DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt is acknowledged of Applicants’ amendment and remarks, filed on 11/19/2025, in which claims 1-30 are canceled and claims 31-60 are newly added.
Claims 31-60 are pending and are examined on the merits herein.
Priority
The instant application claims foreign priority to IN202441035249, filed on 05/03/2024.
Rejections Withdrawn
Applicant’s amendment and remarks, filed 11/19/2025, with respect that the drawings are objected to because Figure 4 contains color has been fully considered and is persuasive, as replacement drawings in black and white have been filed. This objection has been withdrawn.
Applicant’s amendment and remarks, filed 11/19/2025, with respect that claims 12 and 20 are objected to has been fully considered and is persuasive, as claims 12 and 20 have been canceled. This objection has been withdrawn.
Applicant’s amendment and remarks, filed 11/19/2025, with respect that claims 2, 12, 20, 23-24, and 26-27 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention has been fully considered and is persuasive, as the claims have been canceled. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 11/19/2025, with respect that claim 22 is rejected under 35 U.S.C. 112(d), 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 has been fully considered and is persuasive, as the claim has been canceled. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 11/19/2025, with respect that claims 1-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ramachandra has been fully considered and is persuasive, as claims 1-30 are canceled. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 11/19/2025, with respect that claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patents No. 12,268,670 and 11,311,517 has been fully considered and is persuasive, as claims 1-30 are canceled. This rejection has been withdrawn.
The following are new grounds of rejection necessitated by Applicant’s amendment, in which new claim 31 recites a method of treating cancer.
Claim Rejections - 35 USC § 112(a)
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.
Claims 31-60 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 31 recites “wherein the method comprises the administration of a CD4 7-SIRPa blocking agent selected from the group consisting of the compound of formula (I), stereoisomers thereof, and a molar equivalent amount of pharmaceutically acceptable salts, solvates, amides and esters of the compound of formula (I), and stereoisomers thereof; as well as the administration of Azacitidine...” Thus the scope of claims 31-60 requires administration of three components (1) formula (I) or isomers thereof, (2) a molar equivalent of salts of formula (I), and (3) Azacitidine. The method requiring administration of these three components has not been previously disclosed and thus there is no support for the new claims. MPEP 2163(I)(B) states that newly added claims or claim limitations must be supported in the specification through express, implicit, or inherent disclosure. For purposes of compact prosecution, the claim will be interpreted as a method requiring administration of two components which are (1) formula (I), isomers thereof, or a molar equivalent amount of salts thereof and (2) Azacitidine. It is further noted that the limitation of a molar equivalent amount of pharmaceutically acceptable salts requires that the compound of formula (I) is completely in salt form, as opposed to a mixture of salt and free acid form.
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.
Claims 31-60 are rejected under 35 U.S.C. 103 as being unpatentable over Sallman et al. (Journal of Clinical Oncology, 2023; PTO-298) in view of Ramachandra et al. (WO 2020/095256 A1; IDS 05/14/2025).
Sallman discloses a clinical trial of patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with a combination of magrolimab and azacitidine (abstract). Azacitidine upregulates a cell surface prophagocytic marker, calreticulin, on malignant myeloid cells. Magrolimab is an anti-CD47 antibody that blocks CD47 binding and enhances the phagocytosis of tumor cells. Sallman teaches that anti-CD47 therapies synergize with therapeutics that increase prophagocytic signals on tumor cells (page 2816, paragraph 2).
The patients in the study are previously untreated AML patients who are unfit for standard combination chemotherapy and previously untreated intermediate/high/very high-risk MDS patients (protocol, page 70). The study includes patients with IPSS-R scores in the high and very high risk categories (table 1 on page 2817). Patients had an Eastern Cooperative Oncology Group performance status of 0-2 (page 2816, paragraph 3). Sallman teaches that all patients must have documented hemoglobin ≥ 9 g/dL within 24 hours prior to each of the first 2 doses of magrolimab infusion during initial treatment. Patients who do not meet these criteria must be transfused and have their hemoglobin rechecked to meet 9 g/dL prior to each of the first 2 doses of magrolimab (protocol, page 111, paragraph 2). Sallman discloses patient outcomes including complete and partial remission (Table 3 on page 2822).
Sallman teaches that magrolimab may be withheld if treatment-emergent and/or magrolimab-related AEs occur, which include all AEs that constitute a DLT. Magrolimab may be reintroduced at a 50% dose reduction if the severity has recovered to Grade 2 or less within 4 weeks and in the absence of disease progression (protocol, page 101, paragraph 1). A DLT is defined as any Grade 4 or higher hematologic toxicity or Grade 3 or higher non-hematologic toxicity that has worsened in severity from pretreatment baseline during the 4-week DLT Assessment Period (protocol, page 79, paragraph 1).
