DETAILED ACTION
Notice of Pre-AIA or AIA Status
This Office action details a first action on the merits for the above referenced application No. Claims 1-21 are pending in this application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Drawings
The drawings were received on 02/15/2024. These drawings are acknowledged.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 2, 4, 5, 7, 8, 11, 13, 14, 16 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Soon-Shiong et al. (WO 2018/144777).
Soon-Shiong discloses a method of treating cancer stem cells comprising administering an antibody (targeting molecules) having binding specificity towards an antigen that is specific to a mesenchymal state of a tumor stem cell (molecular markers) (abstract, claim 1 and 7). In preferred embodiment, the antigen is calreticulin, PD-L1 and/or c-MET, and the antibody is a human or humanized antibody (0016). The targeting molecule can be coupled to one or more functional moieties chemotherapeutic drug, and/or checkpoint inhibitors (PD-1) radioisotopes such that the targeting molecule can also be employed as local delivery agents for chemotherapeutic drugs, and more preferably as local delivery agents for site-specific raidoisotopic treatment using therapeutic alpha and/or beta emitters. Suitable alpha emitters include 223Ra, 225Ac, and 227Th (0034 and 0035). In one embodiment, Soon-Shiong discloses that the mesenchymal tumor cell can be targeted by contacting the mesenchymal tumor cell expressing one or more molecular markers (e.g., calreticulin, PD-L1, and c-MET) with a binding molecule (e.g., antibody, scFv fragment, TxM scaffold coupled with scFv) to the molecular markers such that the molecular marker and the binding molecule can form a protein complex (0052). The order and manner of administering the binding molecules and/or cytotoxic immune cell may vary depending on type of binding molecules, type of molecular markers, type of cytotoxic immune cells, health status of the patient, previous history of cancer treatment, and so on. Thus, in some embodiments, the binding molecules and/or cytotoxic immune cell can be administered to the patient substantially simultaneously (e.g., within 5 min, within 10 min, within 1 hour, within 2 hours, etc.). In such embodiments, it is preferred that the binding molecules and the cytotoxic immune cell are administered using the same administrating method (e.g., intratumoral injection) such that both binding molecules and cytotoxic immune cell can contact the tumor and infiltrate into the tumor almost simultaneously (0054). Most typically, the antibody will be administered in dosages between 0.01mg/kg and 150 mg/kg, or between 0.01mg/kg and 15 mg/kg, or between 0.1mg/kg and 5 mg/kg, or between lmg/kg and 10 mg/kg, for example, by weekly intravenous injection over 1-2 hours (0055). Alternatively, or additionally, one or more agents may be administered to the cancer stem cell or tumor microenvironment that up-regulates surface expression of calreticulin. For example, various anthracyclines or thapsigargin are known to increase surface expression of calreticulin (0058). Additional disclosure includes that immunogenicity may be further enhanced by administering to the cancer stem cell or tumor microenvironment a CD47 antagonist or a SHPS-1 antagonist, and/or by administering to the cancer stem cell or tumor microenvironment an agent that up- regulates surface expression of calreticulin (e.g., an anthracycline or thapsigargin).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 1-21 are rejected under 35 U.S.C. 103 as being unpatentable over Seth et al., (WO 2019027973) in view of Soon-Shiong et al. (WO 2018/144777), and Chao et al. (US 2021/0147568).
Seth discloses methods of treating a hematological malignancy, inhibiting growth and/or proliferation of a cell expressing CD38 comprising administering to a subject (human) an effective amount of composition comprising monoclonal antibody against CD38 labeled with 225Ac (abstract and claim 1). The composition may further comprise an unlabeled antibody against CD38 and/or one or more additional therapeutic agents such as chemotherapeutic agent (0013). Cancer includes solid cancer (e.g., a tumor) (0043) and solid cancer include bone cancer, pancreatic cancer, skin cancer of the head or neck, stomach cancer, carcinoma of the cervix, cancer of the esophagus, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, environmentally-induced cancers including those induced by asbestos (0045). In one embodiment, disclose that the actinium labelled monoclonal antibody can be at least 20-fold more effective at causing cell death of lymphoblast or myeloma cells than a control monoclonal antibody and the dose amount of the 225Ac labelled agent can be 20-fold lower than the dose of the control agent comprising an unlabeled monoclonal antibody (0119-0125). Seth discloses that the therapeutically effective amount of the 225Ac-labeled monoclonal antibody can be 0.1 µg/kg to 1 mg/kg body weight of the subject, wherein this protein dose can include a radioactive dose of 0.1 µCi/kg to 5 µCi/kg (0129-0130), which reads on a radiation dose. Therapeutically effective dose of the radiolabeled anti-CD38 antibody may be administered in a single dose, or as two equal fractionated doses, wherein a second dose may be administered 1 day to 10 days, such as 3-8 days or 4-7 days or 5-8 days, after the first dose (0131).
Seth fails to disclose radiolabeled calreticulin targeting agent, immune checkpoint inhibitors and a CD47 blockade such as magrolimab or lemzoparlimab in the composition.
Soon-Shiong discloses a method of treating cancer stem cells comprising administering an antibody (targeting molecules) having binding specificity towards an antigen that is specific to a mesenchymal state of a tumor stem cell (molecular markers) (abstract, claim 1 and 7). In preferred embodiment, the antigen is calreticulin, PD-L1 and/or c-MET, and the antibody is a human or humanized antibody (0016). The targeting molecule can be coupled to one or more functional moieties chemotherapeutic drug, and/or checkpoint inhibitors (PD-1) radioisotopes such that the targeting molecule can also be employed as local delivery agents for chemotherapeutic drugs, and more preferably as local delivery agents for site-specific raidoisotopic treatment using therapeutic alpha and/or beta emitters. Suitable alpha emitters include 223Ra, 225Ac, and 227Th (0034 and 0035). ). Most typically, the antibody will be administered in dosages between 0.01mg/kg and 150 mg/kg, or between 0.01mg/kg and 15 mg/kg, or between 0.1mg/kg and 5 mg/kg, or between 1mg/kg and 10 mg/kg, for example, by weekly intravenous injection over 1-2 hours (0055). Additional disclosure includes that immunogenicity may be further enhanced by administering to the cancer stem cell or tumor microenvironment a CD47 antagonist or a SHPS-1 antagonist, and/or by administering to the cancer stem cell or tumor microenvironment an agent that up- regulates surface expression of calreticulin (e.g., an anthracycline or thapsigargin).
