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 Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 36 and 41-43 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to non-statutory subject matter. Claims 36, 41, and 42 do not fall within at least one of the four categories of patent eligible subject matter because the claims are directed to the “use” of the conjugate. The claims are not directed toward a: 1) composition of matter; 2) machine; 3) manufacture; or 4) process, but rather a “use” of a composition of the conjugate, wherein no active method steps are present to suggest a process is being claimed. "Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101 MPEP 2173.05(q).
Additionally, claim 43 does not fall within at least one of the four categories of patent eligible subject matter because the claim lacks a preamble directing the claim toward a: 1) composition of matter; 2) machine; 3) manufacture; or 4) process.
Claim Rejections - 35 USC § 112(b)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 8-10,13, 14, 17-22, 29, 30, 33, 36, and 41-43 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “a treatment-effective combination” comprising SIRPaFc and an anti-VEGF agent. It is unclear if “combination” here indicates that these two components are 1. Part of regimen where they are given together in the course of treatment (not necessarily at the same time or at a particular interval), 2. An admixture, 3. A fusion molecule, or 4. Given at a particular interval (e.g. concurrently). Similarly, claims 35 and 36 recite a combination of anti-cancer agents and the use of the combination.
For the purpose of compact prosecution, combination in claims 1, 35, and 36 is interpreted as a regimen where the two components are given together in the course of treatment, but not necessarily at the same time or at a particular interval.
Claims 8-10,13, 14, 17-22, 29, 30, 33, 36, 41, and 42 are rejected for depending from claims 1, 35, or 36 and failing to remedy the indefiniteness.
Claim 10 recites “the anti-VEGF agent is bevacizumab or a VEGF-binding fragment or variant of bevacizumab.” It is unclear if “a VEGF-binding fragment” is of bevacizumab or not. For the purpose of compact prosecution, the claim is interpreted as reciting “the anti-VEGF agent is bevacizumab, a VEGF-binding fragment of bevacizumab, or variant of bevacizumab.”
Claims 36, 41, and 42 are indefinite because they attempt to claim a process without setting forth any steps involved in the process. MPEP 2173.05(q) states attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness. Recitation of a use without any active, positive steps delimiting how this use is actually practiced is indefinite. For the purpose of compact prosecution, claims 36, 41, and 42 are interpreted as requiring administering the combination of anti-cancer agents: SIRPa and bevacizumab. Note that claim 35 recites instructions “together with” the combination of anti-cancer agents. Claim 36 is not interpreted as requiring the use of the instructions which are a separate component from the combination.
Claim 43 is indefinite because it does not set forth a statutory category. Because claim 44 depends from claim 43 and recites “[t]he kit”, claim 43 is interpreted, for the purpose of compact prosecution, as reciting “A kit comprising […]”.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 21, 36, 41, and 42 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 36, 41, and 42 depend from claim 35 and recite the use of the combination according to claim 35. Claims 36, 41, and 42 are indefinite and interpreted as reciting a method requiring administering the combination of anti-cancer agents of claim 35. Claim 35 recites the combination of anti-cancer agents together with instructions teaching the use. Claims 36, 41, and 42 do not require the use of the instructions – only administering the combination of anti-cancer agents. The combination of anti-cancer agents is a distinct group of components from the instructions. Thus, claims 36, 41, and 42 fail to include all limitations of claim 35.
Claim 21 depends from claim 20. Claim 20 recites the CD47+ disease cells comprise CD47+ cancer cells. Claim 21 recites the cancer cells are blood cancer cells or solid tumor cells. These two options encompass all options for cancer cells; thus, claim 21 fails to further limit claim 20.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claims 1, 8, 13, 14, 20, 21, and 29 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Wan et al. (US 2021/0154269 A1; Published: May 27, 2021).
