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 .
Election/Restrictions
Applicant’s election without traverse of a blocking anti-PD-L1 antibody as the second therapeutic agent in the reply filed on 10/24/2025 is acknowledged.
Claims 11 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/24/2025.
Claims 1-10, 12-22, and 24-25 are examined on the merits in the present Office Action.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Written Description
Claims 1-10, 12-22, and 24-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 does not recite any structural features for the broad genus of anti- SIRPα antibodies correlated with the functional property of binding to the ECD of SIRPα so as to disrupt the SIRPα pathway and treat cancer in a subject.
Claim 13 and 25 recite an anti-SIRPα antibody comprising a means for binding to the ECD of SIRPα and/or a means for disrupting the SIRPa pathway, each of which invokes means-plus-function and is thus limited to structures disclosed in the specification or equivalents thereof. However, the specification does not disclose structural features or other identifying characteristics sufficient to distinguish antibodies that disrupt SIRPα from other ECD-binding antibodies that do not, nor does it establish that the disclosed antibody clones –p84, ED9, SE7C2, and 24AM5-5/SIRP29—known in the art are representative of the full scope of the antibodies encompassed by the claim. In other words, the antibody clones used in the working examples are not expressly described as antibodies of the invention itself.
All claims dependent directly or indirectly from claims 1 and 13 fail to cure the written description deficiencies of these claims and are thus also rejected.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (MPEP 2163).
In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin [e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting at 1171, 25 USPQ2d at 1606). Also see (CAFC 2002). Enzo-Biochem v. Gen-Probe Fiers, 984 F.2d 01-1230.
Claim 1 recites a method for treating cancer in a patient comprising administering to the patient 1) an anti-SIRPα antibody or antigen-binding fragment that specifically binds to the extracellular domain of SIRPα so as to disrupt the SIRPα pathway as a first active agent, and 2) an anti-PD-L1 antibody (elected species) as the second active agent, wherein the cancer is not SIRPα -positive acute myeloid leukemia.
An anti-SIRP alpha compound is defined as a compound that specifically binds to the extracellular domain of SIRP alpha or a compound able to inhibit the expression of the SIRP alpha protein. Such a compound is further able to inhibit the polarization of anti-inflammatory M2-type macrophages and/or favor pro-inflammatory M1-type macrophages (Page 13, Ln. 9 – 13). Exemplary anti-SIRPα compounds capable of binding to the ECD of SIRPα include anti-SIRPα antagonistic antibodies (Page 13, Ln. 17-28). However, the specification does not identify a representative number of species across the claimed genus of anti-SIRPα antibodies nor does it identify any structural features shared by members of the claimed genus correlated with the functional properties of binding to the extracellular domain of SIRPα and blocking the SIRPα pathway.
It is well-known in the art that, in order to bind antigen, a conventional antibody or antigen-binding fragment must have six complementarity defining regions (CDRs) (Janeway, see selection, in particular section 3-6). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chain, and not either alone, that determines the final antigen specificity. As presently written, however, the claims do not recite the amino acid sequences of six non-degenerate CDRs for the genus of anti-SIRPα antibodies correlated with the functional property of binding to the ECD of SIRPα in order to disrupt SIRPα pathway and treat cancer in a subject. While Applicant has provided examples of anti-SIRPα antibodies that bind to the ECD of SIRPα, including –clones p84, SE7C9, SIPR29, and ED9—such disclosure does not adequately represent the structural diversity of the claimed genus of anti-SIRPα antibodies that bind to the ECD in order to block the SIRPα pathway and treat cancer in a subject. In fact, not all anti-SIRPα antibodies that bind to the ECD of SIRPα disrupts the SIRPα pathway. For example, an agonistic anti-SIRPα antibody raised against the ECD of SIRPα that exhibits potent anti-inflammatory effects, including inhibition of monocyte and neutrophil migration into inflamed tissues, has recently been identified (Xie et al, see Abstract and 3rd para on Page 2, Left Column). Such an antibody would not reasonably be expected to treat cancer mediated by the CD47/ SIRPα pathway. Thus, mere binding of an antibody to the SIRPα ECD does not confer SIRPα pathway disruption and anti-cancer activity. However, the specification does not identify any shared structural features among members of the claimed genus that would distinguish antibodies that merely bind to the SIRPα extracellular domain from those that also disrupt the SIRPα pathway and treat cancer in a subject. Without further guidance, artisans would have to engage in additional, unpredictable basic science research to identify anti- SIRPα antibodies that not only bind the SIRPα extracellular domain but also disrupt the SIRPα pathway and treat cancer in a subject.
