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 and 20-37 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/09/2023 was noted and the submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 03/09/2023. These drawings are acknowledged.
Claim Rejections - 35 USC § 112
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 22-25 recites the limitation "the PARPi" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 30 recites the limitation "the product composition" in line 1. There is insufficient antecedent basis for this limitation in the claim. It is noted that claim 1 recites “product combination” and not product combination.
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)(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.
Claim(s) 1, 20, 22, 23, 25, 26, and 31-37 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Domankevich et al. (WO 2020/089819).
Domankevich discloses a method of treating a patient with tumor comprising administering intra-tumoral alpha-emitter radiotherapy substance (includes alpha-emitting radionuclide or atoms or their daughter radionuclides) and additional treatment comprising administering DNA repair inhibitors (page 2, line 13-25 and page 15 line 25-33). The DNA repair inhibitors include ATR inhibitors, ATM/ATR inhibitors and/or PARP inhibitors such as Olaparib, Talazoparib (page 15 line 25-33). Administering the substance together with a delivery agent comprising a lipid-based delivery agent, a solid nanoparticle such as a solid lipid nanoparticle and/or a solid nanoparticle (page 2 line 30+). In one embodiment, the alpha-emitter radiation treatment optionally includes brachytherapy, by insertion of seeds carrying alpha emitting atoms, such as Radium-224 or Radium-223, into the tumor (page 12 line 1-3). The alpha-emitter radiation treatment was performed by a 70 kBq seed of radium-224 (page 17 line 33-35). Exemplary tumor that can be treated include tumors of the colorectal cancer, liver cancer, bladder cancer, ovarian cancer, small-cell and non-small cell lung cancer, breast cancer, astrocytoma, ganglioblastoma, melanoma (page 7 and 8). Additional disclosure includes that the timing of providing the additional treatment is optionally selected according to the specific type of the treatment, for example, checkpoint inhibitors , when provide, are administered during or after the alpha-emitter radiotherapy, possibly even 3 days or even a week after beginning the alpha-emitter radiotherapy and/or after completion of the radiotherapy.
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 and 20-37 are rejected under 35 U.S.C. 103 as being unpatentable over Larsen et al. (US 9,539,346) in view of Cuthbertson (US 2020/0016283).
Larsen discloses pharmaceutical composition comprising one, more particles or a suspension of same or different particles comprising a degradable compound and an alpha emitting radionuclide and/or a radionuclide generating alpha emitting daughter (reads of progeny of alpha emitting radionuclide) beneficial for use in the treatment of cancer (abstract). In one embodiment discloses the radionuclide selected from the group consisting of 224Ra, 212Bi, 212Pb, 223Ra, 225Ra, 225Ac, 213Bi, 211At, 227Th. The degradable compound selected from the group consisting of CaCO3, PEG modified CaCO3, protein modified CaCO3, carbohydrate modified CaCO3, lipid modified CaCO3, vitamin modified CaCO3, organic compound modified CaCO3, polymer modified CaCO3 and/or inorganic crystal modified CaCO3. The size of the particle from 1 nm to 500 μm ( Col. 2 line 13-25). In one embodiment, discloses the pharmaceutical composition prepared with an amount of radionuclide that is 50 MBq to 100 GBq suitable for multidose industrial scale production (Col. 2 line 35-41). Discloses a pharmaceutical composition comprising diluent, carrier, surfactant, and/or excipient and composition a particle suspension comprising monodisperse or polydisperse particles labeled with an alpha emitting radionuclide and/or a radionuclide generating alpha emitting daughter (Col. 2 line 43-46). The particle comprises one or more compounds selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a radioimmunoconjugate, an immunoconjugate, a chelate antibody conjugate, vitamins including folate and folate derivatives, peptides, minibodies, and affibodies (Col. 6 line 8-14). In one embodiment, discloses method of treating cancer in a human in need thereof, comprising administering to the human one or more therapeutic particles, wherein the one or more particles comprise: a degradable compound comprising CaCO3; and an alpha emitting 224Ra radionuclide; and daughter radionuclides of the alpha emitting 224Ra radionuclide, wherein the daughter radionuclides are 220Rn, 216Po, and 212Pb (Col. 8 line 51-55 and claim 8). Additional disclosure includes that pharmaceutical composition us used in the treatment the cancer selected from the group consisting of intreaperitonial cancers, intracranial cancers, pleural cancers, bladder cancers, cardiac cancers, and cancers in the subarachnoid cavity, metastatic cancer, lung cancer, ovarian cancer, colorectal cancer, stomach cancer, pancreatic cancer, breast cancer, neoplastic meningitis, peritoneal cancer, pleural effusion, malignant mesothelioma, breast cancer, sarcomas, brain cancers like glioblastoma and astrocytoma, bladder cancer, and liver cancer.