Regarding claims 1, 8, 13, 14, and 20, Wan et al. teaches methods of treating cancer comprising an effective amount of: (a) a polypeptide comprising a SIRPa D1 domain variant and an Fc domain variant, (b) an anti-HER2 antibody, (c) an anti-VEGFR2 antibody, and (d) paclitaxel; see paragraph 0013 and claim 29. Regarding claims 20, 21, and 29, Wan et al. teaches treating the solid tumors: gastric cancer or gastroesophageal junction (GEJ) cancer with this combination; see paragraph 0019.
Thus, Wan et al. anticipates claims 1, 8, 13, 14, 20, 21, and 29.
Claims 1, 20, 21, 29, and 30 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Zhang et al. (Journal for ImmunoTherapy of Cancer. 7: 346; Published: December 11, 2019).
Regarding claims 1, 20, 21, 29, and 30, Zhang et al. teaches methods of treating lung cancer comprising administering a CD47 binding SIRPaFc and an anti-VEGF agent, VEGFR1-Fc; see Figure 4 for example.
Thus, Zhang et al. anticipates claims 1, 20, 21, 29, and 30.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 43 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Wan et al. (US 2021/0154269 A1; Published: May 27, 2021).
The teachings of Wan et al. as related to claim(s) 1, 8, 13, 14, 20, 21, 29, and 36, from which these claims depend are given previously in this Office action and are fully incorporated here.
Wan et al. does not teach a kit comprising the SIRPaFc and anti-VEGF agent.
Regarding claims 43 and 44, Wan et al. teaches a kit comprising a polypeptide comprising a SIRPa D1 domain variant and an Fc domain variant in a pharmaceutically acceptable carrier, for use in combination with an anti-HER2 antibody, an anti-VEGFR2 antibody, and paclitaxel; see paragraph 0019.
Given that Wan et al. teaches a method of treating cancer comprising administering a regimen which comprises the SIRPaFc and an anti-VEGF agent (i.e. the anti-VEGFR2 antibody) and teaches a kit comprising the SIRPaFc polypeptide in a carrier for use in the combination regimen, it would have been obvious to one of ordinary skill in the art to modified the kit to further comprise the other components of the regimen in unit dose formulations, including the anti-VEGF agent, not as an admixture, since these components will all be administered together in the same regimen. One would have been motivated to make this modification for the convenience of having all components of the regimen together. Similarly, one would have been motivated to provide these components in dose unit formulations for convenience and ease of use.
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 application, as evidenced by the references.
Claims 1, 8-10, 17-21, 29, 33, 35, 36, 41, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Journal for ImmunoTherapy of Cancer. 7: 346; Published: December 11, 2019) in view of Uger et al. (US 2018/0312563 A1; Published: November 1, 2018) and Prescribing Information for Avastin (Published: December 2020).
The teachings of Zhang et al. as related to claim(s) 1, 20, 21, 29, and 30, from which these claims depend are given previously in this Office action and are fully incorporated here.
Zhang et al. does not teach the sequence of the SIRPaFc nor treating solid tumors besides lung cancer with the combination.
Regarding claims 17-19, Uger et al. teaches a SIRPaFc protein comprising SEQ ID NOs: 25 and 26 which are 100% identical to instant SEQ ID NOs: 3 and 8, respectively. Further, SEQ ID NOs: 25 and 26 of Uger et al. comprise SEQ ID NO: 1, which is the IgV of human SIRPa variant 2; see paragraphs 0021-0022. See the alignment below of SEQ ID NO: 1, in the Qy line, with SEQ ID NOs: 25 or 26, in the Db line.
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Regarding claims 21, 29, and 33, Uger et al. teaches administering the SIRPaFc protein to treat solid tumors of the bladder, brain (e.g. glioblastoma), breast, lung, colon (e.g. colorectal), ovaries, prostate, or liver (e.g. hepatocellular carcinoma); see paragraph 0058 for example.
Neither Zhang et al. nor Uger et al. teach administering the SIRPaFc in combination with an anti-VEFG antibody such as bevacizumab.