Claims 2, 3, 5, 7, and 12 (which each depend on claim 1) further recite that the anti-SIRP antibody is administered at a dose that
favors pro-inflammatory M1 type macrophages in a tumor
inhibits differentiation of macrophages into anti-inflammatory M2-type macrophages
favors differentiation of macrophages into pro-inflammatory M1-type macrophages
both (b) and (c); or
increases expression of at least one of the markers CD86 and CCR7 by M1-type macrophages and/or increases the secretion of at least one of the cytokines IL-6, TNFa, IL-12p40, or IL-12 by M1-type macrophages.
The specification teaches that different anti-SIRPα antibodies that bind to the ECD of SIRPα modulate macrophage phenotype and cytokine profiles in different ways. For example, the p84 clone prevented acquisition of the M2 macrophage phenotype induced by IL-4 in vitro in murine macrophages, inhibiting expression of hallmark M2 markers (CD206, CD11b, and PD-L1) (Page 11, Ln. 34-38; Example 1.1, Figure 11).SE7C2 and SIRP29 were found to decrease expression of the M2 marker CD200R, and increase expression of the M1 markers CD80 and IL-6 in human macrophages (Page 12, Ln. 1- 5; Figure 12) as well as iNOS expression in M1 macrophages (Page 10, Ln. 26 – 30; Example 1.2, Figure 4). ED9 was also shown to induce rat M2 macrophages to become pro-inflammatory and secrete inflammatory cytokines, TNF-alpha and IL-6 (Page 7, Ln. 21-28; Page 12, Ln. 12- 16; Example 1.3, Figure 14). However, these disclosed antibodies are not representative of the full scope of the claimed genus because the specification does not establish that binding to the SIRPα extracellular domain predictably results in the claimed functional outcomes relating to macrophage phenotype and cytokine expression.
Claim 13 recites an anti- SIRPα antibody or fragment thereof comprising a “means for binding to the extracellular domain of SIRPα”, wherein the anti- SIRPα antibody or fragment thereof disrupts the SIRPα pathway. The limitation –a means for binding to the extracellular domain of SIRPα – invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, and is therefore limited to the corresponding structures disclosed in the specification and equivalents thereof. The specification functionally defines anti-SIRPα compounds as compounds that bind to the SIRPα ECD and identifies antagonistic anti-SIRPα as exemplary compounds. The specification further discloses the use of certain anti- SIRPα antibodies known in the art (e.g. p84, ED9, SE7C2, and 28AM4-5/SIRP29) that bind to the ECD and disrupt SIRPα signaling. However, the specification does not disclose structural features or other identifying characteristics sufficient to distinguish antibodies that disrupt SIRPα from other ECD-binding antibodies that do not, nor does it establish that the disclosed antibody clones are representative of the full scope of the antibodies encompassed by the claim. In other words, the antibody clones used in the working examples are not expressly described as antibodies of the invention itself. Given that antibodies binding the SIRPα ECD are known to exhibit differing functional activities, such as agonism as discussed above, the specification does not demonstrate possession of the claimed invention across the full scope. Dependent claims 14, 15, 17, 19, and 24 (which each depend on claim 13) further recite functional outcomes relating to macrophage phenotype and cytokine expression but do not cure the written description deficiencies of claim 13; and as stated previously, the specification does not establish that binding to the SIRPα extracellular domain predictably results in any of the claimed functional and therapeutic outcomes (i.e. blocking the SIRPα, promoting M1 macrophage phenotype and cytokine expression, inhibiting M2 macrophage phenotype and cytokine expression, and treating cancer in a subject).
Lastly, claim 25 recites a method for treating cancer comprising administering an anti- SIRPα antibody or fragments thereof comprising means for binding to the ECD of SIRPα and means for disrupting the SIRPα pathway, each of which invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, and are therefore limited to the corresponding structures disclosed in the specification and equivalents thereof. As discussed above with respect to claim 13, the specification does not identify corresponding structure sufficient to support the recited “means for binding to the ECD of SIRPα” or “means for disrupting the SIRPα pathway”. Accordingly, the specification fails to demonstrate possession of the claimed anti- SIRPα antibodies.
Therefore, the claimed anti- SIRPα antibodies lack adequate written description because there does not appear to be any correlation between the structure of the antibodies and the functional property of binding to the extracellular domain of SIRPα and blocking the SIRPα pathway to treat cancer in a subject. Thus, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of anti- SIRPα antibodies at the time the instant application was filed.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-10, 12-22, and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over van der Berg (WO 2009/131453 A1) in view of Johnson et al, (WO 2015/048312 A1), hereinafter Johnson as evidenced by ThermoFisher Scientific ("Macrophage Cell Overview”. Thermo Fisher Scientific. Accessed: January 14, 2026).