Azacitidine was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle (abstract). Median exposure was six cycles, with patients in the range of 1-27 cycles (page 2818). In discussing dose modifications for treatment of Azacitidine, Sallman teaches that, for patients without reduced baseline blood counts, if hematological toxicity is observed following azacitidine treatment, the next cycle of therapy should be delayed until the platelet count and the ANC have recovered (protocol, page 105). Azacitidine dose modifications due to non-hematological toxicity include delaying the next cycle until creatinine values return to normal or baseline and reducing the azacitidine dose by 50% on the next treatment cycle (protocol, page 104).
The teachings of Sallman differ from that of the instantly claimed invention in that Sallman does not teach the administration of the compound of formula (I).
Ramachandra discloses compositions comprising a CD47-SIRPα blocking agent and one or more anti-cancer agents (abstract). Ramachandra discloses a method for treating a subject presenting a dysregulated CD47 pathway, comprising administering to the subject in need thereof a therapeutically effective amount of a disclosed compound in combination with one or more anti-cancer agents (page 5, lines 4-8). Ramachandra teaches that CD47 is constitutively upregulated in a number of cancers including, among others, AML (page 2, lines 1-2). Ramachandra discloses a composition comprising the following compound as the a CD47-SIRPα blocking agent (compound 3 of claim 41).
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Ramachandra further discloses the composition comprising compound 3 in which the anti-cancer agent is a chemotherapeutic agent selected from, among others, azacitidine (claim 10). Ramachandra teaches that the disclosed compound may be administered substantially simultaneously with respect to other agents (page 29, lines 1-5). Ramachandra teaches that the disclosed compound may be administered orally (page 30, lines 3-4). Ramachandra teaches that the compound may be administered at a dosage of, among others, 10 mg/kg body weight, and that an exemplary treatment regime entails administration daily, among others (page 29, lines 6-14).
Ramachandra teaches that the compositions may comprise pharmaceutically acceptable salts of the described compounds including Na, Ca, K, Mg, Zn or other metal salts (page 39, lines 25-27).
It would have been prima facie obvious to combine the teachings of Sallman and Ramachandra before the effective filing date of the claimed invention by substituting the magrolimab of Sallman with compound 3 of Ramachandra in the method of treating MDS taught by Sallman to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to substitute the magrolimab in the method of Sallman because it is obvious to substitute the known anti-CD47 magrolimab of Sallman with the known CD47-SIRPα blocking agent of Ramachandran to obtain the predictable result of a method of treating MDS. One of ordinary skill in the art would have a reasonable expectation of success in doing so because Sallman teaches that anti-CD47 therapies synergize with therapeutics that increase prophagocytic signals on tumor cells and that azacitidine upregulates a cell surface prophagocytic marker, while Ramachandra teaches that compound 3, which is the same structure as Formula (I) of the instantly claimed invention, is a CD47-SIRPα blocking agent that may be combined with anti-cancer agents selected from, among others, azacitidine.
Regarding instant claims 35-37, the claims depend from claim 34. Neither claims 35-37, nor claim 34 upon which they depend require that the patient be a subject suffering from a relapsed and/or refractory AML. Therefore, the teaching of an alternative, wherein the subject is a newly diagnosed, meets the limitations of both claims 34 and 35-37.
Regarding instant claims 48 and 50, Ramachandra teaches that the compound may be administered at a dosage of 10 mg/kg body weight and that an exemplary treatment regime entails administration daily (page 29, lines 6-14). Thus for an average person of 80 kg, Ramachandra suggests a dose of 800 mg daily.
Response to Arguments
Applicant's arguments filed 11/19/2025 have been fully considered but they are not persuasive.
Insofar as Applicant’s arguments are applicable to the current rejections, Applicant argues that Ramachandra does not teach or suggest the treatment of hematological cancers or administration of a combination of the claimed CD47-SIRPα blocking agent and azacitidine (remarks, paragraph bridging pages 10-11).
As discussed in the above grounds of rejection, Ramachandra discloses a method for treating a subject presenting a dysregulated CD47 pathway by administering a combination of a CD47-SIRPα blocking agent and one or more anti-cancer agents and discloses the claimed CD47-SIRPα blocking agent. Ramachandra further teaches that CD47 is constitutively upregulated in AML (page 2, lines 1-2). Ramachandra thus suggests the treatment of the hematological cancer AML. Furthermore, the instant rejections are not based on Ramachandra alone but are based on a combination of Ramachandra and Sallman which, as discussed in the above grounds of rejection, suggests a combination of the claimed CD47-SIRPα blocking agent and azacitidine.
Because Applicant’s arguments are not persuasive, the instant claims are rejected for the reasons of record with modifications made to account for the claim amendments filed 11/19/2025.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
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/S.G.H./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693