Regarding claims 8-10, 35, 41, and 42, the Prescribing Information for Avastin (bevacizumab; anti-VEGF antibody) teaches using for the treatment of cancers, including lung cancer, for example; see Indications and Usage.
Regarding claim 35, the Prescribing Information for Avastin provides instructions for use; see Dosage and Administration, for example.
Given the Zhang et al. teaches that the SIRPa used in the fusion proteins comprises the first extracellular domain of SIRPa (see Reagents for example) and Uger et al. teaches that the preferred SIRPa is a single domain (SEQ ID NO: 22), it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to substitute the SIRPaFc taught by Uger et al. in the method of treating cancer with the combination of SIRPaFc and an anti-VEGF agent taught by Zhang et al.
Moreover, Zhang et al. teaches that bevacizumab (anti-VEGF antibody) monotherapy inhibited tumor growth similar to the VEGFR1-Fc of the combination regimen (see Zhang et al. Supplemental Figure 1) and because both agents block the binding of VEGF to VEGFR, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to substitute bevacizumab (anti-VEGF antibody) for the VEGFR1-Fc in the combination regimen taught by Zhang et al.
Further, because Uger et al. teaches that the SIRPaFc is appropriate for treating blood and solid cancers, including brain, liver, and lung, for example, and the Prescribing Information for Avastin teaches treating similar cancers, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat other solid tumors beyond lung cancer as taught by Zhang et al. with the combination of SIRPaFc and an anti-VEGF agent.
Finally, the Prescribing Information of Avastin provides instructions for use. It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to make a combination regimen comprising SIRPaFc and an anti-VEGF agent as taught by Zhang et al. and include instructions for use as exemplified by the Prescribing Information of Avastin.
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 application, as evidenced by the references.
Claims 1, 8, 13, 14, 17-19, 21, 29, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Journal for ImmunoTherapy of Cancer. 7: 346; Published: December 11, 2019) in view of Uger et al. (US 2018/0312563 A1; Published: November 1, 2018), Prescribing Information for Cyramza (Published: June 2020), and Lai et al. (Frontiers in Oncology. 11:637823; Published: May 10, 2021).
The teachings of Zhang et al. as related to claim(s) 1, 20, 21, 29, and 30, from which these claims depend are given previously in this Office action and are fully incorporated here.
Zhang et al. does not teach the sequence of the SIRPaFc nor treating solid tumors besides lung cancer with the combination.
Regarding claims 17-19, Uger et al. teaches a SIRPaFc protein comprising SEQ ID NOs: 25 and 26 which are 100% identical to instant SEQ ID NOs: 3 and 8, respectively. Further, SEQ ID NOs: 25 and 26 of Uger et al. comprise SEQ ID NO: 1, which is the IgV of human SIRPa variant 2; see paragraphs 0021-0022. See the alignment below of SEQ ID NO: 1, in the Qy line, with SEQ ID NOs: 25 or 26, in the Db line.
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Regarding claims 21, 29, and 33, Uger et al. teaches administering the SIRPaFc protein to treat solid tumors of the bladder, brain (e.g. glioblastoma), breast, lung, colon (e.g. colorectal), ovaries, prostate, or liver (e.g. hepatocellular carcinoma); see paragraph 0058 for example.
Neither Zhang et al. nor Uger et al. teach administering the SIRPaFc in combination with an anti-VEFGR2 antibody.
Regarding claims 8, 13, and 14, the Prescribing information for Cyramza (ramucirumab; anti-VEGFR2 antibody) teaches using for the treatment of cancers, including lung cancer, for example; see Indications and Usage.
Given the Zhang et al. teaches that the SIRPa used in the fusion proteins comprises the first extracellular domain of SIRPa (see Reagents for example) and Uger et al. teaches that the preferred SIRPa is a single domain (SEQ ID NO: 22), it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to substitute the SIRPaFc taught by Uger et al. in the method of treating cancer with the combination of SIRPaFc and an anti-VEGF agent taught by Zhang et al.
