse of SEQ ID NO:5 of a CD-7-L based CAR in the reply filed on 19 April 2026 is acknowledged. The traversal is on the ground(s) that claims 1-9, 14, and 19-20 are generic claims that should be properly examined together and points to MPEP 806.04(b), applicant states “The Examiner identified two representative species based on the antigen recognition domain:” then listed a species A and species B where A comprised a CAR comprising a CD7 ligand and B comprised a CD7 binding scFv. Applicant argues the function of binding CD7 make the species not patentably distinct and the same inventive disclosure. Applicant argues “both” species are described and there would be no search burden for “both”.
This is not found persuasive because:
Regarding MPEP 806.04(b), examiner points to “For example, two different subcombinations usable with each other may each be a species of some common generic invention. If so, restriction practice under election of species and the practice applicable to restriction between combination and subcombinations must be addressed.” The CD7 CAR of the claims is not restricted between and was instead an election of species was done. See the office action dated 02/27/2026 and response to arguments below regarding an election of species being proper in this case.
Examiner does not identify 2 species, there are 2 subgroupings of the genus of the claims they are a CAR comprising a CD7 binding ligand and a CD7 binding scFv. Each CD7 binding ligand would be its own species and each scFv that binds CD7 would be its own species. There is a search burden as each scFv requires a different search of the sequence databases as its binding activity are from unique VH and VL for that scFv. The search of each possible VH and VL of the claims would not provide a search for a ligand binding scFv as they do not comprise the structures of an scFv and derive their binding activity from unique amino acids sequences and structures.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7-9, 16, and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04/19/2026.
Claim Status
Claims 1-20 as filed on 12 July 2023 are pending. Claims 7-9, 16, and 20 are withdrawn. Claims 1-6, 10-15, and 17-19 are under examination.
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 1-6, 10-14, and 19 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or it may be satisfied by the disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
Scope of the Claimed Genus
Claim 1 is to a CAR comprising a CD7 targeted antigen recognition domain that has at least 90% sequence identity of instant SEQ ID NO: 5. Instant SEQ ID NO: 5 is 145 amino acids in length and encodes the extracellular domain of K12/SECTM1, a 90% identity requirement allows for 14 amino acid changes anywhere in the sequence. The CD7 bound by the claims can be from any species.
Claims 2-6 does not provide further limitations for the antigen recognition domain.
Claims 4-6 and 10 comprise a CD7 blocking domain. Claims 4-5 do not provide any structure for this blocking domain but limits the domain to a blocking domain that binds CD7. Claim 6 includes CD7-L extracellular domains that are at least 90% sequence identity to SEQ ID NO: 5.
Claim 10 is to any CD7 blocking domain that has at least 90% sequence identity with the human CD7-L extracellular domain.
Claims 11-14 do not provide further limitations to the CD7 blocking molecules or the CD7 targeted antigen.
Claim 19 does not provide any further limitations to the structure of CD7 binding domain.
Summary of Species Disclosed in the original specification
Applicant discloses a CD7-L that binds CD7 and functions in a CAR as required by the claims, it is of instant SEQ ID NO: 5 and shown in Figures 2-3, this sequence also worked in the blocking domain CD-7-L ER2.1 in Figures 2-3.
Applicant additionally discloses the scFv of TH69 shown in instant SEQ ID NO: 8. Applicant discloses its binding activity as both an antigen binding domain in a CAR and in a CD7 blocking domain (Figures 2-3).
The CARs of the disclosure all comprise fully defined sequence of the antigen binding domain and the CD7 blocking domains all comprise fully defined sequences for the CD7 binding domain. Applicant does not disclose any sequence variation or identify any core amino acids for the antigen binding domains or CD7 blocking molecules.
State of the Relevant Art
CD7 is a 40-kDa protein found primarily on T cells, NK cells, and pre-B cells. K12(SECTM1 which matches instant SEQ ID NO: 5) is a transmembrane domain that binds CD7 (Lymann et. al. Journal of Biological Chemistry. 275(5):P3431-3437 (2000) (PTO-892) (abstract and Figures 1-4). The mouse K12 protein is 212 amino acids in length and shares 36% identity with the human K12 protein (page 3431 in col 2 in par 2) and 44% amino acid identitites in their extracellular domains (page 3433 in lines 1-2). The extracellular domain of the human K12 is 145 amino acids in length, the mouse K12 is 160 amino acids in length (page 3431 in col 2 in par 4). Lymann identified multiple regions of conserved sequences between human and mouse K12 (Figure 3). Lymann teaches that human K12 extracellular domain shares 44% identity with the amino acid sequence of the mouse K12 extracellular domain and that human K12 does not bind mouse CD7 and mouse K12 does not bind human CD7, house and human CD7 share 49% identity in their extracellular domain sequences (page 3433 in lines 1-20 and Figure 5). Thus, the binding of K12 to CD7 likely relies on its amino acid sequence.
