DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1 and 32-67 are pending.
Claims 2-31 have been cancelled.
Claims 34-55 and 59-67 have been amended.
Claims 1 and 32-67 are examined on the merits.
Claim Rejections - 35 USC § 112
3. 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.
4. Claim 1 is 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.
The claims read on methods of treating, mitigating, reducing, preventing or delaying the growth, proliferation, recurrence or metastasis of a solid cancer comprising co-administering an effective amount of radiation therapy (RT) focally-delivered to the solid cancer and an agent that inhibits binding between CD47 and SIRP.
The written description in this instant case seems to set forth a host of molecules that can be regarded as an agent that inhibits binding between CD47 and SIRP, see segment 2. spanning pages 7-28 within the Specification.
The instant application does not provide sufficient guidance as to the nexus or correlation between the structure and function of the undefined host of agents able to inhibit binding between CD47 and SIRP that places the skilled artisan in possession of the relevant identifying characteristics of a genus of agents thereof commensurate in scope with the claimed invention.
In Abbvie v. Centocor (Fed. Cir. 2014), the Court held that a disclosure of many different antibodies (in that case neutralizing antibodies to IL-12 with a particular binding affinity) was not enough to support the genus of all IL-12 neutralizing antibodies because the disclosed antibodies were very closely related to each other in structure and were not representative of the full diversity of the genus. The Court further noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
“A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus.” See AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69.
Vas-Cath Inc. V Mahurkar, 19 U5PQ2d 1111, clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 115).
The skilled artisan cannot envision the detailed structure of the encompassed agents and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and a reference to a potential method of isolating it. The polypeptide itself is required. See Fiers v. Revel, 25 U5PQ 2d 1601 at 1606 (CAFC1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts. 18 U5PQ2d 1016.
Furthermore, In The Reagents of the University of California v. Eli Lilly (43 U5PQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that while Applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a representative number of DNA molecules, usually defined by a nucleotide sequence, falling within the scope of the claimed genus. At section B(l), the court states that "An adequate written description of a DNA...'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".
At the time the application was filed Applicants seem to not be in possession of all agents that inhibit binding between CD47 and SIRP. The specification does not evidence the possession of all binding molecules that are undefined and uncharacterized falling within the potentially large genus to establish possession. No corollary nexus has been established between structure and function.
The USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018. See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following.
“In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”.
There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the agents that specifically inhibit binding between CD47 and SIRP essential to the claimed invention to demonstrate possession that fulfill the requirements of a structure-function relationships of written description. Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
“When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.” See Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), the following is noted.
To show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358).
The instant disclosure, including the claims fail to disclose a representative number of species falling with the scope of the genus and/or structural common to the members of the genus so the one of skill in the art can visualize or recognize the members of the genus of agents that inhibit binding between CD47 and SIRP. These agents include a host of molecules as set forth in the Specification, see segment 2. Spanning pages 7-28. Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361).
An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
Here, Applicant’s claim by virtue of the breath of the broad term, agent includes molecules that encompass various structural, specificities and functional attributes to fulfill the requirements of a structure-function relationships of written description, but does not describe the structure-identifying information about the agent, nor describe a representative number of species falling with the scope of the genus or structural common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus of the actual agent.
A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that exhibit this functional property.
The specification does not evidence the possession of all agents that are undefined and uncharacterized, falling within the potentially large genus to establish possession. Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 U5PQ2d 1398.
The full breadth of the claims do not meet the written description provision of 35 U.S.C. 112, first paragraph.
Claim Rejections - 35 USC § 102
5. 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)(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.
6. Claim(s) 1, 32-44, 48, 49, 51-62 and 65-67 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Sage et al., WO 2022/020341 A1 (effective filing date, 20 August 2020/ IDS reference BB submitted July 31, 2024). Sage discloses treating human solid cancers and metastatic cancer with a combinatorial therapeutic regimen including an effective dose or series of doses of a CD47 blocking agent, i.e. an agent that blocks the interaction between CD47 and SIRPα and localized radiation therapy (RT) to evoke both, an abscopal effect and synergistic effect, see abstract; page 1, section 0003; page 2, sections 0008-0011; page 9, section 0036; page 17, section 0069; section 0071 bridging pages 17 and 18; page 19, section 0078; page 34, section 00134; and page 45, claims 1-12 and 14.