Moreover, Zhang et al. teaches that bevacizumab (anti-VEGF antibody) monotherapy inhibited tumor growth similar to the VEGFR1-Fc of the combination regimen; see Zhang et al. Supplemental Figure 1. Additionally, Lai et al. teaches that the overall survival outcomes for CRC patients treated with anti-VEGF antibody, an anti-VEGFR2 antibody, or a VEGFR-Fc were similar; see Table 2. Because all three agents block the binding of VEGF to VEGFR, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to substitute the VEGFR1-Fc in the combination regimen taught by Zhang et al. with an anti-VEGFR2 antibody such as Cyramza.
Further, because Uger et al. teaches that the SIRPaFc is appropriate for treating blood and solid cancers, including brain, liver, and lung, for example, and the Prescribing Information for Avastin teaches treating similar cancers, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat other solid tumors beyond lung cancer as taught by Zhang et al. with the combination of SIRPaFc and an anti-VEGF agent.
Finally, the Prescribing Information of Cyramza provides instructions for use. It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to make a combination regimen comprising SIRPaFc and an anti-VEGF agent as taught by Zhang et al. and include instructions for use as exemplified by the Prescribing Information of Cyramza.
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 application, as evidenced by the references.
Claims 1 and 17-22 are rejected under 35 U.S.C. 103 as being unpatentable over Uger et al. (US 2018/0312563 A1; Published: November 1, 2018), Fiedler et al. (Blood. 120 (21): 613; Published: November 16, 2021), and Ikezoe et al. (Molecular Cancer Therapeutics. 5(10): 2522-2530; Published: December 2020).
Regarding claims 17-19, Uger et al. teaches a SIRPaFc protein comprising SEQ ID NOs: 25 and 26 which are 100% identical to instant SEQ ID NOs: 3 and 8, respectively. Further, SEQ ID NOs: 25 and 26 of Uger et al. comprise SEQ ID NO: 1, which is the IgV of human SIRPa variant 2; see paragraphs 0021-0022. See the alignment below of SEQ ID NO: 1, in the Qy line, with SEQ ID NOs: 25 or 26, in the Db line.
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Regarding claims 21 and 22, Uger et al. teaches administering the SIRPaFc protein to treat hematological cancer; see paragraph 0054 for example.
Uger et al. does not teach an anti-VEGF agent for the treatment of blood cancer.
Fiedler et al. teaches treating patients with the blood cancer, AML, by administering a regimen comprising sunitinib; see Conclusion. It is noted that the instant Specification does not include a limiting definition of anti-VEGF agents. Regarding anti-VEGF agents the Specification states that "’Anti-VEGF’ agents include agents that bind circulating VEGF-A and thereby inhibit interaction with VEGF receptors (VEGFR-1, VEGFR-2, etc.) the signalling of which is involved in tumour angiogenesis.”; see page 14. While anti-VEGF agents may include agents which bind to VEGF, the genus is not limited to only those agents which bind VEGF nor to antibodies only. This interpretation is affirmed by claim 14 which recites the agent is an anti-VEGFR2 antibody. Ikezoe et al. evidences that sunitinib, a TKI, inhibits VEGFR; see page 2522.
Given that Uger et al. teaches that SIRPaFc is an appropriate treatment for hematological cancers and Fiedler et al. as evidenced by Ikezoe et al. teaches treating the hematological cancer, AML, with the anti-VEGF agent, sunitinib, it would have been obvious to one of ordinary skill in the art to combine SIRPaFc with sunitinib for the treatment of the hematological cancer, AML. One would have had a reasonable expectation of success and predictability treating AML with the combination because each element merely performs the same function as when administered independently and Uger et al. and Fiedler et al. teach the use of each medication for the treatment of the hematological cancer, AML. Further, Uger et al. teaches that SIRPaFc may be administered “in combination with any other agent useful in the treatment of the targeted indication”; see paragraph 0059.
Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalents for the same purpose. The court has held that it is obvious to combine two elements each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
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 application, as evidenced by the references.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 8, 13, 14, 17, 18, 20, 21, 29, 43, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,969,789 B2 in view of Wan et al. (US 2021/0154269 A1; Published: May 27, 2021).
Claims 1, 8, 13, 14, 17, 19, 20, 21, 29, 43, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,906,954 B2 in view of Wan et al. (US 2021/0154269 A1; Published: May 27, 2021).
The following analysis applies to both rejections over the claims of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2.
Issued claims 1-4 of U.S. Patent No. 9,969,789 B2 recite a SIRPa fusion protein (i.e. a SIRPaFc) comprising SEQ ID NO: 25 for inhibiting the growth or proliferation of CD47+ disease cells. Regarding instant claims 17 and 18, instant SEQ ID NO: 3 is 100% identical to SEQ ID NO: 25. The issued Specification states that CD47+ disease cells include CD47+ cancer cells; see column 2 lines 52-53 for example.
Issued claims 1-14 of U.S. Patent No. 10,906,954 B2 recite a SIRPa fusion protein (i.e. SIRPaFc) comprising SEQ ID NO: 26. Regarding instant claims 17 and 19, instant SEQ ID NO: 8 is 100% identical to SEQ ID NO: 26. The issued Specification states that CD47+ disease cells include CD47+ cancer cells; see column 2 lines 54-55 for example.
The issued claims do not teach treating with the combination of SIRPaFc and anti-VEGFR2 antibody.
Regarding claims 1, 8, 13, 14, and 20, Wan et al. teaches methods of treating cancer comprising an effective amount of: (a) a polypeptide comprising a SIRPa D1 domain variant and an Fc domain variant, (b) an anti-HER2 antibody, (c) an anti-VEGFR2 antibody, and (d) paclitaxel; see paragraph 0013 and claim 29. Regarding claims 20, 21, and 29, Wan et al. teaches treating the solid tumors: gastric cancer or gastroesophageal junction (GEJ) cancer with this combination; see paragraph 0019.
Regarding claims 43 and 44, Wan et al. teaches a kit comprising a polypeptide comprising a SIRPa D1 domain variant and an Fc domain variant in a pharmaceutically acceptable carrier, for use in combination with an anti-HER2 antibody, an anti-VEGFR2 antibody, and paclitaxel; see paragraph 0019.
Given that the issued claims teach a similar SIRPaFc for the treatment of CD47+ disease cells, which include cancer, and Wan et al. teaches treating cancer with a combination of SIRPaFc and anti-VEGFR2 antibody, it would have been obvious and one would have had a reasonable expectation of success to substitute the SIRPaFc of the issued claims in the method taught by Wan et al. for the treatment of solid tumors.
Additionally, given that Wan et al. teaches a method of treating cancer comprising administering a regimen which comprises the SIRPaFc and an anti-VEGF agent (i.e. the anti-VEGFR2 antibody) and teaches a kit comprising the SIRPaFc polypeptide in a carrier for use in the combination regimen, it would have been obvious to one of ordinary skill in the art to modified the kit to comprise the SIRPaFc taught by the issued claims and further comprise the other components of the regimen in unit dose formulations, including the anti-VEGF agent, not as an admixture, since these components will all be administered together in the same regimen. One would have been motivated to make this modification for the convenience of having all components of the regimen together. Similarly, one would have been motivated to provide these components in dose unit formulations for convenience and ease of use.
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 application, as evidenced by the references.
Claims 1, 17, 18, 20, 21, 29, 30, 43, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,969,789 B2 in view of Zhang et al. (Journal for ImmunoTherapy of Cancer. 7: 346; Published: December 11, 2019).
