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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 13 February 2014 and 12 June 2025 comply with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings are objected to because the text in Figure 1 is blurred and unclear. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 4 is objected to because of the following informalities: Claim 4 recites, “an amino acid sequence selected from SEQ ID NOS: 1-3, 7-12, 23, 25-27, 31-33,” which is missing the word “or” at the end of the list of alternatives. Appropriate correction is required.
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.
Claims 1-15, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Kuball et al. (US 2019/0271688) in view of Sewell et al. (US 2020/0316124).
Kuball et al. (US 2019/0271688), hereinafter Kuball (688), teaches a method for treating a cancer in a subject in need thereof, the method comprising: administering to the subject a pharmaceutical composition comprising an engineered αβ T-cell that expresses an exogenous γ9δ2T-cell receptor or a functional fragment thereof as well as a pharmaceutically acceptable carrier (see claims 13 and 17). The composition is further claimed as a means for treating solid tumor cancer cells (see claim 5).
As such, it is the objective of Kuball (688) to use an engineered immune responsive αβ T-cell that comprises or expresses an exogenous γ9δ2T-cell receptor or a functional fragment thereof to treat solid cell cancers. Specifically, Kuball (688) teaches that the method may treat cancers including myeloma, leukemia, osteosarcoma, renal cell carcinoma, head and neck cancer, breast cancer, and colon cancer (see [0128]). Kuball (688) does not, however, explicitly teach a method of treating ovarian cancer.
Sewell teaches a method of treating cancer, including colorectal cancer, lung, kidney, cervical, melanoma, bone, breast, blood cancer, brain, ovary, head and neck, and others, by administering to a subject a T-cell comprising a vector encoding a specific T-cell receptor (TCR) wherein the TCR comprises a γ chain and a δ chain and the T-cell expresses the TCR (see [0030]).
Regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Kuball (688) as taught by Sewell to treat ovarian cancer. One would be motivated to use the method of Kuball (688) to treat ovarian cancer with a reasonable expectation of success because the types of cancers taught in the two references overlap. As mentioned above, both references teach methods for treating cancers of the head, neck, breast, blood, and colon, but Sewell further teaches that the method can treat ovarian cancer. Recognizing that the references use the same TCR for the treatment of several of the same cancers and that Sewell expressly suggests treating ovarian cancer, a skilled artisan would have been motivated to use Kuball (688)’s engineered immune responsive cells to treat ovarian cancer.
With regard to claim 2, Kuball (688) teaches that the composition can be used with a pharmaceutically acceptable adjuvant, carrier or diluent (see claim 13). ,
With regard to claim 3, Kuball (688) teaches that the engineered immune responsive cell is an αβ T-cell that expresses an exogenous γ9δ2T-cell receptor or a functional fragment thereof (see claim 17).
With regard to claim 4,Kuball (688) teaches a T-cell receptor or fragment thereof with two polypeptides, γ9 and δ2 polypeptide chains, and Kuball (688) teaches at least SEQ ID numbers 1-3, 7-15, and 19-36 with 100% sequence similarity (see [0058]). As such, Kuball (688) teaches the two polypeptide chains, γ9 and δ2, chains of claim 4.
With regard to claim 5, the γ9 and δ2 receptor or receptor fragments taught by Kuball (688) further contain complementary-determining regions (CDRs), particularly CDR3 (see [0052]). Specifically, Kuball (688) teaches the SEQ ID numbers 19-24 and 7-12 with 100% similarity and therefore teaches the CDR3 region contained within those sequences.
With regard to claim 6, Kuball (688) teaches the use of αβ T-cells that express an exogenous γ9δ2T-cell receptor or a functional fragment thereof (see [0051]).
With regard to claims 7-10, Kuball (688) teaches a T-cell receptor or fragment thereof with two polypeptides, γ9 and δ2 polypeptide chains, and Kuball (688) teaches at least SEQ ID numbers 1-3, 7-15, and 19-36 with 100% sequence similarity (see [0058]). As such, Kuball (688) teaches the two polypeptide chains, γ9 and δ2, chains of claims 7-10 with at least 95% sequence similarity.
With regard to claim 11, Kuball (688) teaches that the composition can be administered intravenously to the subject (see claim 20).
