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 .
Foreign Priority
The present application claims priority to the applications, FI20215608 and PCT/EP2022/0638811, with effective filing dates of 21 May 2021 and 20 May 2022, respectively.
Claim Status
This Office Action is in response to Applicant’s Amendment filed, 21 November 2023, wherein Applicant amended claims 1-2, 4-7, 10, 12-13, 15-22, and 25, canceled claims 3, 8-9, 11, 23-24, and 26-27, and added new claim 28.
Claims 1-2, 4-7, 10, 12-22, 25, and 28 are pending.
Information Disclosure Statement
The Information Disclosure Statement filed on 21 February 2024 and the references cited therein have been considered, unless indicated otherwise.
The reference, Harrison (Carsinogenesis, 1986, 7(11), 1903-1908) is lined through, because a copy was not provided. A copy of the abstract was provided, but the relevant pages as cited are pages 1903-1908, which were not provided. See MPEP § 609.01(B)(2)(b).
Specification
1. The following title is suggested: Compounds Inhibiting the Synergistic Carcinogenic Effect of Heavy Metals in the Presence of Other Carcinogens for Use in the Treatment of Cancer.
2. The attempt to incorporate subject matter into this application by reference to Mandel and Ryser (1984), Harrison and Heath (1986), US 10,463,695, and WO2020/159987 is ineffective because a list of references in the specification does not substitute an IDS.
Claim Interpretation
For clarity, the Examiner interprets the phase, “the synergistic carcinogenic effect,” in claims 1, 4-6, 16-18, and 20-21 to be any carcinogenicity conferred by a carcinogen.
For clarity, the Examiner interprets the phrase, “a compound inhibiting the synergistic carcinogenic effect of cadmium,” to be a metal chelator that has at least two functional groups which donate a pair of electrons to the metal, as evidenced by Millipore Sigma (“Chelators,” < https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/protein-biology/protein- purification/chelators?srsltid=AfmBOoo8GSZ4_XfB3PXg_G0Mc2_2JVW4NQQ1c7nOfqkTTiIBu9mMT70r>, accessed 19 Feb 2026).
Claim Objections
3. Claim 6 is objected to because of the following informalities: typographic errors relating to spelling of “carsinogenic.”
4. Claim 13 is objected to because of the following informalities: reciting the intended use in reference to “a subject,” when the claim upon which it depends refers to the intended use in “a patient” (claim 1). It is ambiguous if the two terms are interchangeable in view of the instant specification or if these terms differ.
5. Claim 25 is objected to because of the following informalities: typographic errors relating to the term, “AMES,” which claims 7 and 18 and Thresher (Regulatory Toxicology and Pharmacology, 2020, 116(104749), 1-5) refer to as “Ames.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
6. Claim 1, 13, and 15 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 inhibiting cadmium carcinogenesis and treating lung cancer, prostate cancer, kidney cancer, pancreatic cancer, breast cancer, urinary bladder cancer, large intestinal cancer, skin cancer, and leukemia via a metal chelator, does not reasonably provide enablement for a) preventing any and all cancer or b) treating any cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
The instant claims are directed to a method of treating or preventing a cancer via administration of a compound that inhibits cadmium carcinogenesis. Thus, encompassing all cancers and prevention thereof.
As such, the breadth of the claims is great.
Level of Skill in the Art
The level of skill in the art is a clinician or an artisan with a PhD.
State of the Prior Art
Huff (Int. J. Occup. Environ. health, 2007, 13(2), 1-19) teaches cadmium-induced cancers in animals and humans (abstract). Huff specifies that cadmium causes cancers in experimental animals at many sites and the carcinogenicity mechanism is multi-factorial (page 9, paragraph 4). Huff further details several different cancers caused by cadmium: lung cancer, prostate cancer, kidney cancer, pancreatic cancer, breast cancer, and urinary bladder cancer (pages 6-9).