Claims 1, 17, 19, 20, 21, 29, 30, 43, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,906,954 B2 in view of Zhang et al. (Journal for ImmunoTherapy of Cancer. 7: 346; Published: December 11, 2019).
The following analysis applies to both rejections over the claims of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2.
Issued claims 1-4 of U.S. Patent No. 9,969,789 B2 recite a SIRPa fusion protein (i.e. a SIRPaFc) comprising SEQ ID NO: 25 for inhibiting the growth or proliferation of CD47+ disease cells.
Regarding instant claims 17 and 18, instant SEQ ID NO: 3 is 100% identical to SEQ ID NO: 25. The issued Specification states that CD47+ disease cells include CD47+ cancer cells; see column 2 lines 52-53 for example.
Issued claims 1-14 of U.S. Patent No. 10,906,954 B2 recite a SIRPa fusion protein (i.e. SIRPaFc) comprising SEQ ID NO: 26. Regarding instant claims 17 and 19, instant SEQ ID NO: 8 is 100% identical to SEQ ID NO: 26. The issued Specification states that CD47+ disease cells include CD47+ cancer cells; see column 2 lines 54-55 for example.
The issued claims do not teach treating with the combination of SIRPaFc and anti-VEGF agent.
Regarding claims 1, 20, 21, 29, and 30, Zhang et al. teaches methods of treating lung cancer comprising administering a CD47 binding SIRPaFc and an anti-VEGF agent, VEGFR1-Fc; see Figure 4 for example.
Given that the issued claims teach a similar SIRPaFc for the treatment of CD47+ disease cells, which include cancer, and Zhang et al. teaches treating cancer with a combination of SIRPaFc and anti-VEGF agent, it would have been obvious and one would have had a reasonable expectation of success to substitute the SIRPaFc of the issued claims in the method taught by Zhang et al. for the treatment of solid tumors.
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 application, as evidenced by the references.
Claims 8-10, 33, 35, 36, 41, and 42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,969,789 B2 in view of Zhang et al. (Journal for ImmunoTherapy of Cancer. 7: 346; Published: December 11, 2019), as applied to claims 1, 17, 18, 20, 21, 29, 30, 43, and 44, and further in view of Prescribing Information for Avastin (Published: December 2020).
Claims 8-10, 33, 35, 36, 41, and 42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,906,954 B2 in view of Zhang et al. (Journal for ImmunoTherapy of Cancer. 7: 346; Published: December 11, 2019), as applied to claims 1, 17, 19, 20, 21, 29, 30, 43, and 44, and further in view of Prescribing Information for Avastin (Published: December 2020).
The following analysis applies to both rejections over the claims of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2.
The teachings of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2 in view of Zhang et al. as related to claim(s) 1, 17, 18, 20, 21, 29, 30, 43, and 44 or 1, 17, 19, 20, 21, 29, 30, 43, and 44, from which these claims depend are given previously in this Office action and are fully incorporated here.
Regarding instant claim 33, the issued Specifications of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2 state that CD47+ disease cells include cancer cells and solid tumors of the bladder, brain, breast, lung, colon, ovaries, prostate, and liver; see column 12 lines 31-33.
Neither the issued claims nor Zhang et al. teach administering the SIRPaFc in combination with an anti-VEFG antibody such as bevacizumab.
Regarding claims 8-10, 35, 36, 41, and 42, the Prescribing Information for Avastin (bevacizumab; anti-VEGF antibody) teaches using for the treatment of cancers, including lung cancer, for example; see Indications and Usage.
Regarding claim 35, the Prescribing Information for Avastin provides instructions for use; see Dosage and Administration, for example.
Since Zhang et al. teaches that bevacizumab (anti-VEGF antibody) monotherapy inhibited tumor growth similar to the VEGFR1-Fc of the combination regimen (see Zhang et al. Supplemental Figure 1) and because both agents block the binding of VEGF to VEGFR, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to substitute bevacizumab (anti-VEGF antibody) for the VEGFR1-Fc in the combination regimen taught by the issued claims and Zhang et al.
