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 .
Detailed Action
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9 September 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. See attached copy of PTO-1449.
Status of Application
2. Applicants’ arguments/remarks filed 9 September 2025 are acknowledged. Claims 1, 3-13, 17, and 20 are currently pending. Claims 2, 14-16, and 18-19 have been cancelled. Claim 1 has been amended. Claims 1, 3-13, 17, and 20 are examined on the merits within.
New Rejections
Claim Rejections – 35 U.S.C. 112(a) Scope of Enablement
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. Claims 1, 3-13, 17, and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for reducing or mitigating, does not reasonably provide enablement for preventing development of one or more deleterious effects of exposure to mixed filed radiation. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth 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 nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
Nature of the invention: The claimed invention is a method of reducing, mitigating or preventing development of one or more deleterious effects of exposure to mixed field radiation.
The state of the prior art: There are no methods described in the prior art or in the specification to completely prevent deleterious effects of exposure to mixed field radiation.
The relative skill of those in the art: The relative skill of those in the pharmaceutical development and medical treatment arts is high, requiring advanced education and training.
The predictability or unpredictability of the art/breadth of the claims: The instant claimed invention is highly unpredictable since one skilled in the art would recognize the breadth of the instant claims encompass prevention of diseases and conditions caused by various forms of radiation. The specification states that radiation in nature is typically encountered as a mixed field that contains multiple types of radiation rather than as a single beam exposure type commonly created by man. See page 8. Thus the breadth of the claims include 100% prevention of development of any cardiovascular disease, tissue fibrosis, inflammation or neurodegenerative conditions caused by radiation in nature.
The amount of direction or guidance presented, and the presence or absence of working examples: It has been established that “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970). There is minimal discussion in the specification that would indicate that the claimed invention prevents development of all types of cardiovascular diseases, tissue fibrosis, inflammation and neurodegenerative conditions caused by any type of mixed field radiation which is found in nature. Example 2 is directed to the protective effects of genistein against mixed field radiation but only tests a mixed field of 32% neutrons and 68% gamma radiation. This does not encompass all types of mixed field radiation. The data shows the genistein treated cells exhibited increased survival after exposure to multiple doses of MF radiation. Although this shows a protective effect of mitigating damage, the data does not show or support 100% prevention of the formation of development of all types of cardiovascular diseases, tissue fibrosis, inflammation and neurodegenerative conditions caused by any type of mixed field radiation.
The quantity of experimentation necessary: Given that the instant claims encompass complete prevention of development of all types of cardiovascular diseases, tissue fibrosis, inflammation and neurodegenerative conditions caused by any type of mixed field radiation, one skilled in the art would undertake a novel and extensive research program to show that the instant claimed compositions reduce the risk of developing any of the claimed conditions from any combinations of radiation, which are usually found in nature. There are no teachings in the prior art to completely prevent such dysfunctions. Applicant fails to provide information sufficient to practice the claimed invention, absent undue experimentation. The burden of enabling the prevention of a disease would be much greater than that of enabling the reduction or mitigation of such conditions. The specification does not provide guidance as to how one skilled in the art would accomplish the objective of preventing such conditions, or how a patient could be kept from ever being susceptible to these conditions. There is no guidance provided as to a specific protocol to be utilized in order to show the efficacy of the presently claimed active ingredients for preventing the above claimed conditions, thereby presenting an undue burden of unpredictable experimentation necessary to practice the claimed invention.
Genentech, 108 F.3d at 1366, states, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors as discussed above, particularly the unpredictability of the art and the breadth of the claims, Applicants fail to provide information sufficient to practice the claimed invention for a method of prevention of development of cardiovascular diseases, tissue fibrosis, inflammation and neurodegenerative conditions caused by mixed field radiation
Maintained Rejections
Claim Rejection – 35 U.S.C. 103
5. 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.
6. Claim(s) 1, 3-13, 17, and 20 is/are again rejected under 35 U.S.C. 103 as being unpatentable over Elder, Jr. et al. (U.S. Patent No. 8,551,530) as evidenced by Atomic Archive and The Cleveland Clinic.
Regarding instant claims 1, 4, and 6, Elder, Jr. et al. teach formulations of nanoparticulate genistein. See abstract. Elder, Jr. et al. teach a method of treating acute radiation syndrome comprising identifying a subject that has experienced exposure to radiation of at least 0.3 Gray or 30 rads and administering a therapeutically effective amount of a genistein formulation comprising nanoparticulate genistein, one or more pharmaceutically acceptable excipients including polyvinylpyrrolidone, wherein the nanoparticulate genistein exhibits a D(0.50) of 0.5µm or less, wherein genistein is administered in an amount between 250 and 500 mg/ml. See claim 1. Elder, Jr et al. also teach genistein administered prior to, during and/or after exposure to radiation, may be used to eliminate or reduce the severity of the deleterious cellular effects caused by exposure to ionizing radiation resulting from nuclear explosion, a spill of radioactive material, close proximity to radioactive material, cancer radiation therapy, diagnostic tests that utilize radiation, and the like. See column 12, lines 39-55. Nuclear explosions comprise mixed radiation such as gamma, neutron, and ionizing as evidenced by Atomic Archive. Example 5 shows a twice daily administration of genistein for 6 days prior to irradiation. Example 6 administers a single dose of 200 mg/kg. Example 8 uses a dose level of 50 mg/kg to 200 mg/kg. Example 9 administers a dose of 20 mg/kg. The subject is a human. See column 4, lines 44-47. Elder et al. teach that genistein displays antitumor, antimetastatic, and antiangiogenic properties (suppression of blood-vessel growth). See column 10, lines 7-30. Elder et al. teach that genistein has been used in treating cystic fibrosis, wherein the symptoms include chronic obstructive lung disease. See column 11, lines 9-33. Chronic obstructive lung disease includes inflammation and scarring (fibrosis) as evidenced by the Cleveland Clinic.
