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 .
Claim Status
Applicant’s reply filed on 08/07/2025 is acknowledged. Claims 25, 149, 166, 170, 173, and 176 have been amended. Claims 25, 149-151, 154, 159-160, 162, 165-167, and 169-178 are pending. Claims 159, 170-172, and 176-178 have been withdrawn from consideration as being drawn to nonelected subject matter.
Claims 25, 149-151, 154, 160, 162, 165-167, 169, and 173-175 are under examination.
Information Disclosure Statement
The information disclosure statement filed 08/07/2025 has been considered and an initialed copy has been enclosed herewith.
Rejections Withdrawn
The rejection of claim 165 under 35 U.S.C. 112(b) is withdrawn in view of convincing arguments in the reply filed 08/07/2025.
The rejection of claims 25, 149-151, 154, 160, 162, 165-167, 169, and 173-175 under 35 U.S.C. 112(a) is withdrawn in view of amendments filed 08/07/2025.
Rejections Maintained
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.
Claims 25, 149-151, 154, 160, 162, 165-167, 169, and 173-175 are rejected under 35 U.S.C. 103 as being unpatentable over Johnston (US 2019/0330364 A1, published 10/31/2019, effectively filed 01/11/2017, PTO-892 05/31/2024) in view of Tinoco (Immunity. 2016 May 17;44(5):1190-203) as evidenced by Huo (Trends Cardiovasc Med. 2009 May;19(4):140-5, PTO-892 11/29/2024) and Tchernychev (Cell Biol. 2003 Dec 8;163(5):1145-55, PTO-892 11/29/2024) .
The disclosure of Johnston is directed to methods of identifying and using PSGL-1 antagonists and provides antibodies that bind PSGL-1 (see abstract). Of note, the instant disclosure uses the name SELPLG (selectin P ligand), but the alias PSGL-1 (P-selectin glycoprotein ligand-1) is more commonly used in the literature and will be used herein to match the prior art cited.
Regarding claims 25 and 173 pertaining to a method of increasing an inflammatory phenotype of monocytes and/or macrophages in a subject (claim 25) and a method of sensitizing cancer cells in a subject to cytotoxic CD8+ T cell mediated killing and/or immune checkpoint therapy (claim 173), comprising administering to a subject an antibody or antigen-binding fragment thereof that downregulates the copy number, amount and/or activity of at least one target listed in claim 25 in monocytes/or macrophages, Johnston discloses the administration of a PSGL-1 antagonist to a subject having cancer ([0113], Lines 1-3).
Regarding claim 149, wherein the antibody or antigen-binding fragment thereof according to the method of claim 25 is in a pharmaceutically acceptable formulation, Johnston discloses that the PSGL-1 antagonist is provided in formation with pharmaceutically acceptable carriers ([0102], Lines 1-3).
Regarding claims 150 and 175 wherein the monocytes and/or macrophages having a modulated inflammatory phenotype according to the method of claim 1 exhibit the phenotypes as listed in claim 150, administration of the PSGL-1 antagonist antibody of Johnston would necessarily result in the claimed phenotype as evidenced by the instant specification which teaches that downregulation of the targets of Table 1 by agents such as antibodies is associated with and results in an increased inflammatory phenotype (specification, Page 71, Lines 22-25).
Regarding claim 151, wherein the cells and/or macrophages comprise Type 1 macrophages, M1 macrophages, Type 2 macrophages, M2 macrophages, M2c macrophages, M2d macrophages, tumor-associated macrophages (TAM), CD11b+ cells, CD14+ cells, and/or CD11b+/CD14+ cells Johnston discloses the use of the PSGL-1 antagonist antibody in methods for treating cancer comprising administering the antagonist to a subject ([0010], Lines 1-4) and contemplates various routes of administration including subcutaneously and intravenously ([0101], Lines 1-3). Administration of the antagonist to a subject in vivo would necessarily bring the antagonist into contact with the claimed cell types, including the elected M2 macrophage population, as they all occur within the organism.
Regarding claim 154, wherein the method according to claim 25 is occurring in the context of the list of disclosed cancer types and in particular, melanoma as elected, Johnston discloses methods of treating cancer comprising administering PSGL-1 antagonist to a subject with cancer ([0098], Lines 1-3) and discloses melanoma as an exemplary cancer ([0098], Line 21).