Further, because the instant Specification states that the SIRPaFc is appropriate for treating blood and solid cancers, including brain, liver, and lung, for example, and the Prescribing Information for Avastin teaches treating similar cancers, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat other solid tumors beyond lung cancer as taught by Zhang et al. with the combination of the SIRPaFc of the issued claims and an anti-VEGF agent.
Finally, the Prescribing Information of Avastin provides instructions for use. It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to make a combination regimen comprising the SIRPaFc of the issued claims and an anti-VEGF agent as taught by Zhang et al. and include instructions for use as exemplified by the Prescribing Information of Avastin.
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 application, as evidenced by the references.
Claims 8, 13, 14, and 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,969,789 B2 in view of Zhang et al. (Journal for ImmunoTherapy of Cancer. 7: 346; Published: December 11, 2019), as applied to claims 1, 17, 18, 20, 21, 29, 30, 36, 41, 43, and 44, and further in view of Prescribing Information for Cyramza (Published: June 2020), and Lai et al. (Frontiers in Oncology. 11:637823; Published: May 10, 2021).
Claims 8, 13, 14, and 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,906,954 B2 in view of Zhang et al. (Journal for ImmunoTherapy of Cancer. 7: 346; Published: December 11, 2019), as applied to claims 1, 17, 19, 20, 21, 29, 30, 36, and 42-44, and further in view of Prescribing Information for Cyramza (Published: June 2020), and Lai et al. (Frontiers in Oncology. 11:637823; Published: May 10, 2021).
The following analysis applies to both rejections over the claims of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2.
The teachings of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2 in view of Zhang et al. as related to claim(s) 1, 17, 18, 20, 21, 29, 30, 36, 41, 43, and 44 or 1, 17, 19, 20, 21, 29, 30, 36, and 42-44, from which these claims depend are given previously in this Office action and are fully incorporated here.
Regarding instant claim 33, the issued Specifications of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2 state that CD47+ disease cells include cancer cells and solid tumors of the bladder, brain, breast, lung, colon, ovaries, prostate, and liver; see column 12 lines 31-33.
Neither the issued claims nor Zhang et al. teach administering the SIRPaFc in combination with an anti-VEFGR2 antibody.
Regarding claims 8, 13, and 14, the Prescribing information for Cyramza (ramucirumab; anti-VEGFR2 antibody) teaches using for the treatment of cancers, including lung cancer, for example; see Indications and Usage. The Prescribing Information for Cyramza provides instructions for use; see Dosage and Administration, for example.
Zhang et al. teaches that bevacizumab (anti-VEGF antibody) monotherapy inhibited tumor growth similar to the VEGFR1-Fc of the combination regimen; see Zhang et al. Supplemental Figure 1. Additionally, Lai et al. teaches that the overall survival outcomes for CRC patients treated with anti-VEGF antibody, an anti-VEGFR2 antibody, or a VEGFR-Fc were similar; see Table 2. Because all three agents block the binding of VEGF to VEGFR, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to substitute the VEGFR1-Fc in the combination regimen taught by the issued claims and Zhang et al. with an anti-VEGFR2 antibody such as Cyramza.
Further, because the issued Specification states that the SIRPaFc is appropriate for treating blood and solid cancers, including brain, liver, and lung, for example, and the Prescribing Information for Avastin teaches treating similar cancers, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat other solid tumors beyond lung cancer as taught by Zhang et al. with the combination of the SIRPaFc of the issued claims and an anti-VEGF agent.
Finally, the Prescribing Information of Cyramza provides instructions for use. It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to make a combination regimen comprising the SIRPaFc of the issued claims and an anti-VEGF agent as taught by Zhang et al. and include instructions for use as exemplified by the Prescribing Information of Cyramza.