The binding of K12 to CD7 remains not fully known in the art in the time following Lymann’s early work. It is known that CD7 functions as a costimulatory receptor for T cell proliferation. K12(SECTM1) is a type I transmembrane glycoprotein and exists as a transmembrane and soluble protein. SECTM1 comprises two Ig-like domains at the N-terminus and one N-linked glycosylation motif. The full biological consequences of SECTM1 binding CD7 is not fully defined (Wang et. al. JLB. 91:449-459. (2012) (PTO-892) (abstract and page 450 in col 1 in par 1-2). SECTM1 enhances T cell activation including CD7 positive cells (Figures 3 and 6).
While it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with reasonable expectation of success are limited. It is art known that certain residues are shown to particularly important to the biological or structural properties of a protein or peptide, e.g., residues in active sites and such residues may not be generally be exchanged. Skolnick et al teach that sequence-based methods for function prediction are inadequate and knowing a protein's structure does not tell one its function (Skolnick, et al. Trends in Biotech. 18, 34-39, 2000, see abstract, in particular)(PTO-892) and Leninger et al. (Elife. 2019;8:e48909. 1-16(2019)) (PTO-892) (abstract).
The art teaches that K12 is a ligand that binds CD7 and teaches that differences in the amino acid sequence of human versus mouse K12 changes its binding activity. This is supported by the art knowledge of changes to amino acid sequences of proteins.
Are the disclosed species representative of the claimed genus?
MPEP § 2163 states that 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 specification discloses a CD-7 ligand that binds CD7 of SEQ ID NO: 5 which is the extracellular domain of K12(SECTM1) known in the art to bind human CD7.
The specification and art show that variability in the sequence of K12 would result in unknown changes to binding to CD7.
The species disclosed cannot be considered representative of the genus.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that the skilled artisan as of the effective filing date would have expected to convey the claimed binding activity.
Applicant has not identified the core amino acids of instant SEQ ID NO: 5 needed to bind CD7 either in humans or CD7 more broadly as claimed, this is also not found in the art as the art only supports changes to the sequence changing binding activity and does not identify what core sequence is required for binding.
The variation of the sequences in the claims means the claims do not have a structure/function correlation.
Conclusion:
The claims are to an antigen recognition domain that binds CD7. It does not limit the species if origin for CD7. It is limited to at least 90% identity of instant SEQ ID NO: 5 which is the extracellular domain of human K12. The art teaches that sequence identity of CD7 and K12 varies between species and that binding by K12 depends on the sequence of K12. Neither the specification nor the art teaches which amino acid substitutions in instant SEQ ID NO: 5 would change its binding activity. The applicant has only provided one working example of a ligand that binds human CD7 and that is the complete sequence of instant SEQ ID NO: 5 and has not identified the core structure of that 145 amino acid sequence provide this function.
Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, Applicant was not in possession of the invention as claimed.
Claim Rejections - 35 USC § 103
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.
Claims 1-3 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Urbanska et al. Cancer Res. 72(7):1844-1852. (2012) (PTO-892), Helfrich & Bremer. Methods in Molecular Biology: Chapter 7: Bifunctional Antibody Fragment-Based Fusion Proteins for Targeted Elimination of Pathogenic T-cell subsets. (2014) (“Helfrich” PTO-892), and Lymann (US 6762030) (PTO-892).
Regarding claims 1-3, Urbanska teaches a CAR T cell where the CAR comprises a binding domain for a tumor-associated antigen (TAA) where the binding domain is an extracellular domain of the CAR and is ligand that binds the receptor of interest (abstract). Urbanska teaches the CAR comprises a CD8α hinge and transmembrane domain, a CD28 intracellular co-stimulaotry domain, and a CD3 zeta domain (Figure 1).
Regarding claim 19, Urbanska teaches the treatment of cancer targeting the antigen bound by the ligand of the CAR (abstract).
Urbanska does not teach the use of the CD7 binding ligand K12.
This deficiency is filled by Helfrich and Lymann.
Helfrich teaches CD7 binding molecules for targeting T cells in treatment of cancer to eliminate pathogenic immune cells (abstract and Figure 1). Helfrich teaches the substitution of a CD7 binding scFv with a natural ligand that binds CD7 and explicitly teaches K12 is just as effective as an scFv in targeting CD7 on T cells (page 91 in “Notes” 1).
Lymann teaches a ligand for CD7 including K12 proteins of SEQ ID NO: 4 which matches instant SEQ ID NO: 5 as shown below (abstract col 3 in lines 44-52). Lymann teaches the use of the K12 protein can be used in method of treating disease associated with CD7 expression (col 9 in lines 60-67 and col 10 in lines 1-2). Lymann teaches K12 binding of CD7 can be used in therapeutic applications including the treatment of cancer (abstract and col 16 in lines 49-62 in particular lines 56-59).