Van der Berg discloses agents capable of inhibiting CD47-SIRPα interaction in order to reduce suppression of the cytolytic and/or phagocytic response of immune effector cells when administered for the treatment of various cancers, such as non-Hodgkin's lymphoma, breast cancer, chronic, lymphocytic leukemia, or colorectal cancer, wherein said agent is an anti-SIRPα antibody (see entire document, including Background, Examples, and Claims, in particular, preferred agents disclosed on Pages 7 – 8 and exemplary diseases on Page 10). A composition comprising the anti-SIRPα compound and a therapeutic agent (e.g. an antibody) that can trigger a host’s immune effector cells against an aberrant cell is further disclosed (Page 4, Ln. 15-25). Specifically, in the presence of 5 μg/mL of the anti-SIRPα antibody ED9 or its Fab’ fragments, rat CC531 colon carcinoma cells are readily phagocytosed by macrophage effector cells in vitro (Example 1). Given that SIRPa is a transmembrane glycoprotein (see Gene ID: 140885 for SIRPa, OA.Appendix), the anti-SIRPa antibodies disclosed by van der Berg, including clone ED9, bind to the extracellular domain of SIRPa. Thus, the anti-SIRPA antibodies of van der Berg comprise a ‘means for binding to the ECD of SIRPa’ and a ‘means for disrupting the SIRPa pathway’. The independent claim requires administration of an anti-SIRPα antibody to treat cancer in a subject; therefore, the anti-SIRPα antibody is necessarily administered at some dose. The “wherein” clauses recited in instant claims 2, 3, 5, 7, 12, 14, 15, 17, 19, and 24 do not impose any additional limitations on the dose, structure of the antibody, or administration steps and thus merely state the intended results of administration, which do not confer patentable weight. Further, per the instant claims, an anti-SIRPa antibody that binds to the ECD of SIRPa and disrupts the SIRPa pathway is minimally required to achieve the functional and therapeutic outcomes set forth in the claims. Lastly, instant claims 4, 6, 16, and 18 merely define or characterize macrophages according to the markers and cytokine profiles expressed by M1 and M2 macrophages as evidenced by Macrophage Cell Overview published by Thermo Fisher Scientific (see, in particular, Figure 3 and Tables 1-4), and thus do not carry patentable weight.
Van der berg does not teach the second therapeutic agent administered to trigger a host’s immune effector cells against an aberrant cell is an anti-PD-L1 antibody.
However, Johnson teaches methods of treating cancer using combination immunotherapy comprising an inhibitor PD-1 or PD-L1 and an inhibitor of an immune checkpoint regulator for a greater therapeutic effect (see entire document, in particular, Abstract, Summary of Invention, and Claims), wherein the inhibitor is an antibody such as a human or humanized antibody that may be further conjugated to a cytotoxic agent (e.g. a chemotherapeutic agent, biologic agent, toxin, or radioactive isotope) (Page 3, Ln. 15-18, Page 3, Ln. 4-17) and the immune checkpoint regulator includes SIRP-alpha (Page 19, Ln. 1- 9).
It would have been obvious to one of ordinary skill in the art to administer an anti-PD-L1 antibody as a second therapeutic agent in the method for treating cancers disclosed by van der Berg. One of ordinary skill in the art would have been motivated to do so since combination immunotherapy with an anti-PD-L1 antibody can achieve greater therapeutic benefit in the treatment of cancer as taught by Johnson. Therefore, one of ordinary skill in the art would expect that administering an anti-SIRPa antibody in combination with an anti-PD-L1 antibody can effectively treat cancer in a subject.
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 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.
Claims 1-10, 12-22, and 24-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11884723B2 in view of Johnson et al, (WO 2015/048312 Al), hereinafter Johnson as evidenced by ThermoFisher Scientific ("Macrophage Cell Overview”. Thermo Fisher Scientific. Accessed: January 14, 2026).
