DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 04/02/2026, is acknowledged.
3. Claims 2-6, 8-9, 12, 16, 18-19, 21-22, 24, 26, 29, 31, 33, 35, 37, 38, 41, 43-48 are pending.
4. Applicant’s election without traverse of Groups I and IV , claims 2-6, 8-9, 12, 16, 18, 21, 37-38, 41, 44-48 directed to a guanylyl cyclase C (GCC) binding agent or anti-GCC CAR and a method of treating a cancer with a composition comprising anti-GCC CAR to a subject and the species of VH -CDRs of SEQ ID NOS: 10, 15, 18 and VH of SEQ ID NO: 28 and colorectal cancer, filed on 04/02/2026, is acknowledged.
5. Claims 22, 24, 26, 29, 31, 33, 35, 37-37, 41, 43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
6. Upon reconsideration, the Examiner has extended the search to cover all the species of anti-GCC single domain antibodies (VHH) recited in claims.
7. Claims 2-6, 8-9, 12, 16, 18, 21, 37-38, 41, 44-48 are under examination as they read on a guanylyl cyclase C (GCC) binding agent or anti-GCC CAR and a method of treating a cancer with a composition comprising anti-GCC CAR to a subject and the species of colorectal cancer.
8. Applicant’s IDS, filed 06/14/2024 and 04/02/2026, is acknowledged.
9. claim 12 is objected to because “CD8” is recited twice in the claim.
10. The following is a quotation of 35 U.S.C. 112(b) (Pre AIA , 35 U.S.C. 112, second paragraph):
(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.
11. Claims 2-6, 8-9, 12, 16, 18, 21, 37-38, 41, 44-48 are rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
(a) The recitations:
(i) “a heavy chain variable region (VH) with complementarity determining region (CDR) sequences of “ in claim 2;
(ii) “a heavy chain variable region (VH)” in claim 3;
(iii) “an immunoglobulin heavy chain variable (VH) region” in claim 4
(iv) “an immunoglobulin variable heavy chain” in claim 5; are ambiguous because the claims uses the language of conventional antibodies that normally pair with light chains, however the claimed anti-GCC antibodies are VHH antibody (nanobodies) known as single domain heavy chain antibodies (see Example 1 of the specification) derived from camelid heavy-chain-only antibodies.
(b) The recitation “the extracellular anti-GCC antigen binding domain is preceded by a leader nucleotide sequence encoding a leader peptide” in claim 6 is ambiguous for two reasons: (1) the extracellular anti-GCC antigen binding domain” lacks sufficient antecedent basis in base claim 2, claim 2 recites only “an extracellular antigen binding domain”. (2) the recitation of “a leader nucleotide sequence encoding a leader peptide” is indefinite because “the extracellular anti-GCC antigen binding domain” is limited to its amino acid component, it is not clear how the it will be preceded by a nucleotide sequence.
(c) The recitation “of claim 0” in claim 9 is indefinite because there is no claim 0.
12. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
13. Claims 37-38 and 41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating a colorectal cancer with anti-GCC CAR-T cells recited in claim 2, does not reasonably provide enablement for treating each and every cancer recited in claims 37-38 and 41. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The claims are directed to a genus of cancer treatments with anti-GCC CARs recited in claim or population of cells comprising the anti-GCC CARs recited in claim 2.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The specification fails to treat any cancer with a composition comprising the anti-GCC CAR of claim 2.
Besides Colorectal cancer, the specification fails to treat each and every cancer including gastrointestinal cancer, colorectal adenocarcinoma, colorectal leiomyosarcoma, colorectal lymphoma, colorectal melanoma, a colorectal neuroendocrine tumor, metastatic colon cancer, stomach cancer, gastric adenocarcinoma, gastric lymphoma, gastric sarcoma, esophageal cancer, squamous cell carcinoma, adenocarcinoma of the esophagus, or pancreatic cancer with population of cells comprising the anti-GCC CAR.
The specification fails to reducing tumor growth or tumor size by administering a population of cells comprising the anti-GCC CAR of claim 2 to a subject in need of treatment.
The specification under example 1 discloses isolation and selection of GCC VH antibodies. Single domain heavy chain antibodies (vH) were generated that specifically target human GCC (e.g., anti-GCC binders provided in Tables 1-3). As shown in Table 5, recombinant single domain anti-GCC VH constructs were assessed for binding affinity to GCC in vitro [0548].
PNG
media_image1.png
284
716
media_image1.png
Greyscale
Example 2 of the specification discloses design and characterization of GCC Chimeric Antigen Receptors. CAR T constructs are generated by linking the binder sequence in frame to CD28 hinge/transmembrane domains and costimulatory domain and CD3 zeta-1xx signaling domain (see [0552] and Fig. 1 A and 1B.
