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 05/20/2025 are acknowledged.
Claims 154-177 are pending.
3. Applicant’s election without traverse of the invention of Group I (claims 154-158, and new claims 168-177) in the reply filed on 05/20/2025 is acknowledged.
Claims 159-167 are withdrawn from further consideration by the Examiner under 37 C.F.R. § 1.142(b) as being drawn to nonelected inventions.
Claims 154-158 and 168-177 are presently under consideration.
4. Applicant’s attention is drawn to the following apparent terminological inconsistency in claim 168 (emphasis added):
“anti-ICOS antibody comprises a heavy chain amino acid sequence identical to the amino acid sequence of SEQ ID NO: 410,” vs
“anti-ICOS antibody comprises an [light chain?] amino acid sequence identical to the amino acid sequence of SEQ ID NO: 417.”
5. 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.
6. Claims 154-158 and 168-177 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 154 is indefinite in the recitation of a method of “treating a patient,” because the patient population is unknown. The limitation specifying that the treatment is administered to “a patient who has an increased level of ICOS-positive regulatory T cells following treatment with another therapeutic agent” does not define a population of “patients,” because “increased level of ICOS-positive regulatory T cells” is not a disease.
(ii) Claim 154 is further indefinite in the recitation of an “increased” level of ICOS-positive regulatory T cells, because neither the baseline level of ICOS-positive regulatory T cells nor the requisite degree or level of “Increase” are defined.
(iii) Claims 155-158 and 168-177 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
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.
7. 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.
8. Claims 154-158 and 168-177 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contain(s) subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not provide a sufficient enabling description of a method of treating “a patient who has an increased level of ICOS-positive regulatory T cells following treatment with another therapeutic agent.”
The specification does not enable one of skill in the art to make and use the invention as claimed without undue experimentation. 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.
The claims are directed to a method of treating a patient who has an increased (to an unknown degree from an unknown base level – see section 6 above) level of ICOS-positive regulatory T cells (ICOS+ Tregs). Since the ICOS+ Treg level is not tied to the nature of the disease the patient is suffering from, the claims encompass treatment of patients suffering from any disease whatsoever. The stipulation that the patient has increased ICOS+ Treg level “following treatment with another therapeutic agent” does not limit the scope of the claims in any way, because any adult subject can be assumed to have been treated with some therapeutic agent at some prior point in their life.
The specification contains multiple references to treatment of cancer, but does not appear to provide guidance to allow a person of skill in the art to identify diseases treatable by the claimed method. The state of prior art does not appear to include the knowledge of diseases treatable with anti-ICOS antibodies (other than potentially cancer), or of diseases associated with increased levels of ICOS+ Tregs, but it does include appreciation for the positive effects of therapeutically increasing Treg levels, such as in treating autoimmune diseases (e.g. Spence et al. 2015, e.g. p. 14).
In the absence of sufficient guidance, direction, working examples, or prior art knowledge regarding therapeutic application of anti-ICOS antibodies in the context of instant claims, the outcomes of the claimed treatment are completely unpredictable, and may likely be negative in certain conditions such as autoimmunity.
Given the level of unpredictability, as well as the resource-intensive nature and the risks of the required experimentation, a skilled artisan would reasonably conclude that such experimentation would entail an inordinate amount of trial and error, and therefore would be unnecessarily, and improperly, extensive and undue.
9. 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(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.
10. Claims 154-157 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Faget et al. (US 20140086923).
Faget at [0190] provides the following teachings:
“As shown in Example 6, treatment of an established murine model of mammary tumor with a surrogate neutralizing rat anti murine ICOS antibody (17G9, IgG2b), reduces tumor progression, reenforcing the potential of treatment with anti-ICOS neutralizing antibodies of the invention to favor of tumor regression in the subpopulation of patients with high ICOS.sup.+ Treg detection in their primary breast tumor.” Accordingly, Faget teaches a method of treating breast cancer comprising administering an anti-ICOS antibody to patients who have an increased level of ICOS-positive regulatory T cells.
