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 Restriction Requirement Response filed on 12/09/2025.
Claims 3, 10, 12, 15, 17-20 are drawn to non-elected species
Claims 1-6, 9-20, 22, 30 are pending in the instant application.
Claims 3, 10, 12, 15, 17-20 are withdrawn from further consideration.
Election/Restrictions
Applicant’s election without traverse of the species “non-small cell lung cancer” (claim 5), “radiation dose of 0.1 to 50uCi/kg subject body weight” (claim 9), “administered as a single dose” (claim 11), “immune checkpoint therapy” (claims 13-14) in the reply filed on 12/09/2025 is acknowledged.
Note, claims 3, 10, 12, 15, 17-20 are drawn to non-elected species.
Claim Rejections - 35 USC § 112, 1st paragraph
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 1-2, 4-6, 9, 11, 1314, 16, 22, 30 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
The instant specification fails to provide guidance that would allow the skilled artisan to practice the instant invention without resorting to undue experimentation, as discussed in the subsections set forth hereinbelow.
1. The nature of the invention, state of the prior art, relative skill of those in the art, and the predictability of the art
The claimed invention relates to treating all cancer or precancerous disorder, such as a sarcoma, a carcinoma, breast cancer, TNBC, gastric cancer, bladder cancer, cervical cancer, endometrial cancer, skin cancer, melanoma, bone cancer, osteosarcoma, stomach cancer, testicular cancer, esophageal cancer, bronchioloalveolar cancer, prostate cancer, colorectal cancer, ovarian cancer, cervical epidermoid cancer, pancreatic cancer, lung cancer, small cell lung cancer, non-small cell lung cancer, liver cancer, hepatocellular carcinoma, cholangiocarcinoma, renal cancer, renal cell carcinoma, or head and neck cancer, etc. Various cancers having various different causes are not treatable by a single method. Given the great diversity between various cancers (bladder cancer, breast cancer, lung cancer, testicular cancer, etc.), the unpredictability of treating an all cancers have a number of facets, as discussed hereinafter.
A. Treatment of Disease Type
While the state of the art is relatively high with regard to the treatment of specific diseases with a specific agent and method, it is long underdeveloped with regard to the treatment of a subject broadly, that is, general treatment, with no specific cancer combined with a specific drug therefore. In particular, there is no known “treatment” drug, that can treat, “all that ails you”. This is why the National Cancer Institute (NCI) has the extensive in vitro drug-screening program it does. As discussed by the court in In re Brana, 51 F.3d 1560 (Fed. Cir. 1995), in vitro assays are used by NCI (such as the P388 and L1210 lymphocytic leukemia tests at issue therein) to measure the potential antitumor properties of a candidate compound. Brana at 1562-63. If success is shown in this initial screening step, this demonstrates that at least one cancer type (e.g., lymphocytic leukemia) is sensitive thereto, and provides the incentive to select it for further studies to determine its usefulness as a chemotherapeutic agent against other cancer types (lung, breast, colon, etc.) Id. at 1567-68. These in vitro tests are considered reasonably correlative of success in vivo. Thus, a considerable amount of in vitro empirical testing is required, with no a priori expectation of success being present, before a candidate for even treating a specific disease, such as, cancer.
2. The breadth of the claims
The claims are very broad and encompass all types of different cancer, such as a sarcoma, a carcinoma, breast cancer, TNBC, gastric cancer, bladder cancer, cervical cancer, endometrial cancer, skin cancer, melanoma, bone cancer, osteosarcoma, stomach cancer, testicular cancer, esophageal cancer, bronchioloalveolar cancer, prostate cancer, colorectal cancer, ovarian cancer, cervical epidermoid cancer, pancreatic cancer, lung cancer, small cell lung cancer, non-small cell lung cancer, liver cancer, hepatocellular carcinoma, cholangiocarcinoma, renal cancer, renal cell carcinoma, or head and neck cancer, etc.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification does not provide any examples for treating a specific cancer. Thus, one skilled in the art would have to test every cancer using Applicant’s method to see if they are effective against a specific cancer cell.
4. The quantity of experimentation necessary
The lack of examples and adequate guidance from the specification or prior art with regard to the actual treatment fails to rebut the presumption of unpredictability present in this art. Applicants fail to provide any example or guidance and information required to ascertain which particular cancer the claimed agent will be effective against without resorting to undue experimentation.
In summary, Applicant have not provided any data on treating a specific cancer. Applicant only provided general prior art knowledge on possible treatment of different types of cancer. Thus, undue experimentations are required for one skilled in the art to use Applicant’s method to find which specific cancer is treatable and whether the method can treat all cancer.