Sage “…provides methods for reducing growth of cancer cells, including metastatic cancer cells, through radiation therapy combined with a CD47 blocking agent, e.g. soluble SIRPa monomer or multimer, an anti-CD47 antibody, an anti-SIRPa antibody, small molecule, etc.”, page 25, section 00102. The agent that inhibits binding between CD47 and SIRPα may be an anti-CD47 antibody is magrolimab also known as hu5F9-G4, page 3, section 0012; page 12, section 0049; and page 45.
“[A] combination therapy comprising radiation therapy in combination with CD47 blockade increases an abscopal effect, relative to radiation therapy alone. The abscopal effect can result in a reduction in tumor volume of a non-irradiated tumor mass. In some embodiments, combination therapy comprising radiation therapy in combination with CD47 blockade increases the abscopal effect such that there is about a 10% reduction in tumor volume of a non-irradiated tumor mass, relative to radiation therapy alone. In some embodiments, there is a 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, 90-100%, or greater than 100% reduction in tumor volume of the non-irradiated tumor, relative to radiation therapy alone.”, see page 25, section 00104.
“Synergistic combinations may provide for a therapeutic effect that is comparable to the effectiveness of a monotherapy, i.e. the individual components of the combination, while reducing adverse side effects, e.g. damage to non-targeted tissues, immune status, and other clinical indicia. Alternatively synergistic combinations may provide for an improved effectiveness when compared to the effectiveness of a monotherapy, i.e. the individual components of the combination, which effect may be measured by decreased metastasis, total tumor cell number; length of time to relapse; and other indicia of patient health.”, see page 9, section 0036. Hence, it is within the Examiner’s purview, the wherein clauses set forth in claims 56-58 reading on increased and enhanced elimination of cancer cells, reduced cancer cell growth and tumor burden are met when the combination of therapeutic agents are administered versus the magrolimab or the focally-delivered RT alone.
“The CD47 blocking agent can be administered prior to or during the course of radiation... In some embodiments, e.g. where radiation is delivered as a course of therapy over multiple days, the CD47 [blocking] agent may be administered on days alternating with the radiation therapy, as desired for the dosage. For example, the CD47 blocking agent may be delivered every other day, every third day, twice a week, once a week, etc., one days that are the same or different as the radiation therapy days.”, see page 3, section 0015. “The CD47 blocking agent may be administered…on alternative days, before…delivery of radiation, etc., usually not more than 1 , not more than 2, not more than 3 days before or after radiation.“, see page 26, section 00110.
“The subject methods include a step of administering a priming dose to the subject, followed by a step of administering a therapeutically effective dose of an anti-CD47 agent to the subject.”, see page 27, section 00112. “The specific appropriate priming dose of an anti-CD47 agent can vary depending on the nature of the agent used and on numerous subject-specific factors (e.g., age, weight, etc.). Examples of suitable priming doses of an anti-CD47 agent include from about 0.5 mg/kg to…about 5 mg/kg.”, see page 27, section 00114. Thereafter, a maintenance dose or escalating dosages can be administered ranging from about 5 mg/kg to about 30 mg/kg, see sections 00117-0019 spanning pages 28 and 29.