Shu (Cancer Metastasis Rev, 2010, 29, 483-502) teaches carcinogenesis is a multi-step process and that cancer initiation, promotion, and progression involve a series of epigenetic and genetic alteration affecting oncogenes and tumor suppressor genes (page 483, column 2, paragraph 2). Shu further describes that inhibition of each stage of carcinogenesis is possible (page 483, column 2, paragraph 2). Shu details that current carcinogenicity suppression efforts are known for inhibiting carcinogenesis in the following categories: (1) cell cycle and apoptosis regulation (2) anti-oxidative stress and anti-inflammatory activities; (3) drug resistance of cancer cells; and (4) specific molecular targets targeting carcinogenesis and metastasis (page 495, column 1, paragraph 3). However, Shu teaches that carcinogenicity suppression has not been expanded to prevention: (1) prevention of cancer initiation through DNA repair, detoxification, free-radical scavenging, and carcinogen metabolism and (2) prevention of tumor promotion and progression through inhibition of proliferation and angiogenesis, induction of apoptosis, and differentiation and reduction of inflammation and increased immunity (page 483, column 2, paragraph 2).
Ohanian (WO 2020/159987, published 6 Aug 2020, see IDS filed 21 Feb 2024) teaches methods of treating leukemia via metal chelators and combination therapies in patients (abstract). Ohanian describes several metals to be chelated, and in particular, cadmium ([0051]). Further, Ohanian describes metal chelators are chosen from EDTA, dimercaptosuccinic acid (DMSA), 2,3- dimercapto-l-propanesulfonic acid (DMPS), BAL, N-acetylcysteine (NAC), deferasirox, deferiprone, deferoxamine, pentetate calcium trisodium (Ca-DPTA), pentetate zinc trisodium (Zn-DTPA), trientine, tetrathiomolybdate, and dexrazoxane ([0038]).
Vucenik (J Nutr Sci Vitaminol, 2019, 65, S18-S22, see IDS filed 21 Feb 2024) teaches the anticancer properties of inositol hexaphosphate and inositol (abstract). Further Vucenik teaches that inositol hexaphosphate is also referred to as IP6, myo-inositol hexaphosphate, InsP6, or phytic acid (page S18, column 1, paragraph 2). Vucenik additionally teaches that phytic acid blocks activation of various carcinogens, stimulates detoxification, enhances the immune system, and suppresses proliferation (page S19, column 2, paragraph 1). Vucenik teaches that phytic acid has therapeutic activity against prostate cancer, large intestinal cancer, lung cancer, skin cancer, and breast cancer (page S19, column 2, paragraph 2; page S20, column 1, paragraphs 1-2). Vucenik mentions that preventative and therapeutic potential of phytic acid; however, Vucenik details that anecdotal evidence and in vitro studies fuel the idea that phytic acid can prevent cancer (page S19, column 2, paragraphs 1-2; page S20, column 1, paragraph 1; page S20, column 2, paragraph 3). Farther down the drug development pipeline, Leenaars (J Transl Med, 2019, 17(223), 1-22) teaches that current drug development is handicapped by high attrition rates and that many molecules that were promising during preclinical development fail during subsequent clinical testing (page 1, column 1, paragraph 1). Leenaars further teaches that animals and humans are complex systems and therefore always unpredictable (page 2, column 1, paragraph 1), which further underscores the unpredictability of the art and translation of promising candidate from in vitro models to in vivo models and beyond into humans. Thus, while Vucenik suggests potential of phytic acid to prevent cancer, Leenaars teaches that potential is not guaranteed to translate into other models.
Thus, while the prior art teaches inhibiting cadmium carcinogenesis and treating cancer in lung cancer, prostate cancer, kidney cancer, pancreatic cancer, breast cancer, urinary bladder cancer, and leukemia, these methods are taught for the treatment of specific cancers. The prior art is silent regarding preventing any and all cancer and treating all cancers.
Predictability in the Art
Huff teaches that the identification of chemicals first identified as being carcinogenic in bioassays is controversial as the findings are debated in regard to relevance and validation to predict human cancer risks (page 11, paragraph 1). However, Huff specifies that cadmium and cadmium compounds are causally associated with cancer, mainly of the lung (page 12, paragraph 2).
Ohanian teaches that stratifying patients by risk according to imbalance in essential and toxic metals, patient outcomes can be predicted, such as survival likelihood at a given date ([00414]). Ohanian describes several metals to be chelated, and in particular, cadmium ([0051]). Ohanian describes metal chelators are chosen from EDTA, dimercaptosuccinic acid (DMSA), 2,3- dimercapto-l-propanesulfonic acid (DMPS), BAL, N-acetylcysteine (NAC), deferasirox, deferiprone, deferoxamine, pentetate calcium trisodium (Ca-DPTA), pentetate zinc trisodium (Zn-DTPA), trientine, tetrathiomolybdate, and dexrazoxane ([0038]).