Example 3 of the specification describes anti-GCC CAR T cell activity in vitro. CAR-T cells expressing anti-GCC CARs (SEQ ID NO: 48-52) were examined for cytotoxicity against GCC-expressing and GCC-negative target cancer cell lines. The target cancer cell lines included GSU, LS1034 and HT55, which endogenously express GCC, as well as HT29-GCC, a human colorectal cancer cell line engineered to stably express GCC, and its vector control cell line that is GCC-negative, HT29-vec. VH anti-GCC binders exhibited cell killing against GCC-expressing target cell lines [0557].
Example 4 of the specification describes GCC CAR T cell activity in vivo. The antitumor activity of GCC CAR-T with different VH binders were studied in multiple human colorectal cancer tumor xenograft models expressing guanylyl cyclase C (GCC) endogenously. Non-obese diabetic/severe combined immunodeficient/γ-chain−/− (NSG) mice were inoculated subcutaneously with either HT55 cells, LS1034 cells, or GSU cells. When average tumor volume reached approximately 150 mm3, GCC CAR-T cells or mock T cells (non targeted CAR-T) were administered intravenously (IV) acutely. Different dose levels and donor sources were evaluated and indicated as shown in FIG. 8A-18. Tumor volume and body weight were measured twice weekly for up to 50 days. Acute IV administration of GCC CAR-T cells from multiple donors led to significant inhibition of tumor growth in all tumor models compared to their respective control group. There was no significant body weight loss observed in LS1034 or GSU tumor bearing NSG mice treated with GCC CAR T cells compared with their respective control group. In HT-55 tumor model, body weight loss observed is due to tumor burden. Tumor burden reduction post GCC CAR-T cell treatment results in body weight gain [0563].
Besides Colorectal cancer, the specification fails to treat each and every cancer including gastrointestinal cancer, colorectal adenocarcinoma, colorectal leiomyosarcoma, colorectal lymphoma, colorectal melanoma, a colorectal neuroendocrine tumor, metastatic colon cancer, stomach cancer, gastric adenocarcinoma, gastric lymphoma, gastric sarcoma, esophageal cancer, squamous cell carcinoma, adenocarcinoma of the esophagus, or pancreatic cancer with population of cells comprising the anti-GCC CAR. A CAR must be precisely matched to a tumor's specific GCC antigen to avoid "on-target, off-tumor" toxicities.
The MPEP states that the issue of "correlation" is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. See MPEP 2164.02.
The specification does not provide exemplification of animal model to treat each and every cancer with the claimed anti-GCC CAR-T cells.
Besides colorectal cancer, no effect of any therapy was administered to each and every cancer, with anti-GCC CAR-T cells.
The claims are directed to the use of any population cells comprising the anti-GCC CAR, however, not every cell expressing an anti-GCC CAR will work for treating colorectal cancer. The specification only discloses anti-GCC CAR -T cell in the treatment of colorectal cancer comprising specific CD28 hinge domain comprises SEQ ID NO: 29 and specific CD28 costimulatory domain comprises SEQ ID NO: 32.
The claims do not specify anti-GCC CAR comprises an extracellular domain, a transmembrane domain, and an intracellular domain
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
14. 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 conflicting claims 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); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
15. Claims 2-6, 8-9, 12, 16, 18, 21, 37-38, 41, 44-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 and 23-24 of copending Application No. 18256578 in view of WO2016044811.