“[T]he CD47 blocking agent may be delivered every other day, every third day, twice a week, once a week, etc., one days that are the same or different as the radiation therapy days.”, see section 0015.” “The administration of a therapeutically effective dose of an anti-CD47 agent can be achieved in a number of different ways. In some cases, two or more therapeutically effective doses are administered after a primer agent is administered. Suitable administration of a therapeutically effective dose can entail administration of a single dose, or can entail administration of doses daily, semi-weekly, weekly, once every two weeks, once a month, annually, etc. In some cases, a therapeutically effective dose is administered as two or more doses of escalating concentration (i.e., increasing doses), where (i) all of the doses are therapeutic doses, or where (ii) a sub-therapeutic dose (or two or more sub-therapeutic doses) is initially given and therapeutic doses are achieved by said escalation. As one non-limiting example to illustrate escalating concentration (i.e., increasing doses), a therapeutically effective dose can be administered weekly, beginning with a sub-therapeutic dose (e.g., a dose of 5 mg/kg), and each subsequent dose can be increased by a particular increment (e.g., by 5 mg/kg), or by variable increments, until a therapeutic dose (e.g., 30 mg/kg) is reached, at which point administration may cease or may continue (e.g., continued therapeutic doses, e.g., doses of 30 mg/kg). As another non-limiting example to illustrate escalating concentration (i.e., increasing doses), a therapeutically effective dose can be administered weekly, beginning with a therapeutic dose (e.g., a dose of 10 mg/kg), and each subsequent dose can be increased by a particular increment (e.g., by 10 mg/kg), or by variable increments, until a therapeutic dose (e.g., 30 mg/kg, 100 mg/ml, etc.) is reached, at which point administration may cease or may continue (e.g., continued therapeutic doses, e.g., doses of 30 mg/kg, 100 mg/ml, etc.). In some embodiments, administration of a therapeutically effective dose can be a continuous infusion and the dose can be altered (e.g., escalated) over time.”, see section 0019 spanning pages 28 and 29.
The disclosed combinatorial therapeutic regimen may be combined with immune checkpoint inhibitor (ICI), for instance programmed death 1 receptor (PD-1), see page 3, section 0016. Term, “may” inherently implied that the said regimen may not be combined with an ICI.
Cancers amenable to the disclosed combinatorial treatment include squamous cell carcinoma, lung cancer, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), as well as “…bladder cancer, …brain cancers, …breast cancer, …colon and rectum cancer, …esophagus cancer, Ewing's family of tumors (e.g. Ewing's sarcoma), eye cancer, gallbladder cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, gestational trophoblastic disease, hairy cell leukemia, Hodgkin's lymphoma, Kaposi's sarcoma, kidney [renal] cancer, …liver cancer, lung cancer, lung carcinoid tumors, …male breast cancer, …nasopharyngeal cancer, …osteosarcoma, ovarian cancer, pancreatic cancer, …prostate cancer, …sarcomas, melanoma skin cancer, non-melanoma skin cancers, stomach cancer, testicular cancer, …uterine cancer (e.g. uterine sarcoma), transitional cell carcinoma, …squamous cell or epidermoid carcinoma, … head and neck cancers amongst other cancers, see page 2, section 0010; section 0071 bridging pages 17 and 18.
“SCLC of any stage is typically initially responsive to treatment, but responses are usually short-lived... Surgery generally plays no role in treatment of SCLC, although it may be curative in the rare patient who has a small focal tumor without spread (such as a solitary pulmonary nodule) who underwent surgical resection before the tumor was identified as SCLC. Chemotherapy regimens of etoposide and a platinum compound (either cisplatin or carboplatin) are commonly used,”, see page 25, section 00101.
The “don’t-eat-me” molecule, CD47 is broadly expressed on the surface a variety of human neoplasms, including SCLC cells, page 1, section 0005; and page 34, section 00134.
“In some embodiments the radiation therapy is external beam radiation therapy [EBRT or brachytherapy (internal radiation therapy], including without limitation stereotactic body radiation therapy (SBRT); three-dimensional conformal radiation therapy (3D-CRT); intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT).”, see page 3, section 0014; and page 26, section 00106.
“A number of fractionation schemes can be used to deliver radiation.”, see page 26, section 00107. The radiation may be delivered by a hypofractionated (higher dose per fraction and fewer fractions) scheme, as well as alternative fractionated schemes over multiple administrations, see page 3, section 0014; page 26, sections 00107-00109; and pages 45 and 46.