With regard to claims 12-14, these claims are intended result claims, which only limit the process where the clause gives meaning and purpose to the manipulative steps. With regard to claim 12 Kuball (668) teaches administering compositions with 100% sequence similarity in the same manner to the subjects. Here, a person of ordinary skill in the art would reasonably expect to see the same results, reduction in the number of ovarian cancer cells, seeing as they employ the same method with the same compositions and have the previously established motivation to treat ovarian cancer. Similarly, with regard to claims 13 and 14, cytotoxicity to ovarian cancer cells (claim 13) and reduction of ovarian cancer cell growth (claim 14) are necessarily implied in the invention claimed by Kuball (688) because Kuball (688) has a previously established motivation to treat the same disease with the same method and the same compositions. One of ordinary skill in the art would therefore expect the same results, cytotoxicity for ovarian cancer cells and reduction in ovarian cancer growth.
With regard to claim 15, Kuball (688) does not teach administering to the subject an additional anti-cancer in combination with the composition that Kuball (688) claims. Sewell does, however, teach administering to the subject an anti-cancer therapy in combination with their claimed composition. Both references teach methods for using TCR receptors or fragments thereof to treat cancers of the head, neck, breast, blood, and colon, but Sewell further teaches a treatment for ovarian cancer and that the treatment can include additional anti-cancer therapies. Recognizing that the references overlap in using the same TCR for the treatment of several of the same cancers and that Sewell expressly suggests using additional anti-cancer therapeutics, a skilled artisan would have been motivated to use Kuball (688)’s engineered immune responsive cells in combination with additional anti-cancer therapies to treat ovarian cancer.
With regard to claim 20, Kuball (688) teaches results for a safe and functional treatment for a humanized model (see [0130]). Kuball (688) does not, however, expressly teach the treatment of human subjects. Though Kuball (688) doesn’t explicitly teach a treatment for human subjects, Kuball (688) does teach promising results when treating a humanized model. Specifically, Kuball (688) teaches intravenously treating humanized mouse models, which showed reduced tumor growth after treatment. Given this motivation from the humanized model demonstrated in Kuball (688), it would have been obvious to a person of ordinary skill in the art before the effective filing date to use this motivation and try the treatment on human subjects.
Claims 1 and 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Kuball et al. (US 2019/0271688) and Kuball et al. (US 2019/0169260).
As discussed above, Kuball (688) teaches a method for treating a cancer in a subject in need thereof, the method comprising: administering to the subject a pharmaceutical composition comprising an engineered αβ T-cell that expresses an exogenous γ9δ2T-cell receptor or a functional fragment thereof as well as a pharmaceutically acceptable carrier (see claims 13 and 17). The composition is further claimed as a means for treating solid tumor cancer cells (see claim 5).
As such, it is the objective of Kuball (688) to use an engineered immune responsive αβ T-cell that comprises or expresses an exogenous γ9δ2T-cell receptor or a functional fragment thereof to treat solid cell cancers. Specifically, Kuball (688) teaches that the method may treat cancers including myeloma, leukemia, osteosarcoma, renal cell carcinoma, head and neck cancer, breast cancer, and colon cancer (see [0128]). Kuball (688) does not, however, explicitly teach a method of treating ovarian cancer.
Kuball et al. (US 2019/0169260), hereinafter Kuball (260) teaches a polypeptide composition with a γδT-cell receptor to treat cancer (see claim 64). Kuball (260) teaches a very similar method as compared to Kuball (688) insofar as Kuball (260) uses αβ T-cells engineered to express the γδT-cell receptor to treat cancers, including ovarian cancer, head and neck cancer, breast cancer, cervical cancer, and many more (see [0078] and claims 25 and 30).
Regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Kuball (688) as taught by Kuball (260) to treat ovarian cancer. One would be motivated to use the method of Kuball (688) to treat ovarian cancer with a reasonable expectation of success because the types of cancers taught in the two references overlap. As mentioned above, both references teach methods for treating cancers of the head, neck, breast, but Kuball (260) further teaches that the method can treat ovarian cancer. Recognizing that the references use the same TCR for the treatment of several of the same cancers and that Kuball (260) expressly suggests treating ovarian cancer, a skilled artisan would have been motivated to use Kuball (688)’s engineered immune responsive cells to treat ovarian cancer.
With regard to claim 15, Kuball (260) teaches a method of treating cancer by administering to a subject an additional anti-cancer therapy along with the γδT-cell receptor treatment.
With regard to claim 16-18, Kuball (260) further teaches that the composition comprises or is capable of expressing the γδT-cell receptor can be administered before, concurrent with, or after additional anti-cancer therapies (see [0123]).
With regard to claim 19, Kuball (260) teaches that the additional anti-cancer therapies can be radiation or chemotherapy or a combination thereof (see [0007]).
Double Patenting
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.
Claims 1-15 and 19 are rejected on the ground of non-provisional nonstatutory double patenting as being unpatentable over claims 5, 13, 17, 20, 21, and 24 of U.S. Patent No. 11686724in view of Sewell et al. (US 2020/0316124).