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 application, as evidenced by the references.
Claims 1, 17, 18, 20, 21, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,969,789 B2 in view of Uger et al. (US 2018/0312563 A1; Published: November 1, 2018), Fiedler et al. (Blood. 120 (21): 613; Published: November 16, 2021), and Ikezoe et al. (Molecular Cancer Therapeutics. 5(10): 2522-2530; Published: December 2020).
Claims 1, 17, 19, 20, 21, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,906,954 B2 in view of Uger et al. (US 2018/0312563 A1; Published: November 1, 2018), Fiedler et al. (Blood. 120 (21): 613; Published: November 16, 2021), and Ikezoe et al. (Molecular Cancer Therapeutics. 5(10): 2522-2530; Published: December 2020).
The following analysis applies to both rejections over the claims of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2.
Issued claims 1-4 of U.S. Patent No. 9,969,789 B2 recite a SIRPa fusion protein (i.e. a SIRPaFc) comprising SEQ ID NO: 25 for inhibiting the growth or proliferation of CD47+ disease cells. Regarding instant claims 17 and 18, instant SEQ ID NO: 3 is 100% identical to SEQ ID NO: 25. The issued Specification states that CD47+ disease cells include CD47+ cancer cells; see column 2 lines 52-53 for example. Regarding claims 21 and 22, the issued Specification states that CD47+ cancer includes hematological or blood cancers; see column 11 line 62 – column 12 line 28.
Issued claims 1-14 of U.S. Patent No. 10,906,954 B2 recite a SIRPa fusion protein (i.e. SIRPaFc) comprising SEQ ID NO: 26. Regarding instant claims 17 and 19, instant SEQ ID NO: 8 is 100% identical to SEQ ID NO: 26. The issued Specification states that CD47+ disease cells include CD47+ cancer cells; see column 2 lines 54-55 for example. Regarding claims 21 and 22, the issued Specification states that CD47+ cancer includes hematological or blood cancers; see column 11 line 62 – column 12 line 28.
The issued claims do not teach treating with the combination of SIRPaFc and anti-VEGF agent.
Fiedler et al. teaches treating patients with the blood cancer, AML, by administering a regimen comprising sunitinib; see Conclusion. It is noted that the instant Specification does not include a limiting definition of anti-VEGF agents. Regarding anti-VEGF agents the Specification states that "’Anti-VEGF’ agents include agents that bind circulating VEGF-A and thereby inhibit interaction with VEGF receptors (VEGFR-1, VEGFR-2, etc.) the signalling of which is involved in tumour angiogenesis.”; see page 14. While anti-VEGF agents may include agents which bind to VEGF, the genus is not limited to only those agents which bind VEGF nor to antibodies only. This interpretation is affirmed by claim 14 which recites the agent is an anti-VEGFR2 antibody. Ikezoe et al. evidences that sunitinib, a TKI, inhibits VEGFR; see page 2522.
Given that the issued Specifications of U.S. Patent No. 9,969,789 B2 and U.S. Patent No. 10,906,954 B2 states that SIRPaFc of the issued claims is an appropriate treatment for hematological cancers and Fiedler et al. as evidenced by Ikezoe et al. teaches treating the hematological cancer, AML, with the anti-VEGF agent, sunitinib, it would have been obvious to one of ordinary skill in the art to combine SIRPaFc with sunitinib for the treatment of the hematological cancer, AML. One would have had a reasonable expectation of success and predictability treating AML with the combination because each element merely performs the same function as when administered independently and issued Specifications and Fiedler et al. teach the use of each medication for the treatment of the hematological cancer, AML.
Additionally, section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalents for the same purpose. The court has held that it is obvious to combine two elements each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
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 application, as evidenced by the references.
Conclusion
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/KATHERINE ANN HOLTZMAN/Examiner, Art Unit 1646
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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