“[A] clinician can determine the maximum safe dose for an individual,” for any of the therapeutic compositions that “…may be administered using any medically appropriate procedure”, see section 00126 bridging pages 30 and 31.
Claim Rejections - 35 USC § 103
7. 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.
8. Claim(s) 1 and 32-67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sage et al., WO 2022/020341 A1 (effective filing date, 20 August 2020/ IDS reference BB submitted July 31, 2024), and further in view of Basciano et al., US 2021/0030739 (effective filing date September 28, 2018). Sage discloses treating human solid cancers and metastatic cancer with a combinatorial therapeutic regimen including an effective dose or series of doses of a CD47 blocking agent, i.e. an agent that blocks the interaction between CD47 and SIRPα and localized radiation therapy (RT) to evoke both, an abscopal effect and synergistic effect, see abstract; page 1, section 0003; page 2, sections 0008-0011; page 9, section 0036; page 17, section 0069; section 0071 bridging pages 17 and 18; page 19, section 0078; page 34, section 00134; and page 45, claims 1-12 and 14.
Sage “…provides methods for reducing growth of cancer cells, including metastatic cancer cells, through radiation therapy combined with a CD47 blocking agent, e.g. soluble SIRPa monomer or multimer, an anti-CD47 antibody, an anti-SIRPa antibody, small molecule, etc.”, page 25, section 00102. The agent that inhibits binding between CD47 and SIRPα may be an anti-CD47 antibody is magrolimab also known as hu5F9-G4, page 3, section 0012; page 12, section 0049; and page 45.
“[A] combination therapy comprising radiation therapy in combination with CD47 blockade increases an abscopal effect, relative to radiation therapy alone. The abscopal effect can result in a reduction in tumor volume of a non-irradiated tumor mass. In some embodiments, combination therapy comprising radiation therapy in combination with CD47 blockade increases the abscopal effect such that there is about a 10% reduction in tumor volume of a non-irradiated tumor mass, relative to radiation therapy alone. In some embodiments, there is a 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, 90-100%, or greater than 100% reduction in tumor volume of the non-irradiated tumor, relative to radiation therapy alone.”, see page 25, section 00104.
“Synergistic combinations may provide for a therapeutic effect that is comparable to the effectiveness of a monotherapy, i.e. the individual components of the combination, while reducing adverse side effects, e.g. damage to non-targeted tissues, immune status, and other clinical indicia. Alternatively synergistic combinations may provide for an improved effectiveness when compared to the effectiveness of a monotherapy, i.e. the individual components of the combination, which effect may be measured by decreased metastasis, total tumor cell number; length of time to relapse; and other indicia of patient health.”, see page 9, section 0036. Hence, it is within the Examiner’s purview, the wherein clauses set forth in claims 56-58 reading on increased and enhanced elimination of cancer cells, reduced cancer cell growth and tumor burden are met when the combination of therapeutic agents are administered versus the magrolimab or the focally-delivered RT alone.
“The CD47 blocking agent can be administered prior to or during the course of radiation... In some embodiments, e.g. where radiation is delivered as a course of therapy over multiple days, the CD47 [blocking] agent may be administered on days alternating with the radiation therapy, as desired for the dosage. For example, the CD47 blocking agent may be delivered every other day, every third day, twice a week, once a week, etc., one days that are the same or different as the radiation therapy days.”, see page 3, section 0015. “The CD47 blocking agent may be administered…on alternative days, before…delivery of radiation, etc., usually not more than 1, not more than 2, not more than 3 days before or after radiation.“, see page 26, section 00110.