The standard clinical practice is to administer new experimental therapies only to patients who have not responded to, or progressed after, the standard-of-care first line treatment. Therefore, patients eligible for anti-ICOS treatment would have been previously treated with another therapeutic agent. As such, the method taught by Faget is within the scope of instant claim 154.
Faget further teaches that ani-ICOS antibodies of human IgG1 class, and/or comprising human heavy and light chain constant regions [0161]. Human IgG1 antibodies comprise an Fc effector positive constant region, as one of skill in the art would be aware. Faget further teaches that it is desirable to modify the ani-ICOS antibody of the invention so as to enhance ADCC and/or CDC function [0185]. Accordingly, Faget teaches all of the limitations of claims 154-157, and as such anticipates these claims.
11. 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 of this title, 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.
12. Claims 154 and 158 are rejected under 35 U.S.C. 103 as being unpatentable over Faget et al. (US 20140086923) in view of Coyle et al. (US 20080279851).
As noted in section 10 above, Faget teaches a method within the scope of instant claim 154, wherein the anti-ICOS antibody has enhanced ADCC and/or CDC functions. Faget further teaches that anti-ICOS antibodies can be modified to obtain antibody with desirable characteristics, in particular by altering N-linked glycosylation patterns (e.g. [0172], [0182], [0185]).
Although Faget does not specifically exemplify afucosylation as a way of enhancing ADCC, afucosylation was known and routinely used in the art for this purpose, as taught e.g. by Coyle ([0286], [0608], [0612] ), who produced afucosylated anti-ICOS antibody (IC9G1-aFuc) with increased ADCC [0626], which effectively depleted ICOS+ T cells in vivo (e.g. [0040], and Fig. 11).
Based on these teachings, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use afucosylation for making anti-ICOS antibodies with enhanced effector functions, both the motivation and the expectation of success being provided by the teachings of the references.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
13. 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.
14. Claims 154-158 and 173-177 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 9957323 (IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of US ‘323, as evidenced by Giraldo et al. (2017), or obvious over the claims of US ‘323 in view of Coyle et al. (US 20080279851).
US ‘323 claims an anti-ICOS antibody comprising SEQ ID NOS: 408 and 415 (claim 1), which are identical to instant SEQ ID NOS: 408 and 415, respectively (see score). The antibody comprises an effector enabled human IgG1 constant region (claim 7), and may be multispecific (claim 8). US ‘323 further claims a method of treating cancer, such as renal cell cancer, comprising administering the antibody (claims 15 and 16).
Giraldo teaches an increased level of ICOS-positive regulatory T cells in renal cell cancer (e.g. the Abstract), which is therefore inherent in renal cell cancer patients treated by the method claimed in US ‘323. Patients eligible for anti-ICOS treatment would have been previously treated with another therapeutic agent, as explained in section 10 above.
Coyle provides the motivation and expectation of success to enhance effector function of anti-ICOS antibodies by afucosylation, as explained in section 12 above.
Claim 177 is included in the rejection, because selective depletion of pathogenic cells with cytotoxic immunoconjugates was routine in the art before the effective filing date of the claimed invention, and as such would be at once envisaged by those skilled in the art.
15. Claims 154-158 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 10604576.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of US ‘574, as evidenced by Giraldo et al. (2017), or obvious over the claims of US ‘574 in view of Coyle et al. (US 20080279851).
US ‘574 claims are directed to a method of treating a tumor such as renal cell cancer comprising administering an antibody that specifically binds to ICOS (claims 1 and 5-8), and anticipate or make obvious the instant claims for the same reasons as expounded in section 14 above.
16. Claims 168-177 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11858996 (IDS).
Claims 1-21 of US ‘996 are directed to the same antibody as recited in instant claims 168-177, and claims 22-29 of US ‘996 are directed to methods of treating cancer such as renal cell cancer comprising administering the antibody, and anticipate or make obvious the instant claims, as evidenced by Giraldo et al. (2017) and in view of Coyle et al. (US 20080279851), for the same reasons as expounded in section 14 above.
