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 and remarks filed on 07/01/2026 are acknowledged.
Claims 1, 8, 10, 12-13, 16-18, 20, 23-25, 29 and 32-37 are pending.
3. Applicant's election with traverse of the invention of Group III in the reply filed on 07/01/2026 is acknowledged.
Applicant traverses the restriction requirement between Groups III and IV. In the interest of compact prosecution, the restriction requirement between Groups III and IV is withdrawn.
In view of the withdrawal of the restriction requirement as to the rejoined inventions, Applicant is advised that if claims directed to any of the rejoined inventions are presented in a continuation or divisional application, such claims may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Applicant further elected, without traverse, the Species of TIM-3. Species election requirement is rendered moot by Applicant’s amendment.
4. Claims 17-18, 20 and 33-37 are withdrawn from further consideration by the Examiner under 37 C.F.R. § 1.142(b) as being drawn to nonelected inventions.
Claims 1, 8, 10, 12-13, 16, 23-25, 29 and 32 are presently under consideration, to the extent that they read on the elected invention
5. Claim 8 is objected to because it recites the subject matter of nonelected invention(s) which is/are not under consideration in the present application. Applicant is required to cancel the non-elected inventions.
6. Claim 10 is objected to because of an apparent typographical error in the phrase “wherein a combination … are administered,” where it appears that “wherein a combination … is administered” was intended. Appropriate correction or clarification is required.
7. Applicant is invited to consider whether claims 8 and 10 are redundant, in view of withdrawal from consideration of the subject matter of non-elected inventions.
8. The following is a quotation of 35 U.S.C. 112(b):
(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.
9. Claims 8 and 25 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 8 is indefinite as being in improper Markush format. The Office recommends the use of the phrase "selected from the group consisting of ..." with the use of the conjunction "and" rather than "or" in listing the species. See MPEP 803.02.
(ii) Claim 25 is indefinite, because the recitation of “the step of agent administration” lacks proper antecedent basis in the base claims.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
10. The following is a quotation 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.
11. Claims 13, 16 and 25 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for the claimed method wherein:
(i) the antibody or antigen binding fragment thereof is not conjugated to a cytotoxic agent, a toxin, or a radioactive isotope, and
(ii) the step of immunodepletion is a transient immunodepletion;
does not reasonably provide enablement for the claimed method wherein:
(i) the antibody or antigen binding fragment thereof is conjugated to a cytotoxic agent, a toxin, or a radioactive isotope, or
(ii) the step of immunodepletion is a complete immunodepletion.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in 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, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
Claims 13 and 16 are directed to a method of treating a hematologic cancer comprising administering a combination of an inhibitor of PD-1 and an inhibitor of TIM-3, wherein the inhibitor is an antibody or an antigen binding fragment thereof, wherein said antibody or antigen binding fragment thereof is conjugated to a cytotoxic agent, a toxin, or a radioactive isotope.
Claim 25 is directed to a method of treating a hematologic cancer comprising administering an inhibitor of PD-1 and an inhibitor of TIM-3, and further comprising a step of complete lymphodepletion.
The specification discloses at page 105 a working example demonstrating that a relatively large percentage of T cells of myeloma bearing mice co-express inhibitory checkpoint proteins PD-1 and TIM-3, among others, and proposes a hypothesis that the anti-myeloma effect of transient lymphodepletion and PD-1 blockade would be increased by blocking other immune checkpoint protein interactions. Working examples described at pages 107-108 demonstrate that blocking PD-L1 in combination with TIM-3 after lymphodepleting whole body irradiation synergistically increased frequencies of tumor-reactive T cells, and improved survival of myeloma bearing mice.
At page 109 of the specification, a model of combined immune checkpoint blockade and lymphodepleting whole body irradiation is proposed, as illustrated in Figure 14. According to the model, in hematologic cancers dysfunctional antigen-activated T cells (e.g. CD4+ and CD8+ T cells) are unable to kill cancer cells. Lymphopenia-induced T cell proliferation allows for reactivation of those T cells. For reactivated T cells to remain functional and kill cancer cells, immune checkpoint proteins must be blocked.
Accordingly, functional T cells must be present in the subject for the claimed method to achieve the desired result. The function of the anti-PD-1 and anti-TIM-3 antibodies is to block the negative signals to the T cells, so that the latter retain their activity against cancer cells.