Regarding claim 160, wherein the monocytes and/or macrophages are comprised within a tissue microenvironment, the claims are interpreted as occurring in vivo as opposed to in culture and Johnston discloses the administration of the PSGL-1 antagonist to a subject having cancer ([0113], Lines 1-3).
Regarding claim 162, wherein the subject according to claim 25 is a human, Johnston discloses the method of administration of the PSGL-1 antagonist to a subject having cancer ([0113], Lines 1-3) and defines “subject” as a human ([0077], Lines 1-3).
Regarding claim 165, wherein the pharmaceutically acceptable formulation according to the method of claim 149 is substantially endotoxin-free and/or has less than about 1 EU/mg protein, Johnston teaches that the pharmaceutically acceptable carrier of the disclosure refers to a non-toxic solid, semisolid, or liquid filler, diluent, encapsulating material, formulation auxiliary, or carrier ([0092], Lines 1-3), which broadly, but reasonably indicates that the formulation would be substantially endotoxin-free.
Regarding claim 166, wherein the macrophages according to the method of claim 151 are determined to express SELPLG (PSGL-1), the macrophages would necessarily express PSGL-1 as evidenced by Huo who teaches that PSGL-1 is constitutively expressed on all leukocytes (Pg. 2, Full paragraph 2, Line1) and Tchernychev who teaches specifically that macrophages are known to express PSGL-1 (Abstract, Lines 1-3 and Fig. 4A, green stain).
Regarding claim 167, wherein the macrophages according to the method of claim 151 are TAMs and or M2 macrophages, Johnston teaches a method for treating or preventing cancer comprising administering an effective amount of PSGL-1 antagonist to a subject in need of such treatment ([0096], Lines 1-4). Administration of the antagonist to a subject in vivo would necessarily bring the antagonist into contact with the claimed cell types, including the elected M2 macrophage population, as they all occur within the organism.,
Johnston does not teach administering PSGL-1 antagonists to a subject who is afflicted with cancer and is resistant to or progressed on an immune checkpoint inhibitor, wherein the immune checkpoint is an anti-PD1 antibody
This deficiency is taught by Tinoco.
The disclosure of Tinoco is directed to investigating the function of PSGL-1 and the effect of PSGL-1 deficiency in the context of cancer (see Abstract). Tinoco teaches that PSGL-1 deficiency results in PD-1 downregulation, improved T cell responses, and decreased tumor growth in melanoma models (see Abstract and Pg. 1198, Left column, Full paragraph 1, Lines 6-17, Fig. 7A)
Regarding the methods of claims 25 and 173 wherein the subject is afflicted with a cancer, and wherein the subject is resistant to or progressed on an immune checkpoint inhibitor, Tinoco teaches that multiple inhibitory receptors are impacted by PSGL-1, and PSGL-1 could be a target for which a functional blockade could generally improve T cell responses in many clinical settings, including with tumors that are unresponsive to checkpoint inhibition (emphasis added, Pg. 1201, Left column, Fill paragraph 1, Lines 6-11).
Regarding claims 169 and 174, wherein the immune checkpoint inhibitor of the methods of claims 25 and 173 is an anti-PD1 antibody, Tinoco teaches that PSGL-1 deficiency results in PD-1 downregulation and thus PSGL-1 inhibition would be suited for the treatment of patient resistant to anti-PD-1 treatment (Pg. 1190, Summary, Lines 15-18 and Fig. 2G).
It would have been obvious to one having ordinary skill in the art to administer the anti-PSGL-1 antibody of Johnston to patients who are resistant to checkpoint inhibition and specifically anti-PD-1 checkpoint inhibition as taught by Tinoco. One would have been motivated to do so because Tinoco teaches PSGL-1 deficiency leads to PD-1 downregulation, improves T cell responses, and improves tumor control. Tinoco contemplates PSGL-1 as a therapeutic target for tumors that are unresponsive to inhibition of other checkpoints. There would be an expectation of success in administering the anti-PSGL-1 antibody to subjects resistant to an immune checkpoint inhibitor because Johnston and Tinoco both teach that PSGL-1 inhibition or deficiency controls tumor growth.
Response to Applicant’s Arguments
Applicant's arguments filed 08/07/2025 have been fully considered but they are not persuasive.