Regarding instant claim 5, Example 8 comprises nanoparticulate genistein with a d(0.5) of 0.136 µm which is less than 0.3µm.
Regarding instant claims 7-8, the composition additionally comprises a diluent and preservative. See claim 2 and column 9, lines 46-59.
Regarding instant claim 9, the composition additionally comprises a nonionic surfactant. See claim 2.
Regarding instant claim 11, genistein is present in an amount ranging from 40 to 75%. See claim 8.
Regarding instant claim 12, genistein may be present at a concentration of 275 mg/ml to 325 mg/ml. See claim 1.
Regarding instant claim 13, the composition is formulated as a capsule for oral delivery. See column 9, lines 46-59.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to administer genistein once daily, 5-6 days prior to exposure of mixed field radiation, because Elder, Jr specifically exemplify administration at 6 days prior for Gy 60Co radiation but also teach the use against nuclear explosions. Since nuclear explosions are mixed field radiation, it would have been obvious to try a similar dosing time table of 6 days prior for mixed field radiation. It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to modify the dosing regimen, including amounts of genistein and frequency, to achieve the optimal desired effect because Elder, Jr teach various frequencies including one or twice daily and various effective amounts ranging from 20 to 200 mg/kg. Since Elder, Jr et al. teach administering genistein to humans prior to or after nuclear explosions, it would have been well within the purview of the skilled artisan to administer genistein to first responders or members of the military since they are humans likely to be called upon to help in a nuclear disaster. It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to administer genistein to a subject exposed to 32% neutron radiation and 68% gamma radiation because genistein is known to be effective against radiation, including nuclear radiation which includes both gamma and neutron radiation. One would have been motivated, with a reasonable expectation of success, to administer the genistein to reduce the deleterious effects of radiation exposure, including cardiovascular, tissue fibrosis, and inflammation, because Elder et al. teach the antiangiogenic properties of genistein and effective treatment of cystic fibrosis which includes inflammation and tissue fibrosis.
Response to Arguments
Applicants’ arguments filed 9 September 2025 have been fully considered but they are not persuasive.
7. Applicants argued, “There is no teaching in the cited references that genistein can be used prophylactically 5 to 6 days prior to potential radiation exposure to reduce, mitigate, or prevent development of cardiovascular diseases, tissue fibrosis, inflammation and neurodegenerative conditions caused by mixed field radiation. The etiology of the development of inflammation and tissue fibrosis in a patient having cystic fibrosis is different from the etiology of inflammation and tissue fibrosis caused by mixed field radiation.”
In response to applicants’ arguments, Elder et al. teach that genistein displays antitumor, antimetastatic, and antiangiogenic properties (suppression of blood-vessel growth). See column 10, lines 7-30. Elder et al. teach that genistein has been used in treating cystic fibrosis, wherein the symptoms include chronic obstructive lung disease. See column 11, lines 9-33. Chronic obstructive lung disease includes inflammation and scarring (fibrosis) as evidenced by the Cleveland Clinic. Elder specifically says that a subject at risk for or suffering from cystic fibrosis is identified and a therapeutically effective amount of genistein formulation selected from any of those described herein is administered to the subject. See column 11, lines 34-53. Thus Elder teach a prophylactic effect of genistein due to administering to a subject at risk, i.e., a subject not currently displaying symptoms. It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to administer genistein to a subject exposed to mixed field radiation because genistein is known to be effective against radiation, including nuclear radiation which includes both gamma and neutron radiation. One would have been motivated to administer the genistein to reduce the deleterious effects of radiation exposure, including cardiovascular, tissue fibrosis, and inflammation, because Elder et al. teach the antiangiogenic properties of genistein and effective use for treatment of cystic fibrosis which includes inflammation and tissue fibrosis. Even if the etiology of inflammation and tissue fibrosis is different, there would be a reasonable expectation of success because Elder is directed to administering the same composition, to the same patient population, with the same dosing requirements, wherein the patient population is subjected to the same type of radiation.
Thus this rejection is maintained.
Conclusion
8. Applicants’ 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.
Correspondence
9. No claims are allowed at this time.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA WORSHAM whose telephone number is (571)270-7434. The examiner can normally be reached Monday-Friday (8-5).
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/JESSICA WORSHAM/Primary Examiner, Art Unit 1615