Therefore, as one of skill in the art would readily understand, if anti-PD-1 and/or anti-TIM-3 antibody conjugated to a cytotoxic agent is used in the claimed method, the antibody would kill PD-1 and/or TIM-3 expressing T cells rather than activate them, thereby preventing the subject from mounting an effective immune response against cancer cells. Likewise, if complete lymphodepletion is performed as recited in claim 25, the subject would not have any viable T cells. Complete lymphodepletion is lethal to the subject in the absence of additional steps such as bone marrow transplantation, which are not recited in the instant claims. Accordingly, the skilled artisan would reasonably conclude that experimentation aimed at developing a method of treating hematologic cancer as recited in claims 13, 16 and 25 would be unsuccessful, and as such unnecessary, improper, and undue.
12. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
13. Claims 1, 8, 10, 12-13, 16, 23-25, 29 and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 10570204.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by or obvious over the claims of US ‘204, optionally as evidenced by Topalian et al. (2012, cited on IDS) and Brahmer et al. (2012).
The latter are directed to a method of treating a subject afflicted with a hematologic cancer, comprising administering to the subject a therapeutically effective amount of a bispecific or multispecific antibody, or antigen-binding fragment thereof, selective for PD-L1 and TIM-3 (claim 1).
A person of skill in the art would have been aware that both PD-1 inhibitors and PD-L1 inhibitors elicit anti-tumor activity primarily by inhibiting binding of PD-L1 to PD-1, and that anti-PD-1 antibodies and anti-PD-L1 antibodies have very similar clinical profile (e.g. described by Topalian 2012 and Brahmer 2012). Therefore, a skilled artisan would have at once envisaged treatment with anti-PD-1 and anti-TIM-3 antibodies in view of treatment with anti-PD-L1 and anti-TIM-3 antibodies as recited in US ‘204. Alternatively, treatment with anti-PD-1 and anti-TIM-3 antibodies would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention in view of treatment with anti-PD-L1 and anti-TIM-3 antibodies as recited in US ‘204.
The limitations of instant claims 8, 10, 12-13, 16, 23-25, 29 and 32 are recited in US ‘204 claims 2-65.
The present application was filed as a Divisional of USSN 16724759, which was filed as a Divisional of USSN 15024396, now US ‘204. Restriction requirements issued during prosecution of each of USSN 15024396 and USSN 16724759 listed methods of treatment comprising administering PD-1 inhibitors and PD-L1 inhibitors in the same group. Accordingly, prohibition of nonstatutory double patenting rejections under 35 U.S.C. 121 does not apply to the present claims, because the present application is not a divisional application “filed as a result of” a restriction requirement.
14. Claims 1, 8, 10, 12-13, 16, 23-25, 29 and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of each of U.S. Patents listed below. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by or obvious over the claims of each of the listed patents, which recite methods of treating hematologic cancer comprising administering to the subject an inhibitor of PD-1 or PD-L1 and an inhibitor of TIM-3:
US Patent No. Exemplary Claims
12630633 1, 2, 6, 36
10981990 1-3, 7-11
10851165 1, 10, 11, 22, 74
10703819 1, 4, 5, 8-11
9683048 5, 10, 14, 18, 29-31
9605070 1, 4-10
15. Claims 1, 8, 10, 12-13, 16, 23-25, 29 and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of each of copending applications listed below. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by or obvious over the claims of each of the listed copending applications, which recite methods of treating hematologic cancer comprising administering to the subject an inhibitor of PD-1 or PD-L1 and an inhibitor of TIM-3:
USSN PG Pub. No. Exemplary Claims
18/980647 20250213684 2, 8, 36, 37, 45
18/392954 20240343808 142, 144, 147-149, 158, 160
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
16. The following US Patents and/or copending US applications share a coinventor and/or an assignee with the present application, and disclose and/or claim subject matter similar to that of the present claims, but do not contain patented or currently pending claims which would anticipate or make obvious the presently claimed invention:
USSN PG Pub. No. US Patent No.
17/104983 20210220404
19/262665 20260034195
19/348293 20260021178
11708412
11939389
17. Conclusion: no claim is allowed.
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 9 AM - 5:30 PM.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644
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