The applicant argues that none of the cited references teach or suggest methods for increasing an inflammatory phenotype of monocytes and/or macrophages in a subject afflicted with a cancer, wherein the subject is resistant to or progressed on an immune checkpoint inhibitor, as recited in claim 25. (Remarks, Pg. 11) The applicant further argues that Tinoco does not provide a reasonable expectation of success for performing the method of the instant invention because the disclosure states that that "PSGL-1 could be a target for which a functional blockade could generally improve T cell responses in many clinical settings, including with tumors that are unresponsive to checkpoint inhibition" (emphasis added, Remarks, Pg. 11)
In response, it is clear that Tinoco provides a motivation for administration of a PSGL-1 antagonist to a subject that is unresponsive to checkpoint inhibition. As to whether Tinoco provides a reasonable expectation of success in performing this method, Tinoco provides evidence in a melanoma model that Selplg-/- mice had better tumor control than WT mice as evidenced by slower tumor growth (Fig. 7A). Importantly, PD-1 expression on both CD4+ and CD8+ T cells in Selplg-/- mice was lower than it was on WT cells (Figures 7C and 7E). Tinoco does therefore provide a reasonable expectation that administration of PSGL-1 antagonist could improve outcomes in a subject resistant or progressed on an immune checkpoint inhibitor.
Addressing the argument that none of references teach that the method increases the inflammatory phenotype of monocytes and/or macrophages, this is an inherent property of SELPLG antagonism as evidenced by the instant disclosure and is thus only an intended result of the method. The two limitations from claim 25 that have patentable weight are: (1) the population that is being treated, namely, a subject resistant or progressed on an immune checkpoint inhibitor and (2) the active method step, namely, administration of an antibody or antigen-binding fragment thereof to said subject. To this end, the combined teachings of Johnston and Tinoco do indeed provide both the motivation and reasonable expectation of administering an anti-SELPLG antagonist antibody to a subject afflicted with cancer that is resistant to or progressed on an immune checkpoint inhibitor. For these reasons the 35 U.S.C. 103 rejections are maintained.
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 25, 149-151, 154, 160, 162, 165-167, 169, and 173-175 remain/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 118-148 of copending Application No. 17/615,863 in view of Johnston (US 2019/0330364 A1, published 10/31/2019, effectively filed 01/11/2017, PTO-892 05/31/2024) and Tinoco (Immunity. 2016 May 17;44(5):1190-203) as evidenced by Huo (Trends Cardiovasc Med. 2009 May;19(4):140-5, PTO-892 11/29/2024) and Tchernychev (Cell Biol. 2003 Dec 8;163(5):1145-55, PTO-892 11/29/2024).
Regarding instant claims 25 and 173 pertaining to a method of increasing an inflammatory phenotype of monocytes and/or macrophages in a subject (claim 25) and a method of sensitizing cancer cells in a subject to cytotoxic CD8+ T cell mediated killing and/or immune checkpoint therapy (claim 173), comprising administering to a subject an antibody or antigen-binding fragment thereof that downregulates the copy number, amount and/or activity of at least one target listed in claim 25 in monocytes/or macrophages, ‘863 claims 118-120 teach a monoclonal antibody that binds PSGL-1 and increased the inflammatory phenotype of myeloid cells. ‘863 claim 146 teaches the modified myeloid cells are comprised within a human tumor model, which broadly, but reasonably anticipates administration of the antibody to as subject.
Regarding instant claim 149, wherein the antibody or antigen-binding fragment thereof according to the method of claim 1 is in a pharmaceutically acceptable formulation, ‘863 claim 147 discloses a pharmaceutical composition comprising the anti-PSGL-1 antibody in a pharmaceutically acceptable carrier.
Regarding instant claims 150 and 175, wherein the monocytes and/or macrophages having a modulated inflammatory phenotype according to the method of claim 1 exhibit one or more of a disclosed list of phenotypes, ‘863 claim 120 discloses that the PSGL-1 antibody modulates the inflammatory phenotype of cells according to measures that are coextensive with those disclosed in the instant claims.
Regarding instant claim 151 wherein the macrophages according to the method of claim 25 comprise one of the cell types disclosed in the claim, ‘863 claims 142 and 143 disclose phenotype modulation by contact with the anti-PSGL-1 antibody in the cell populations as disclosed in the instant claim 151.
Regarding instant claim 160, wherein the monocytes and/or macrophages according to the method of claim 1 are comprised within a tissue microenvironment, ‘863 claim 146 discloses modulation of myeloid cells within a human tumor model or an animal model of cancer, which broadly but reasonable anticipates the limitation wherein the monocytes and/or macrophages are comprised within a tissue microenvironment.