U.S. Patent No. 11686724, hereinafter Kuball (397), claims a method of treating cancer comprising administering to a subject an engineered αβ T-cell that expresses an exogenous γ9δ2T-cell receptor (see claim 17). Kuball (397) further claims the composition for treating solid cancer cells, including renal cell carcinoma, myeloma, leukemia, head and neck cancer, and colon cancer, but Kuball (397) does not claim the use of the composition for treating ovarian cancer (see claim 5 and [0122]).
Sewell teaches a method of treating cancer, including colorectal cancer, lung, kidney, cervical, melanoma, bone, breast, blood cancer, brain, ovary, head and neck, and others, by administering to a subject a T-cell comprising a vector encoding a specific T-cell receptor (TCR) wherein the TCR comprises a γ chain and a δ chain and the T-cell expresses the TCR (see [0030]).
Regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Kuball (397) as taught by Sewell to treat ovarian cancer. One would be motivated to use the method of Kuball (397) to treat ovarian cancer with a reasonable expectation of success because the types of cancers taught in the two references overlap. As mentioned above, both references teach methods for treating cancers of the head, neck, breast, blood, and colon, but Sewell further teaches that the method can treat ovarian cancer. Recognizing that the references use the same TCR for the treatment of several of the same cancers and that Sewell expressly suggests treating ovarian cancer, a skilled artisan would have been motivated to use Kuball (397)’s engineered immune responsive cells to treat ovarian cancer.
With regard to claim 2 of the instant application, Kuball (397) claims composition comprising an engineered αβ T-cell that comprises an exogenous γ9δ2T-cell receptor, and a pharmaceutically acceptable adjuvant, carrier or diluent (see claim 13). With regard to claim 3 of the instant application, Kuball (397) claims administering to the subject a pharmaceutical composition comprising an engineered αβ T-cell that expresses an exogenous γ9δ2T-cell receptor of a functional fragment thereof (see claim 17).
With regard to claim 4 of the instant application, Kuball (397) teaches a γ9δ2T-cell receptor with first and second polypeptides, namely γ9TCR and δ2TCR chains, and Kuball (397) teaches all of the sequences for the polypeptides that are claimed in the instant application, SEQ ID numbers 1-36 with 100% sequence similarity (see claim 24).
With regard to claim 5, Kuball (397) teaches a γ9δ2T-cell receptor with first and second polypeptides, namely γ9TCR and δ2TCR chains. Kuball (397) further teaches all of the sequences that contain the γ9-CDR3 and δ2-CDR regions recited in claim 5 of the instant application with 100% sequence similarity (see claim 24 and [0084]).
With regard to claim 6 of the instant application, Kuball (397) claims the use of tumor-reactive αβT-cells that express an exogenous γ9δ2T-cell receptor of a functional fragment thereof (see claims 17 and 20).
With regard to claims 7-10, Kuball (397) teaches a T-cell receptor or fragment thereof with two polypeptides, γ9 and δ2 polypeptide chains, and Kuball (397) teaches all of the SEQ ID numbers of the instant application. As such, Kuball (397) teaches the two polypeptide chains, γ9 and δ2, chains of claims 7-10 with at least 95% sequence similarity (see claim 24).With regard to claim 11 of the instant application, Kuball (397) claims that the composition can be administered to the subject intravenously (see claim 20).
With regard to claims 12-14, these claims are intended result claims, which only limit the process where the clause gives meaning and purpose to the manipulative steps. With regard to claim 12, Kuball (397) teaches administering compositions with 100% sequence similarity in the same manner to the subjects (see claims 17 and 20). Here, a person of ordinary skill in the art would expect to see the same results, reduction in the number of ovarian cancer cells, seeing as they employ the same method with the same compositions and have the previously established motivation to treat ovarian cancer. Similarly, with regard to claims 13 and 14, cytotoxicity to ovarian cancer cells (claim 13) and reduction of ovarian cancer cell growth (claim 14) are necessarily implied in the invention claimed by Kuball (397) because Kuball (397) has a previously established motivation to treat the same disease with the same method and the same compositions. One of ordinary skill in the art would therefore expect the same results, cytotoxicity for ovarian cancer cells and reduction in ovarian cancer growth.