“The subject methods include a step of administering a priming dose to the subject, followed by a step of administering a therapeutically effective dose of an anti-CD47 agent to the subject.”, see page 27, section 00112. “The specific appropriate priming dose of an anti-CD47 agent can vary depending on the nature of the agent used and on numerous subject-specific factors (e.g., age, weight, etc.). Examples of suitable priming doses of an anti-CD47 agent include from about 0.5 mg/kg to…about 5 mg/kg.”, see page 27, section 00114. Thereafter, a maintenance dose or escalating dosages can be administered ranging from about 5 mg/kg to about 30 mg/kg, see sections 00117-0019 spanning pages 28 and 29.
“[T]he CD47 blocking agent may be delivered every other day, every third day, twice a week, once a week, etc., one days that are the same or different as the radiation therapy days.”, see section 0015.” “The administration of a therapeutically effective dose of an anti-CD47 agent can be achieved in a number of different ways. In some cases, two or more therapeutically effective doses are administered after a primer agent is administered. Suitable administration of a therapeutically effective dose can entail administration of a single dose, or can entail administration of doses daily, semi-weekly, weekly, once every two weeks, once a month, annually, etc. In some cases, a therapeutically effective dose is administered as two or more doses of escalating concentration (i.e., increasing doses), where (i) all of the doses are therapeutic doses, or where (ii) a sub-therapeutic dose (or two or more sub-therapeutic doses) is initially given and therapeutic doses are achieved by said escalation. As one non-limiting example to illustrate escalating concentration (i.e., increasing doses), a therapeutically effective dose can be administered weekly, beginning with a sub-therapeutic dose (e.g., a dose of 5 mg/kg), and each subsequent dose can be increased by a particular increment (e.g., by 5 mg/kg), or by variable increments, until a therapeutic dose (e.g., 30 mg/kg) is reached, at which point administration may cease or may continue (e.g., continued therapeutic doses, e.g., doses of 30 mg/kg). As another non-limiting example to illustrate escalating concentration (i.e., increasing doses), a therapeutically effective dose can be administered weekly, beginning with a therapeutic dose (e.g., a dose of 10 mg/kg), and each subsequent dose can be increased by a particular increment (e.g., by 10 mg/kg), or by variable increments, until a therapeutic dose (e.g., 30 mg/kg, 100 mg/ml, etc.) is reached, at which point administration may cease or may continue (e.g., continued therapeutic doses, e.g., doses of 30 mg/kg, 100 mg/ml, etc.). In some embodiments, administration of a therapeutically effective dose can be a continuous infusion and the dose can be altered (e.g., escalated) over time.”, see section 0019 spanning pages 28 and 29.
The disclosed combinatorial therapeutic regimen may be combined with immune checkpoint inhibitor (ICI), for instance programmed death 1 receptor (PD-1), see page 3, section 0016. Term, “may” inherently implied that the said regimen may not be combined with an ICI.
Cancers amenable to the disclosed combinatorial treatment include squamous cell carcinoma, lung cancer, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), as well as “…bladder cancer, …brain cancers, …breast cancer, …colon and rectum cancer, …esophagus cancer, Ewing's family of tumors (e.g. Ewing's sarcoma), eye cancer, gallbladder cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, gestational trophoblastic disease, hairy cell leukemia, Hodgkin's lymphoma, Kaposi's sarcoma, kidney [renal] cancer, …liver cancer, lung cancer, lung carcinoid tumors, …male breast cancer, …nasopharyngeal cancer, …osteosarcoma, ovarian cancer, pancreatic cancer, …prostate cancer, …sarcomas, melanoma skin cancer, non-melanoma skin cancers, stomach cancer, testicular cancer, …uterine cancer (e.g. uterine sarcoma), transitional cell carcinoma, …squamous cell or epidermoid carcinoma, … head and neck cancers amongst other cancers, see page 2, section 0010; section 0071 bridging pages 17 and 18.
“SCLC of any stage is typically initially responsive to treatment, but responses are usually short-lived... Surgery generally plays no role in treatment of SCLC, although it may be curative in the rare patient who has a small focal tumor without spread (such as a solitary pulmonary nodule) who underwent surgical resection before the tumor was identified as SCLC. Chemotherapy regimens of etoposide and a platinum compound (either cisplatin or carboplatin) are commonly used,”, see page 25, section 00101.