Regarding instant claim 162, wherein the subject according to claim 25 is a human, ‘863 claim 146 discloses modulation of myeloid cells within a human tumor model.
Regarding instant claim 166, wherein the macrophages according to the method of claim 151 are determined to express at least one target selected from the group disclosed in claim 166, ‘863 claim 146 modulation of human or animal macrophages would necessarily express PSGL-1 as evidenced by Huo who teaches that PSGL-1 is constitutively expressed on all leukocytes (Pg. 2, Full paragraph 2, Line1) and Tchernychev who teaches specifically that macrophages are known to express PSGL-1 (Abstract, Lines 1-3 and Fig. 4A, green stain).
Regarding instant claim 167, wherein the macrophages according to the method of claim 155 are TAMs and or M2 macrophages, ‘863 claim 146 modulation of human or animal tumor model would necessarily bring the antagonist into contact with the claimed cell types, including the elected M2 macrophage population, as they all occur within the organism.
Copending ‘863 does not teach (1) administering PSGL-1 antagonists to a subject who is afflicted with cancer and is resistant to or progressed on an immune checkpoint inhibitor, wherein the immune checkpoint is an anti-PD1 antibody, (2) wherein the method according to claims 25 is occurring in the context of the list of disclosed cancer types of instant claim 154, or (3) wherein the pharmaceutically acceptable formulation is substantially endotoxin-free.
These deficiencies are taught by Tinoco and Johnston.
Regarding the methods of instant claims 25 and 173 wherein the subject is afflicted with a cancer, and wherein the subject is resistant to or progressed on an immune checkpoint inhibitor, Tinoco teaches that multiple inhibitory receptors are impacted by PSGL-1, and this receptor could be a target for which a functional blockade could generally improve T cell responses in many clinical settings, including with tumors that are unresponsive to checkpoint inhibition (Pg. 1201, Left column, Fill paragraph 1, Lines 6-11).
Regarding claims 169 and 174, wherein the immune checkpoint inhibitor of the methods of claims 25 and 173 is an anti-PD1 antibody, Tinoco teaches that PSGL-1 deficiency results in PD-1 downregulation and thus PSGL-1 inhibition would be suited for the treatment of patient resistant to anti-PD-1 treatment (Pg. 1190, Summary, Lines 15-18 and Fig. 2G).
Regarding instant claim 154, wherein the method according to claim 25 is occurring in the context of the list of disclosed cancer types, Tinoco investigates the effects of PSGL-1 deficiency in melanoma models (Abstract).
Regarding instant claim 165 wherein the pharmaceutically acceptable formulation according to the method of claim 149 is substantially endotoxin-free, Johnston teaches that the pharmaceutically acceptable carrier of the disclosure refers to a non-toxic solid, semisolid, or liquid filler, diluent, encapsulating material, formulation auxiliary, or carrier ([0092], Lines 1-3), which broadly, but reasonably indicates that the formulation would be substantially endotoxin-free.
It would have been obvious to one having ordinary skill in the art to (1) administer the anti-PSGL-1 antibody of copending ‘863 to a subject who is afflicted with cancer and is resistant to an anti-PD-1 immune checkpoint inhibitor, (2) to administer the anti-PSGL-1 antibody to a subject having melanoma, and (3) to formulate the pharmaceutical composition wherein the formulation is substantially endotoxin-free. One would have been motivated to do so because Tinoco teaches PSGL-1 deficiency leads to PD-1 downregulation, improves T cell responses, and improves tumor control in a melanoma model and Johnston teaches the industry standard non-toxic pharmaceutical formulation. There would be an expectation of success in administering the anti-PSGL-1 antibody to subjects resistant to an immune checkpoint inhibitor because Johnston and Tinoco both teach that PSGL-1 inhibition or deficiency controls tumor growth in a melanoma model.
This is a provisional nonstatutory double patenting rejection.
Response to Applicant’s Arguments
The applicant requests withdrawal of the nonstatutory double patenting rejection for having a later filing date as the instant invention and being the only remaining rejection.
As the 35 U.S.C. 103 rejection is maintained as described above, the nonstatutory double patenting rejection will also be maintained herein.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROL ANN CHASE whose telephone number is (571)270-0934. The examiner can normally be reached Monday-Friday 9:00am-6:00pm.
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/CAROL ANN CHASE/Examiner, Art Unit 1646
/HONG SANG/Primary Examiner, Art Unit 1646
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