The `578 application claims a guanylyl cyclase C (GCC) binding agent comprising: a heavy chain variable region (VH) with complementarity determining region (CDR) sequences of HYYWS (HCDR1) (SEQ ID NO: 8), RIYPSGSTSYNPSLKS (HCDR2) (SEQ ID NO: 11) and DRSTGWSEWNSDL (HCDR3) (SEQ ID NO: 16);a heavy chain variable region (VH) with complementarity determining region (CDR) sequences of RYWMS (HCDR1) (SEQ ID NO: 9), KIRHDGGEKYYVDSVKG (HCDR2) (SEQ ID NO: 12) and DYTRDV (HCDR3) (SEQ ID NO: 17);a heavy chain variable region (VH) with complementarity determining region (CDR) sequences of RYWMT (HCDR1) (SEQ ID NO: 10), KIKYDGSEKYYADSVKG (HCDR2) (SEQ ID NO: 13) and DYNKDY (HCDR3) (SEQ ID NO: 18);a heavy chain variable region (VH) with complementarity determining region (CDR) sequences of RYWMT (HCDR1) (SEQ ID NO: 10), KIRHDGGEKYYPDSVKG (HCDR2) (SEQ ID NO: 14) and DYNKDL (HCDR3) (SEQ ID NO: 19) or a heavy chain variable region (VH) with complementarity determining region (CDR) sequences of RYWMT (HCDR1) (SEQ ID NO: 10), KIRHDGGEKYYADSVKG (HCDR2) (SEQ ID NO: 15) and DYNKDY (HCDR3) (SEQ ID NO: 18), comprising an immunoglobulin heavy chain variable (VH) region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 or SEQ ID NO: 20;an immunoglobulin heavy chain variable (VH) regioncomprising an aminoacid sequence that is at least 90% identical to SEQ ID NO: 21;an immunoglobulin heavy chain variable (VH) region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 26; an immunoglobulin heavy chain variable (VH) region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 27; or an immunoglobulin heavy chain variable (VH) region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 28. A guanylyl cyclase C (GCC) binding agent comprising:an immunoglobulin heavy chain variable (VH) region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 or SEQ ID NO: 20;an immunoglobulin heavy chain variable (VH) regioncomprising an aminoacid sequence that is at least 90% identical to SEQ ID NO: 21;an immunoglobulin heavy chain variable (VH) regioncomprising an aminoacid sequence that is at least 90% identical to SEQ ID NO: 26;an immunoglobulin heavy chain variable (VH) region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 27; or an immunoglobulin heavy chain variable (VH) region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 28, wherein the VH region comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID Nos:1, 20, 21, 26, 27, or 28, wherein the VH region comprises an amino acid sequence that is identical to any one of SEQ ID NOs:1, 20, 21, 26, 27, or 28. The `578 application also claims methods of treating a cancer comprising administering the GCC binding agent of claim 1 to a subject in need of treatment, wherein the cancer is selected from gastrointestinal cancer, colorectal cancer, colorectal adenocarcinoma, colorectal leiomyosarcoma, colorectal lymphoma, colorectal melanoma, a colorectal neuroendocrine tumor, metastatic colon cancer, stomach cancer, gastric adenocarcinoma, gastric lymphoma, gastric sarcoma, esophageal cancer, squamous cell carcinoma, adenocarcinoma of the esophagus, or pancreatic cancer.
The claims of the `578 application differ for the instant claim only in the recitation of anti-GCC CAR and anti-GCC CAR-T cell.
WO2016044811 teaches chimeric transmembrane immunoreceptors (CAR), useful for producing a population of human T cells for treating cancer. The CAR include an extracellular domain that includes IL-13 or its variant that binds interleukin-13Ra2 (IL13Ra2), a transmembrane region, a costimulatory domain and an intracellular signaling domain. The invention further provides: (1) a population of human T cells transduced by a vector comprising an expression cassette encoding the CAR; (2) a method for treating cancer in a patient, by administering the population of autologous or allogeneic human T cells transduced by the vector; and (3) a nucleic acid molecule encoding an polypeptide. The present sequence represents a human CD28 costimulatory domain, which may be used for producing the population of human T cells for treating cancer. The `811 publication teaches human CD28 costimulatory domain of SEQ 27 which is identical to claim SEQ ID NO: 32 and specific spacer/hinge sequence, SEQ 17 identical to claimed SEQ ID NO: 29.
Those skilled in the art would have had a reason to incorporate the anti-GCC antibodies taught by the `578 application into the CAR construct and express it into cytotoxic CAR-T cell taught by the `811 publication to provide highly specific, MHC-unrestricted recognition of GCC on the surface of cancer cells that can directly recognize and destroy cancer cells.
This is a provisional nonstatutory double patenting rejection.
15. No claim is allowed.
16. The art made of record and not relied upon is considered pertinent to applicant's disclosure:
US 11932700 B2
The `700 patent claims a method of stimulating a T cell-mediated immune response and treating colorectal cancer in a human patient, the method comprising: contacting a population of cells comprising guanylate cyclase 2C (GUCY2C) comprising the amino acid sequence of SEQ ID NO: 33, in a human patient with a population of modified T cells comprising a chimeric antigen receptor (CAR), and stimulating a T cell-mediated immune response and treating colorectal cancer in a human patient, wherein the CAR comprises an extracellular domain, a transmembrane domain, and an intracellular domain, the extracellular domain comprising the amino acid sequences SEQ ID NO: 14, wherein the intracellular domain comprises a CD3 zeta signaling domain, wherein the intracellular domain further comprises a costimulatory signaling region comprising an intracellular domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, and any combination thereof, wherein the T cell-mediated immune response comprises release of one or more cytokines comprising IFNγ, wherein the modified T cells comprise natural killer T cells, wherein the modified T cells comprise cytotoxic T lymphocytes, wherein the modified T cells comprise regulatory T cells, wherein the modified T cells comprise human T cells, wherein the modified T cells comprise a polynucleotide encoding SEQ ID NO: 40.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
May 20, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
Prosecution Insights