The “don’t-eat-me” molecule, CD47 is broadly expressed on the surface a variety of human neoplasms, including SCLC cells, page 1, section 0005; and page 34, section 00134.
“In some embodiments the radiation therapy is external beam radiation therapy [EBRT or brachytherapy (internal radiation therapy], including without limitation stereotactic body radiation therapy (SBRT); three-dimensional conformal radiation therapy (3D-CRT); intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT).”, see page 3, section 0014; and page 26, section 00106.
“A number of fractionation schemes can be used to deliver radiation.”, see page 26, section 00107. The radiation may be delivered by a hypofractionated (higher dose per fraction and fewer fractions) scheme, as well as alternative fractionated schemes over multiple administrations, see page 3, section 0014; page 26, sections 00107-00109; and pages 45 and 46.
“[A] clinician can determine the maximum safe dose for an individual,” for any of the therapeutic compositions that “…may be administered using any medically appropriate procedure”, see section 00126 bridging pages 30 and 31.
Sage does not explicitly teach the magrolimab is administered at a priming dose of 1 mg/kg at week one; administered weekly (Q1W) at a dose of 20 mg/kg, 30 mg/kg from week 2 to week 5; and administered every 3 weeks (Q3W) at a dose of 45mg, 60 mg/kg for week 6 and thereafter.
Sage does not teach the claimed method, wherein the cancer is unresectable, locally advanced and the subject is treatment naïve and the cancer has progressed after the subject received a course of an immune checkpoint inhibitor or platinum coordination complex therapy.
However, Sage does teach priming dose(s) of an anti-CD47 agent ranging from about 0.5 mg/kg to 5 mg/kg with additional dosages ranging from about 5 mg/kg to 50 mg/kg, wherein the dose can be administered on a weekly dosage schedule, see sections 00114 on page 27; page 28, section 00116; section 00119 bridging pages 28 and 29; and page 30, section 00124.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention was made to administer the magrolimab at the cited dosages and time points within in instant claims, 63 and 64 with a reasonable expectation of success by teachings well known and noted herein that dosages of any pharmaceutical composition may be adjusted and optimized.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings well known
in the art and herein, “[a] competent clinician will be able to determine an effective amount of a therapeutic composition to administer to a patient to retard the growth and promote the death of tumor cells.”, see section 00126 on page 31.
Basciano teaches methods of treating cancer, patient populations, experimental treatment arms and assessments that monitor patient response to treatment and aid in clinical decisions. An investigator and/or physician may implement the Response Evaluation Criteria in Solid Tumors (RECIST) including RECIST 1.1, an art known unidimensional method, which is able to measure/determine the overall tumor burden or volume taught in Sage, see page 10, section 0106; page 11, section 0134. The patient populations included those with advanced (metastatic and/or unresectable) malignancies, locally advanced, treatment naïve, as well as patients that “…have received, and then progressed or been intolerant to standard treatment regimen”, see page 10, section 0098; page 11, sections 0134 and 0135; page 13, section 0181-0184; and page 16, sections 0263-0265. It is art known standard cancer treatment regimens comprise surgery, chemotherapy, radiotherapy, immunotherapy and targeted therapy. Immune checkpoint inhibitor is immunotherapy and chemotherapy includes platinum coordination complex therapy (cisplatin and carboplatin), see page 9, section 0092.
It would have been obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to combine of teachings of
Sage and Basciano to assess specific patient populations with quantitative analysis and evaluate tumor response to guide the person skilled in the art, investigator and/or physician to clinical practices beneficial to specific patients, see both references in their entirety.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by the teachings of both, Sage and Basciano, as well as what is known in the art, it is important to design studies and cancer treatments that are safe and allow those in the art to arrive at a consistent analysis of cancer and efficacy assessments that will benefit cancer patients, see both references in their entirety.
Conclusion
9. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached 8AM-8PM, Monday through Friday.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
17 February 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643