Vucenik (J Nutr Sci Vitaminol, 2019, 65, S18-S22, see IDS filed 21 Feb 2024) teaches the anticancer properties of inositol hexaphosphate and inositol (abstract). Further Vucenik teaches that inositol hexaphosphate is also referred to as IP6, myo-inositol hexaphosphate, InsP6, or phytic acid (page S18, column 1, paragraph 2).
Diaz-Uriarte (PLOS Computational Biology, 2019, 15(8): e1007246, 1-29) teaches that improving the ability to predict paths of tumor progression is helpful for diagnostic, prognostic, and treatment purposes (page 2, paragraph 2). Diaz-Uriarte describes that direct information about paths of tumor progression is scare, but cancer progression models can be used to predict the tumor progression path and use cross-sectional data as input (abstract). Diaz-Uriarte teaches that the best performing cancer progression model was unreliable when applied to twenty-two cancer data sets and that feature selection can have a detrimental selection on the performance of the model, thus highlighting the unpredictability of the art (abstract; page 22, paragraph 2).
Leenaars (J. Transl. Med., 2019, 17(223), 1-22) teaches that current drug development is handicapped by high attrition rates and that many molecules that were promising during preclinical development fail during subsequent clinical testing (page 1, column 1, paragraph 1). Leenaars further teaches that animals and humans are complex systems and therefore always unpredictable (page 2, column 1, paragraph 1), which further underscores the unpredictability of the art and translation of promising chemical candidate from in vitro models to in vivo models and beyond into humans.
Thus, Huff, Ohanian, and Vucenik teach treating lung cancer, prostate cancer, kidney cancer, pancreatic cancer, breast cancer, urinary bladder cancer, large intestinal cancer, skin cancer, and leukemia via metal chelator is predictable, but Diaz-Uriarte and Leenaars teach that treating all cancer is unpredictable, much less preventing cancer.
Working Examples
The instant specification teaches screening of three anticarcinogenic compounds in Salmonella typhimurium TA1535 (standard Ames tester strain; page 8, lines 24-31). The instant specification does not teach applying the anticarcinogenic compounds to any cancer cell lines for in vitro testing, much less in vivo or in patient testing.
Thus, it is not possible to determine all the types of cancer that the anticarcinogenic compounds can treat, much less prevent.
Quantity of Experimentation
The amount of experimentation required to determine which compound, which cancer, in what amounts, what order, would be astronomical. A skilled artisan would be required to start with proof-of-concept and proceed through all levels of lead identification and optimization, which is invention and not development; this is undue amount of experimentation.
As such, while the specification is enabling for treating inhibiting cadmium carcinogenesis and treating cancer in lung cancer, prostate cancer, kidney cancer, pancreatic cancer, breast cancer, urinary bladder cancer, large intestinal cancer, skin cancer, and leukemia via a metal chelator, it does not reasonably provide enablement for a) preventing any and all cancer or b) treating any cancer.
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.
7. Claims 13-15 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 13 recites a method of preventing or treating cancer in a subject, comprising administering to a subject the composition according to claim 1. Claim 1 recites a composition comprising a compound for the prevention or treatment of cancer in a patient or the prevention of the recurrence of cancer in a patient. The terms “subject” and “patient” are not defined by the claim or the specification. It is also unclear whether these terms in light of the specification are synonyms or have different meanings. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention, because the terms are ambiguous as to if they are interchangeable. Thus, claim 13 is indefinite.
Similarly, claim 14 depends upon claim 13 and specifies that zinc is further administered to the subject. However, the ambiguity regarding the terms “subject” and “patient” does not allow one of ordinary skill in the art to be reasonably apprised of the scope of the invention. Thus, claim 14 is indefinite.
Similarly, claim 15 depends upon claim 13 and specifies that the subject is being simultaneously treated for cancer by another therapy, said patient has been treated for cancer, and/or said patient has recovered from cancer. However, the ambiguity regarding the terms “subject” and “patient” does not allow one of ordinary skill in the art to be reasonably apprised of the scope of the invention. Thus, claim 15 is indefinite.