With regard to claims 15 and 19 of the instant application Kuball (397) teaches the use of their claimed composition with an additional anti-cancer agent in the form of a preferred embodiment in the specification (see [0078]). Namely, Kuball (397) teaches the use of a chemotherapeutic agent. Although Kuball (397) does not claim the use of the chemotherapeutic agent in combination with the claimed composition, Kuball (397) does teach an explicit motivation or suggestion to do so by discussing it as an effective means for delivering cancer treatment in a preferred embodiment. Given this motivation, it would have been obvious to one of ordinary skill in the art prior to the effective filing date to use the claimed composition recited in Kuball (397) in combination with a chemotherapeutic agent.
Claims 1, 15-18 and 20 are rejected on the ground of non-provisional nonstatutory double patenting as being unpatentable over claims 1 of U.S. Patent No. 11686724 in view Kuball et al. US 2019/0169260).
Kuball (397), claims a method of treating cancer comprising administering to a subject an engineered αβ T-cell that expresses an exogenous γ9δ2T-cell receptor (see claim 17). Kuball (397) further claims the composition for treating solid cancer cells, including renal cell carcinoma, myeloma, leukemia, head and neck cancer, and colon cancer, but Kuball (397) does not claim the use of the composition for treating ovarian cancer (see claim 5 and [0122]).
Kuball (260) teaches a polypeptide composition with a γδT-cell receptor to treat cancer (see claim 64). Kuball (260) teaches a very similar method as compared to Kuball (397) insofar as Kuball (260) uses αβ T-cells engineered to express the γδT-cell receptor to treat cancers, including ovarian cancer, head and neck cancer, breast cancer, cervical cancer, and many more (see [0078] and claims 25 and 30).
Regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Kuball (397) as taught by Kuball (260) to treat ovarian cancer. One would be motivated to use the method of Kuball (397) to treat ovarian cancer with a reasonable expectation of success because the types of cancers taught in the two references overlap. As mentioned above, both references teach methods for treating cancers of the head, neck, breast, but Kuball (260) further teaches that the method can treat ovarian cancer. Recognizing that the references use the same TCR for the treatment of several of the same cancers and that Kuball (260) expressly suggests treating ovarian cancer, a skilled artisan would have been motivated to use Kuball (397)’s engineered immune responsive cells to treat ovarian cancer.
With regard to claims 15 and 19 of the instant application Kuball (397) teaches the use of their claimed composition with an additional anti-cancer agent in the form of a preferred embodiment in the specification (see [0078]). Namely, Kuball (397) teaches the use of a chemotherapeutic agent. Although Kuball (397) does not claim the use of the chemotherapeutic agent in combination with the claimed composition, Kuball (397) does teach an explicit motivation to do so by discussing it as an effective means for delivering cancer treatment in a preferred embodiment (see [0078]). Given this motivation, it would have been obvious to one of ordinary skill in the art prior to the effective filing date to use the claimed composition recited in Kuball (397) in combination with a chemotherapeutic agent.
With regard to claims 16-18, Kuball (397) claims a method of treating cancer comprising administering an engineered αβ T-cell that expresses exogenous γ9δ2T-cell receptor in claim 17 of their application. As discussed above, Kuball (397) does not claim administering to the subject an additional anti-cancer therapy, but Kuball (397) does teach a motivation for using the composition with an additional anti-cancer agent, specifically a chemotherapeutic, in the form of a preferred embodiment in the specification (see [0078]). Kuball (397) does not, however, expressly claim or recite the timing of the use of this additional agent with respect to the claimed composition.
As discussed above, Kuball (260) teaches a polypeptide composition with a γ9δ2T-cell receptor or fragment thereof to treat cancer, and Kuball (260) teaches that this composition can be administered before, concurrent with, or after the use of anti-cancer treatments like chemotherapy or radiation treatment (see [0007] and [0123]). Given the established rationale for combining the references Kuball (397) and Kuball (260), namely the overlap in cancer targets and treatment methods, it would have been obvious to one of ordinary skill prior to the effective filing date of the instant application to use additional anti-cancer therapies like radiation and chemotherapy before, concurrent with, or after treatment with the claimed composition of Kuball (397). With regard to claim 20, Kuball (397) claims a method of treating cancer in a subject, but it does not specify whether that subject can be human (see claim 17). Kuball (260) does, however, teach a composition for treating cancer in human subjects (see claim 1). Again, given the rationale above, a person of ordinary skill in the art would have recognized the claimed invention could be applied to humans with a reasonable expectation of success.
Summary
Claims 1-20 are rejected under 35 U.S.C. 103. Claims 1-20 are rejected on the ground of nonstatutory double patenting.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brendan P Oliss whose telephone number is (571)272-6347. The examiner can normally be reached Monday - Thursday 8 am – 6 pm.
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/BRENDAN PATRICK NOONAN OLISS/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658