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It would have been obvious at the time the application was filed to substitute the generic ligand that binds TAA of the CAR of Urbanska with the CD7 binding ligand of K12 taught by Helfrich and Lymann to produce a CAR comprising a CD7 binding extracellular domain of K12, a CD8α hinge and transmembrane domain, with a CD28 intracellular co-stimulatory domain, and a CD3 zeta domain. The substitution of the generic ligand that binds a TAA of Urbanska with the CD7 binding ligand K12 would be prima facie obvious as art equivalent substitutions where K12 performs the same biological activity of binding a TAA that Urbanska requires for the ligands of the CARs of their invention (see MPEP 2183). One of skill in the art would have been motivated by the teachings of Helfrich that scFv can be substituted with K12 for binding CD7 and the teachings of Lymann and Helfrich that K12 is an effective binder of CD7 in the treatment of cancer. There would have been a reasonable expectation of success as Urbanska explicitly teaches the substitution of the ligand domain of its CAR and Helfrich and Lymann teach the effective binding of CD7 by K12.
Claims 1, 4-6, 10-15, and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Urbanska et al. Cancer Res. 72(7):1844-1852. (2012) (PTO-892), Helfrich & Bremer. Methods in Molecular Biology: Chapter 7: Bifunctional Antibody Fragment-Based Fusion Proteins for Targeted Elmintation of Pathogenic T-cell subsets. (2014) (“Helfrich” PTO-892), and Lymann (US 6762030) (PTO-892) as applied to claims 1-3 and 19 above, and further in view of Gomes-Silva et al. Immunobiology. 130(3):285-296. 2017 (PTO-892) and Png (US 20180148506 A1) (IDS).
The teachings of Urbanska from the previous art rejection is incorporated here in full.
Regarding claims 11-12, Urbanska teaches a vector encoding the CAR that is a lentiviral vector (page 1845 in col 1 in par 2-3).
The teachings of Helfrich and Lymann are incorporated here in full.
Urbanska in view of Helfrich and Lymann teaches a CAR comprising a K12 ligand that binds CD7, a CD8α hinge and transmembrane domain, with a CD28 intracellular co-stimulatory domain, and a CD3 zeta domain for use in the treatment of cancer.
Urbanska in view of Helfrich and Lymann does not teach a modified or engineered cell comprising the CD7 binding CAR further comprises a CD7 blocking molecule that prevents CD7 from being transported to the cell surface by intracellular anchoring.
This deficiency is filled by Gomes-Silva and Png.
Gomes-Silva teaches the CAR T cell therapy for T-cell malignancies faces the issue of most target antigens are shared between normal and malignant cells leading to CAR T-cell fratricide. Gomes-Silva teaches CD7 is a transmembrane protein highly expressed in leukemia and lymphoma and that disruption of CD7 expression in CAR t cells prevented fratricide and enabled the expansion of CD7 binding CAR T cells without compromising their cytotoxic function (abstract). Gomes-Silva teaches the same method worked in CD5-specific CARs (page 285 in col 1 in par 3).
Png teaches a modified or engineered CAR T cell that comprises an anti-CD7 CAR an anti-CD7 protein blocker for use in cancer therapy (abstract and claims 66 and 73).
Png teaches that one of skill in the art recognizes that fratricide of CAR T cells and killing of normal T cells can arise from CAR T cells used in treating leukemias (0034]). Png teaches engineered CAR T cells that use the anti-CD7 PEBL and anti-CD7 CAR T cells that elicit a potent and durable therapeutic effects in patients with T cell malignancies ([0035]). Png teaches the anti-CD7 PEBL has an ER retention method for use with the anti-CD7 CAR (Figure 1).
Regarding claim 12, Png teaches the use of vectors comprising the modifications including retroviral vectors ([0038]).
Regarding claim 13, Png teaches the use of ribosome entry sites in cell modification ([0153]).
Regarding claim 14, Png teaches a kit comprising the vectors of the invention and kits with one or more reagents ([0130]-[0132]).
Regarding claim 15, Png teaches the CD7-PEBl which is the CD7 plus ER retention sequence of instant SEQ ID NO: 10 (Figure 1).
It would have been obvious at the time the application was filed to combine the CD7 binding CAR T cell of Urbanska in view of Helfrich and Lymann with the method of CD7 protein blocking with CD7 PEBL of Png. One of skill in the art would have been motivated by the teachings of Gomes-Silva and Png to disrupt CD7 in the CAR T cells that target CD7 to avoid fratricide and produce a more robust CAR T cell population that expands and persists in patients. There would have been a reasonable expectation of success as Gomes-Silva and Png teach two different CAR T cells targeting CD7 with CD7 knockout cells function as therapeutics and Gomes-Silva shows the knockout method worked with different CARs making it more likely to work with the ligand comprising CAR of the claims.
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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