Larsen fails to disclose DNA repair inhibitor in the composition.
Cuthbertson discloses a method of combination therapy comprising administration of a tissue-targeting radio-pharmaceutical (alpha-emitter) and a DNA-repair inhibitor. The method may be used in the treatment of hyperplastic or neoplastic disease, such as a carcinoma, sarcoma, myeloma, leukemia, lymphoma or mixed type cancer (abstract). In one embodiment, the DNA-repair inhibitor is an inhibitor of a protein selected from PARP1, ATR, ATM and DNA-PK, preferably ATR (0015). Examples of preferable FDA-approved PARP inhibitors include Olaparib and Rucaparib, Niraparib, Iniparib, Talazoparib, Veliparib (0088). The tissue-targeting radiopharmaceutical and the DNA repair inhibitor may be administered sequentially in either order, or simultaneously. In a further particular embodiment, the tissue-targeting pharmaceutical is administered before the DNA-repair inhibitor. In this case, the DNA-repair inhibitor is preferably administered at least two days after administration of the tissue-targeting radiopharmaceutical, such as 2-15 days, preferably 4-10 days, more preferably 6-8 days. For example, the DNA repair inhibitor may be administered 7 days after the administration of the tissue-targeting radiopharmaceutical (0093). In one embodiment, discloses a method of treating a hyperplastic or neoplastic disease, such as a carcinoma, sarcoma, myeloma, leukemia, lymphoma or mixed type cancer, including Non-Hodgkin's Lymphoma or B-cell neoplasms, breast, colorectal, endometrial, gastric, acute myeloid leukemia, prostate or brain, mesothelioma, ovarian, lung or pancreatic cancer, comprising administering to an animal, preferably a mammal, e.g. human, effective amounts of the components of a combination therapy (0023). Additional disclosure includes that the combination therapy is thus more effective than the use of the tissue targeting radiopharmaceutical alone or the DNA repair inhibitor alone and the effect of the combination is greater than the sum of the effects of the components used individually.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate small molecules of DNA repair inhibitor into Larsen’s composition. The person of ordinary skill in the art would have been motivated to make those modifications because Cuthbertson teaches that combinations of targeted radiopharmaceuticals with small molecule DNA-repair inhibitors can improve the therapeutic efficiency of radiopharmaceuticals. In particular, the combination treatment of may result in an additive, super-additive or synergistic interaction between a radiopharmaceutical and at least one from a range of DNA repair inhibitors and may be employed against various targets and cancer cell lines and a key advantage of the combination therapy is the synergistic effect of the DNA repair inhibitor and the tissue-targeting radiopharmaceutical (0008) and reasonably would have expected success because the DNA repair inhibitor and the tissue-targeting radiopharmaceutical work in tandem to increase the effectiveness in treatment and combination therapy is thus more effective than the use of the tissue targeting radiopharmaceutical alone or the DNA repair inhibitor alone and the effect of the combination is greater than the sum of the effects of the components used individually.
Conclusion
No claims are allowed at this time.
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/J.R.S/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618