The issued claims recite a method of treating a cancer in a subject that expresses SIRPa v1, comprising administering to the subject an anti-human SIRPa antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof binds specifically to human SIRPa v1 and inhibits the binding of human CD47 to human SIRPa v1 (issued claims 1, 2, 3, 6, 8, and 9). At least one second therapeutic compound such as an immunotherapeutic agent is further administered with the anti-SIRPa antibody (issued claim 9). The cancer treated include a solid cancer such as breast, ovarian, and lung cancer (issued claims 18-20). Given that SIRPa is a transmembrane glycoprotein (see Gene ID: 140885 for SIRPa, OA.Appendix),, the anti-SIRPa antibodies of the issued claims bind to the extracellular domain of SIRPa. Thus, the anti-SIRPA antibodies of the issued claims comprise a ‘means for binding to the ECD of SIRPa’ and a ‘means for disrupting the SIRPa pathway’. The independent claim of the instant application requires administration of an anti-SIRPα antibody to treat cancer in a subject; therefore, the anti-SIRPα antibody is necessarily administered at some dose. The “wherein” clauses recited in instant claims 2, 3, 5, 7, 12, 14, 15, 17, 19, and 24 do not impose any additional limitations on the dose, structure of the antibody, or administration steps and thus merely state the intended results of administration, which do not confer patentable weight. Further, per the instant claims, an anti-SIRPa antibody that binds to the ECD of SIRPa and disrupts the SIRPa pathway is minimally required to achieve the functional and therapeutic outcomes set forth in the claims. Lastly, instant claims 4, 6, 16, and 18 merely define or characterize macrophages according to the markers and cytokine profiles expressed by M1 and M2 macrophages as evidenced by Macrophage Cell Overview published by Thermo Fisher Scientific (see, in particular, Figure 3 and Tables 1-4), and thus do not carry patentable weight.
The issued claims do not specifically teach that the second therapeutic administered in combination with the anti-SIRPα antibody is a blocking anti-PD-L1 antibody.
However, Johnson teaches methods of treating cancer using combination immunotherapy comprising an inhibitor of PD-L1 and an inhibitor of an immune checkpoint regulator for a greater therapeutic effect (see entire document, in particular, Abstract, Summary of Invention, and Claims), wherein the inhibitor is an antibody such as a humanized or human antibody that may be further conjugated to a cytotoxic agent (e.g. a chemotherapeutic agent, biologic agent, toxin, or radioactive isotope) (Page 3, Ln. 15-18, Page 3, Ln. 4-17) and the immune checkpoint regulator includes SIRP-alpha (Page 19, Ln. 1- 9).
It would have been obvious to one of ordinary skill in the art to administer an anti-PD-L1 antibody as a second therapeutic agent in the method for treating cancers disclosed by the issued claims. One of ordinary skill in the art would have been motivated to do so since combination immunotherapy with an anti-PD-L1 antibody can achieve greater therapeutic benefit in the treatment of cancer as taught by Johnson. Therefore, one of ordinary skill in the art would expect that administering an anti-SIRPa antibody of the issued claims in combination with an anti-PD-L1 antibody can effectively treat cancer in a subject.
Claims 1-7, 10, 12-19, 22, 24, and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-47 of U.S. Patent No. 11279766B2 as evidenced by ThermoFisher Scientific ("Macrophage Cell Overview”. Thermo Fisher Scientific. Accessed: January 14, 2026).
The issued claims recite a pharmaceutical composition comprising an anti-SIRPa antibody and at least one second therapeutic agent, wherein the anti-SIRPa antibody is an antagonist of SIRPa and inhibits binding of SIRPa to CD47 and the second therapeutic agent is an immune checkpoint blocker or activator, including anti-PDL1, anti-PD1, anti-CD137, and anti-CTLA4 (issued claims 1, 15, 16, 17, 18, 20, 26 and 27). Given that SIRPa is a transmembrane glycoprotein(see Gene ID: 140885 for SIRPa, OA.Appendix),, the anti-SIRPa antibodies of the issued claims bind to the extracellular domain of SIRPa. Thus, the anti-SIRPA antibodies of the issued claims comprise a ‘means for binding to the ECD of SIRPa’ and a ‘means for disrupting the SIRPa pathway’. The independent claim of the instant application requires administration of an anti-SIRPα antibody to treat cancer in a subject; therefore, the anti-SIRPα antibody is necessarily administered at some dose. The “wherein” clauses recited in instant claims 2, 3, 5, 7, 12, 14, 15, 17, 19, and 24 do not impose any additional limitations on the dose, structure of the antibody, or administration steps and thus merely state the intended results of administration, which do not confer patentable weight. Further, per the instant claims, an anti-SIRPa antibody that binds to the ECD of SIRPa and disrupts the SIRPa pathway is minimally required to achieve the functional and therapeutic outcomes set forth in the claims. Lastly, instant claims 4, 6, 16, and 18 merely define or characterize macrophages according to the markers and cytokine profiles expressed by M1 and M2 macrophages as evidenced by Macrophage Cell Overview published by Thermo Fisher Scientific (see, in particular, Figure 3 and Tables 1-4), and thus do not carry patentable weight.