Chao discloses methods, kits, and compositions are provided herein for determining the eligibility of a subject to receive an anti-CD47 treatment based on a presence or absence of B-cells in the subject, and subsequently treating the eligible subject with the anti-CD47 treatment alone or in combination with one or more additional agent such as an anti-CD20 antibody (abstract). In one embodiment, the method further comprises prior to administering the anti-CD47 agent and the anti-CD20 antibody to the subject, determining that the subject is a candidate for treatment given the determination that B-cells are present in the subject. In various embodiments, the determination that B-cells are present in the subject comprises determining or having determined that the subject has CD19+ B-cells (0010). The anti-CD47 agent is administered at a dose of at least 10-30, 20-30, 10, 15, 20, 30, 46, 60 or 100 mg per kg of body weight (0019). In one embodiment, discloses a method of treating a blood cancer in a subject, the method comprising: determining or having determined that B-cells are present in the subject (would read on diagnosing), wherein the determination comprises determining or having determined that the subject has at least 5 percent of CD19+ B-cells out of a total amount of lymphocytes; administering magrolimab; and administering rituximab to the subject, wherein the subject is a human subject who has previously been treated with at least two prior lines of therapy, wherein the blood cancer, e.g., B-cell hematologic malignancy, e.g., CD20+ cancer, is relapsed (0028 and FIG 1). Additional anti-CD47 agents include, without limitation, anti-CD47 mAbs (Vx-1004), anti-human CD47 mAbs (CNTO-7108), humanized anti-CD47 antibody (Hu5F9-G4; magrolimab), TTI-621, TTI-622, IMM-02, Lemzoparlimab, and SGN-CD47M (0122).
NOTE: With respect to before administering radiolabeled calreticulin targeting agent, diagnosing the subject and determining the presence, absence or extent of calretuculin-positive cells would have been obvious to one ordinary skill in the art to determine the eligibility of the subject to receive the administration of the therapeutic agents and is more likely to benefit from administration of both agents in comparison to a different subject that is determined to be ineligible. As taught by Chao the status of the blood cancer subject is used to determine 120 eligibility of the blood cancer subject. FIG. 1 depicts one embodiment where determining 120 the eligibility of the blood cancer subject includes determining 115A a presence of B-cells in the blood cancer subject. In one embodiment, if the subject is determined to have a presence of B-cells, then the subject is eligible to receive the treatment. In contrast, if the subject is determined to not have a presence of B-cells, then the subject is ineligible to receive the treatment. In some embodiments, determining 120 the eligibility of the blood cancer subject can additionally include determining whether other parts of the subject's status (e.g., subject's type of cancer, the number of prior therapies, whether the subject is relapsed or refractory to certain therapies) meet established eligibility criteria (e.g., criteria for enrolling in a clinical trial) (0453). Following administration of a labeled antibody to a subject, and after a time sufficient for binding, the biodistribution of antibody-expressing cells bound by the antibody may be visualized. The disclosed diagnostic methods may be used in combination with treatment methods. Specialists from Medical Oncology, Radiation Oncology, and Interventional Radiology evaluate each patient prior to acceptance into the therapeutic protocol. Patients are usually selected if they are candidates for treatment, and are .gtoreq.18 years of age, and have a confirmed diagnosis of a non-hematologic malignancy, with measurable unresectable disease, predominately involving the liver. Thus, patients to be treated with the antibody/drug conjugates may be selected based on biomarker expression, resulting in a patient population selected for enriched target expression rather than tumor origin or histology.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate calreticulin protein into Seth’ composition. The person of ordinary skill would have been motivated to make those modifications because Soon-Shiong teaches calreticulin is highly conserved among species and is known as a multifunctional protein acting as a major Ca2+-binding/storage protein in the lumen of endoplasmic reticulum, suggesting that it may have a role in transcription regulation and can act as an important modulator of the regulation of gene transcription by nuclear hormone receptors (0028) and reasonably would have expected success because Soon-Shiong teaches that calreticulin can inhibit the binding of the androgen receptor to its hormone-responsive DNA element and can inhibit both androgen receptor and retinoic acid receptor transcriptional activities in vivo as retinoic acid-induced neuronal differentiation.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate CD47 antibody into Seth’ composition. The person of ordinary skill would have been motivated to make those modifications because Chao teaches that CD47 has been identified as a key molecule mediating cancer cell evasion of phagocytosis by the innate immune system. CD47 appears to be an important means by which cancer cells, including cancer stem cells, overcome intrinsic expression of their prophagocytic, “eat me,” signals. The progression from normal cell to cancer cell can involve changes in genes and/or gene expression that trigger programmed cell death (PCD) and programmed cell removal (PCR) (0003) and reasonably would have expected success because it has been shown that CD47-blocking antibodies inhibit human cancer growth and metastasis by enabling phagocytosis and elimination of cancer cells from various hematologic malignancies and several solid tumors.
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGADISHWAR RAO SAMALA whose telephone number is (571)272-9927. The examiner can normally be reached Monday-Friday 9am-6pm.
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/J.R.S/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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