Prohibition of nonstatutory double patenting rejections under 35 U.S.C. 121 is deemed inapplicable to claims 168-177, for the following reasons:
The present application was filed on 02/07/2019 as a Divisional of USSN 16323980, issued on 01/02/2024 as US ‘996. Claims 1-21 of US ‘996 are directed to the same antibody as recited in instant claims 168-177, and claims 22-29 of US ‘996 are directed to methods of treating cancer comprising administering the antibody.
A Requirement for Restriction/Election issued on 09/20/2021 during prosecution of USSN ‘980 identified the following two inventions, among others:
I. Claims 17, 19-20, 22, 25, 29-32, 38, 40-41, 114-117 and 119(d), drawn to an anti-ICOS antibody comprising variable domains or CDRs of STIM003, and to methods comprising administering the antibody to a patient.
ll. Claims 63 and 68-69, drawn to a method comprising administering any anti- ICOS antibody to a patient.
Applicant elected the invention of Group I for prosecution in USSN ‘980 in the reply dated 12/20/2021.
Instant claim 154 is recited identically to claim 63 of USSN ‘980, and instant claims 154-158 are consonant with the non-elected invention of Group II, defined as “a method comprising administering any anti-ICOS antibody to a patient.”
Instant claims 168-177 are directed to methods comprising administering to a patient an anti-ICOS antibody comprising variable domains of STIM003 (i.e. SEQ ID NOS: 408 and 415), and as such are consonant with the invention of Group I, elected by Applicant for prosecution in USSN ‘980 and issued as U.S. Patent No. 11858996. Consequently, prohibition of nonstatutory double patenting rejections under 35 U.S.C. 121 does not apply to instant claims 168-177.
17. Claims 154-158 and 173-177 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11629189 (IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over the claims of US ‘189 in view of Faget et al. (US 20140086923) and Coyle et al. (US 20080279851).
US ‘189 claims an anti-ICOS antibody comprising the same VH and VL sequences as recited in instant claim 173 (claims 16, 20, and 24).
Faget, described in section 10 above, provides motivation and expectation of success in using anti-ICOS antibodies for treating breast cancer, in particular characterized by increased levels of ICOS+ Tregs [0190]. Coyle, described in section 12 above, provides motivation and expectation of success in using afucosylated anti-ICOS antibodies for treating cancer (e.g. [0040], [0626]). The present invention would have been obvious over the claims of US ‘189 in view of the teachings of Faget and Coyle, for the reasons articulated in sections 10 and 12 above.
18. Claims 154-158 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of the following copending applications (all cited on IDS):
USSN 17/921822 (PG Pub. No. 20230176060),
USSN 18/616452 (PG Pub. No. 20240343810), and
USSN 16/955197 (PG Pub. No. 20200317786).
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 these copending applications, which recite methods of treating cancer comprising administering anti-ICOS antibodies, for the same reasons as addressed above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
19. Claims 154-158 and 168-177 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of the following copending applications:
USSN 18/510228 (PG Pub. No. 20240190964),
USSN 17/747886 (PG Pub. No. 20220396623, IDS),
USSN 18/174925 (PG Pub. No. 20230348601, IDS), and
USSN 16/471161 (PG Pub. No. 20200190191, IDS).
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 these copending applications, which recite methods of treating cancer comprising administering the same anti-ICOS antibodies as recited in instant claims, for the same reasons as addressed above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
20. The following US Patents and/or copending applications share a coinventor and/or an assignee with the present application, and disclose the 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:
US Patent No. 11440960, 11773175, 11779604, 11965026 (IDS), and 12209128.
21. The following prior art is cited of record but not presently relied upon:
Sazinsky et al. (US 10023635) teaches and claims methods of treating cancer with anti-ICOS antibodies (e.g. claims 22-25).
Faget et al. (2012) ICOS-ligand expression on plasmacytoid dendritic cells supports breast cancer progression by promoting the accumulation of immunosuppressive CD4+ T cells. Cancer Res. 72: 6130–6141.
Nagase et al. (2017) ICOS Foxp3 TILs in gastric cancer are prognostic markers and effector regulatory T cells associated with Helicobacter pylori. Int J Cancer. 140: 686–695.
22. Conclusion: no claim is allowed.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644