Thus, the issued claims meet the limitations of instant claims 1-7, 10, 12-19, 22, 24, and 25.
Claims 1-10, 12-22, and 24-25 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 12252546B2 in view of van der Berg (WO 2009/131453 A1) and Johnson et al, (WO 2015/048312 A1), hereinafter Johnson as evidenced by ThermoFisher Scientific ("Macrophage Cell Overview”. Thermo Fisher Scientific. Accessed: January 14, 2026).
The issued claims claims recite a nucleic acid encoding an anti-SIRPa antagonist antibody that inhibits the binding of SIRPa to CD47 (issued claims 1 and 16). Given that SIRPa is a transmembrane glycoprotein (see Gene ID: 140885 for SIRPa, OA.Appendix),, the anti-SIRPa antibodies of the issued claims bind to the extracellular domain of SIRPa. Thus, the anti-SIRPA antibodies of the issued claims comprise a ‘means for binding to the ECD of SIRPa’ and a ‘means for disrupting the SIRPa pathway’.
The issued claims do not recite a method for treating cancer in a subject comprising administering the anti-SIRPa antibody in combination with an anti-PD-L1 antibody.
However, Van der Berg teaches agents capable of inhibiting CD47-SIRPα interaction in order to reduce suppression of the cytolytic and/or phagocytic response of immune effector cells when administered for the treatment of various cancers, such as non-Hodgkin's lymphoma, breast cancer, chronic, lymphocytic leukemia, or colorectal cancer, wherein said agent is an anti-SIRPα antibody (see entire document, including Background, Examples, and Claims, in particular, preferred agents disclosed on Pages 7 – 8 and exemplary diseases on Page 10). A composition comprising the anti-SIRPα compound and a therapeutic agent (e.g. an antibody) that can trigger a host’s immune effector cells against an aberrant cell is further disclosed (Page 4, Ln. 15-25). The independent claim of the instant application requires administration of an anti-SIRPα antibody to treat cancer in a subject; therefore, the anti-SIRPα antibody is necessarily administered at some dose. The “wherein” clauses recited in instant claims 2, 3, 5, 7, 12, 14, 15, 17, 19, and 24 do not impose any additional limitations on the dose, structure of the antibody, or administration steps and thus merely state the intended results of administration, which do not confer patentable weight. Further, per the instant claims, an anti-SIRPa antibody that binds to the ECD of SIRPa and disrupts the SIRPa pathway is minimally required to achieve the functional and therapeutic outcomes set forth in the claims. Lastly, instant claims 4, 6, 16, and 18 merely define or characterize macrophages according to the markers and cytokine profiles expressed by M1 and M2 macrophages as evidenced by Macrophage Cell Overview published by Thermo Fisher Scientific (see, in particular, Figure 3 and Tables 1-4), and thus do not carry patentable weight.
Johnson further teaches methods of treating cancer using combination immunotherapy comprising an inhibitor PD-1 or PD-L1 and an inhibitor of an immune checkpoint regulator for a greater therapeutic effect (see entire document, in particular, Abstract, Summary of Invention, and Claims), wherein the inhibitor is an antibody such as a human or humanized antibody that may be further conjugated to a cytotoxic agent (e.g. a chemotherapeutic agent, biologic agent, toxin, or radioactive isotope) (Page 3, Ln. 15-18, Page 3, Ln. 4-17) and the immune checkpoint regulator includes SIRP-alpha (Page 19, Ln. 1- 9).
It would have been obvious to one of ordinary skill in the art to administer the anti-SIRPa antibody of the issued claims to a subject having cancer in combination with an anti-PD-L1 antibody as a second therapeutic agent. One of ordinary skill in the art would have been motivated to do so since anti-SIRPa antibodies can be used to treat cancer in a subject as taught by Van der Berg and combination immunotherapy with anti-PD-L1 can achieve a greater therapeutic benefit in the anti-cancer treatment as taught by Johnson. Therefore, one of ordinary skill in the art would expect that the anti-SIRPa antibody of the issued claims administered in combination with an anti-PD-L1 antibody can be used to effectively treat cancer in a subject.
Thus, the co-pending claims meet the limitations of the instant claims.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIA TAYLOR whose telephone number is (571)272-6336. The examiner can normally be reached 8:30 - 5:00 M-F.
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) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MISOOK YU can be reached at 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 published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LIA E TAYLOR/Examiner, Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641