Claim Rejections - 35 USC § 112, 2nd paragraph
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 5, 13-14, 30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5, 13-14, 30 contain the terms "TNBC", “CD47”, “PD-1, PD-L1, PD-L2, CTLA-4, TIM3, LAG3, VISTA, or A2aR”, and “p-SCN-Bn-DOTA” which is not defined by the claims. Claims must stand alone to define the invention, and should not rely on the description or the drawings to give them meaning (see Ex Parte Fressola, 27 USPQ 2d 1608). Thus, at the very least, should define "TNBC", “CD47”, “PD-1, PD-L1, PD-L2, CTLA-4, TIM3, LAG3, VISTA, or A2aR”, and “p-SCN-Bn-DOTA” by its formal chemical name; once "TNBC", “CD47”, “PD-1, PD-L1, PD-L2, CTLA-4, TIM3, LAG3, VISTA, or A2aR”, and “p-SCN-Bn-DOTA” is defined, the term "TNBC", “CD47”, “PD-1, PD-L1, PD-L2, CTLA-4, TIM3, LAG3, VISTA, or A2aR”, and “p-SCN-Bn-DOTA” may be subsequently recited.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 4-6, 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over BRAMS (US 2002/0025319) in view of GERBER et al (Tumor-specific targeting by Bavituximab, a phosphatidylserine-targeting monoclonal antibody with vascular targeting and immune modulating properties, in lung cancer xenografts. Am J Nucl Med Mol Imaging 2015;5(5):493-503).
Regarding claim 1-2, and 22, BRAMS teaches a method of treating cancer comprised of: administering to a human (see [0039]) monoclonal antibodies that specifically bind to the phospholipid phosphatidyl serine (see abstract; and [0018]), wherein the monoclonal antibody can be conjugated to radionuclides (see [0038]), for molecular targeting tumors and/or cancer cells (see abstract), such radionuclides include 90Y and 131I (see [0038]). Additional disclosures include: experiments on specific tumor cell lines (see Example 1), experiments on rabbits, mice, and monkeys (see Example II)
BRAMS does not teach using a specific type of phosphatidylserine-targeting monoclonal antibody, such as bavituximab.
GERBER teaches bavituximab is a phosphatidylserine-targeting monoclonal antibody (see title).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate bavituximab monoclonal antibody. The person of ordinary skill in the art would have been motivated to make those modifications, because reasonably would have expected success because bavituximab is a functional equivalent of phosphatidylserine-targeting monoclonal antibody used in BRAMS.
Regarding claim 4-5, BRAMS teaches treating sarcomas and other tumors and/or cancers (see [0029]).
Regarding claim 6, BRAMS teaches therapeutically effective amounts (see [0045]).
Claim(s) 1-2, 4-6, 9, 11, 13-14, 16, 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over BRAMS (US 2002/0025319) in view of GERBER et al (Tumor-specific targeting by Bavituximab, a phosphatidylserine-targeting monoclonal antibody with vascular targeting and immune modulating properties, in lung cancer xenografts. Am J Nucl Med Mol Imaging 2015;5(5):493-503) and BURAK et al (US 2021/0390789).
As discussed above, the references teach Applicant’s invention.
The references do not teach using 225AC as the radionuclide; or further using immune checkpoint therapy, such as PD-1.
BURAK teaches the prior art had known of treating sarcoma, small cell lung cancer and colorectal cancer (see [0022]) comprised of: administering in a lower effective dose (see [0007]; and [0089]) radionuclide, such as 90Y, 131I and 225Ac (see abstract; and [0167]) with checkpoint inhibitors (see abstract), such as programmed death ligand 1 (“PD-L1”; see [0178]). Additional disclosures include: single dose (see [0199]); experiment on murine colon carcinoma model (see [0219]); 400 nCi dose of 225Ac was given to mice (see [0221]); checkpoint inhibition combination therapy with radionuclide improves an immune response to tumor (see [0005]-[0007]).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate 225AC as the radionuclide. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because 90Y, 131I and 225Ac are functional equivalents of radionuclides used in cancer treatment.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using immune checkpoint therapy, such as PD-1.
The person of ordinary skill in the art would have been motivated to make those modifications, the combination therapy would improve response in treating tumors and reasonably would have expected success because the references dealt in the same field of endeavor, such as treating cancer.
The references do not specifically teach administering the dosages in the amounts claimed by Applicant. The amount of active agent dosages in a method to treat cancer is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal dosages in order to best achieve the desired results, such as effective treatment of the cancer with minimal adverse effects when treating human patients. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of dosage amounts would have been obvious at the time of Applicant's invention.
Claim(s) 1-2, 4-6, 9, 11, 13-14, 16, 22, 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over BRAMS (US 2002/0025319) in view of GERBER et al (Tumor-specific targeting by Bavituximab, a phosphatidylserine-targeting monoclonal antibody with vascular targeting and immune modulating properties, in lung cancer xenografts. Am J Nucl Med Mol Imaging 2015;5(5):493-503), BURAK et al (US 2021/0290789), and SIMON et al (US 9,603,954).
As discussed above, the references teach Applicant’s invention.
The references do not teach conjugating with p-SCN-Bn-DOTA.
SIMON teaches the prior art had known of using p-SCN-Bn-DOTA (see abstract; and col. 2, line 49-50) to conjugate a radionuclide, such as 90Y, 131I and 225Ac (see abstract; and col. 8, line 55+), to a monoclonal antibody (see abstract; and col. 9-10).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using p-SCN-Bn-DOTA to conjugate BRAMS antibody with the radionuclide. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because BRAMS teaches conjugating the antibodies to radionuclides.
Telephonic Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAKE MINH VU whose telephone number is (571)272-8148. The examiner can normally be reached Mon-Fri 9:00am-5:30pm.
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/JAKE M VU/Primary Examiner, Art Unit 1618