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 .
Receipt is acknowledged of Applicant’s Amendments and Arguments filed on 05/12/2026.
Claims 1 and 23 have been amended.
Claims 22-25 have been cancelled. Accordingly, claims 1, 21, and 26-37 are pending and presented for examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/12/2026 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.
Any previous rejections and/or objections not reiterated herein have been withdrawn view of amendments filed on 05/12/2026. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
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, and 26-37 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) are maintained for reasons of record in the previous office action mailed on 11/13/2025.
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 poly (ADP-ribose) polymerase inhibitor (PARPi) Niraparib 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 PARPi, 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.
Applicant’s arguments filed on 05/12/2026 have been fully considered but they are not persuasive. Applicant argues that an evaluation of the combination indices of paired combinations at concentrations similar to and less than the single agent ICso revealed that the pharmacodynamic interactions of the pairs were mainly synergistic. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., paired combinations at concentrations of radium-224 with DNA repair inhibitor Niraparib) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues that the claimed methods of using the required product combination unexpectedly demonstrated synergistic results. In order to overcome a prima facie case of obviousness, it is incumbent upon the Applicant to provide comparative test evidence that demonstrates unexpected superiority of the claimed compositions versus the closest prior art compositions, and not simply an advantage predictable from the prior art. See In re Chapman, 148 USPQ 711, 715 (CCPA, 1966). Moreover, such proffered comparisons must be commensurate in scope with the breadth of the claims. See In re Clemens, 206 USPQ 289, 296 (CCPA, 1980) and In re Coleman, 205 USPQ 1172, 1175 (CCPA 1980). Prior art relates not only to structurally similar compositions but also a method of combination therapy comprising administration of a tissue-targeting radio-pharmaceutical (alpha-emitter) and a PARPi 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. The method is routine to a person skilled in the art, with the result that the claimed subject matter can ultimately be classified as non-inventive. In the absence of comparative data or other suitable information demonstrating an unexpected or surprising effect of the present product combination comprising radium-24 with DNA repair inhibitor over prior art, the problem addressed by the application can only be considered to be providing alternative compounds with the corresponding named properties. In view of documents prior art, a person skilled in the art would have arrived at the present compounds without further inventive skill, and would have expected that said compounds also have the same qualitative properties as the compounds of the prior art.
Conclusion
No claims are allowed at this time.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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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