Claim Rejections - 35 USC § 102
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 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.
8. Claims 1-2, 6-7, 12-15, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ohanian (WO2020/159987, published 6 Aug 2020, see IDS filed 21 Feb 2024) as evidenced by Rahimzadeh (Caspian J Intern Med, 2017,8(3), 135-145), Wikipedia 1 (“Heavy Metals,” Wikipedia, 2020, < https://web.archive.org/web/20200606013514/https://en.wikipedia.org/wiki/Heavy_metals>, accessed 13 Feb 2026), and Wikipedia 2 (“Ethylenediaminetetraacetic acid,” Wikipedia, 2020, < https://web.archive.org/web/20200222231610/https://en.wikipedia.org/wiki/Ethylenediaminetetraacetic_acid>, accessed 13 Feb 2026).
Ohanian teaches treating cancer via combination therapy with anticancer agents and metal chelators ([0004]). Ohanian specifically teaches a method of treating leukemia in patients via a composition of EDTA and daily oral antioxidants, vitamins, and minerals, such as zinc ([00446-00474]).
Regarding claim 1, Ohanian teaches a composition of zinc and EDTA ([00446]; [00450]), which is a cadmium chelator, as evidenced by Rahimzadeh (page 140, column 1, paragraph 1). Ohanian further teaches administration of the zinc/EDTA composition for treating leukemia in a patient in the presence of another carcinogen, lead and arsenic ([00410]; [00452]).
Regarding claim 2, Ohanian teaches a composition of zinc as the salt, zinc gluconate ([00450]).
Regarding claim 6, Ohanian teaches a composition that is an inhibitor of cadmium, wherein the level of mutagenesis in the cells is lower in the presence of the composition as shown in the p53 mutation becoming undetectable ([00470]). Additionally, claim 6 is a product-by-process claim, and as such, the patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). See MPEP § 2113(I). Thus, Ohanian teaches a composition wherein the compound inhibiting the carcinogenic effect of cadmium is obtained by a cell-based screening system for detection of mutagens and contacting a candidate compound with the screening system in the presence of cadmium and at least one other carcinogen and said candidate compound is an inhibitor of cadmium if the level of mutagenesis in the cells is lower in the presence of said candidate compound than in the absence of said compound ([00470]).
Regarding claim 7, although claim 7 narrows the process of claim 6, there is no evidence of record that the limitations of claim 7 would alter the structure of claim 6. See MPEP § 2113(I). Thus, Ohanian teaches a composition wherein the cell-based screening system for detection of mutagenes is an Ames test ([00470]).
Regarding claim 12, Ohanian teaches a pharmaceutical composition ([00446]; [00450]).
Regarding claim 13, Ohanian teaches a method of treating leukemia in a patient via administering a composition of EDTA and zinc ([00442]-[00474]).
Regarding claim 14, Ohanian teaches a method of treating leukemia in a patient via administering a composition of EDTA and zinc ([00446]; [00450]).
Regarding claim 15, Ohanian teaches that a patient is simultaneously undergoing AML and MDS therapy ([00443]).
Regarding claim 20, Ohanian teaches administering a heavy metal chelating compound, such as EDTA ([00446]), as evidenced by Wikipedia 1 (page 5; page 67, paragraph 1) and Wikipedia 2 (page 1, paragraph 2).
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.
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.
Claims 4 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Ohanian (WO2020/159987, published 6 Aug 2020, see IDS filed 21 Feb 2024) as evidenced by Rahimzadeh (Caspian J Intern Med, 2017,8(3), 135-145), Wikipedia 1 (“Heavy Metals,” Wikipedia, 2020, < https://web.archive.org/web/20200606013514/https://en.wikipedia.org/wiki/Heavy_metals>, accessed 13 Feb 2026), and Wikipedia 2 (“Ethylenediaminetetraacetic acid,” Wikipedia, 2020, < https://web.archive.org/web/20200222231610/https://en.wikipedia.org/wiki/Ethylenediaminetetraacetic_acid>, accessed 13 Feb 2026).
Ohanian (WO2020/159987, published 6 Aug 2020, see IDS filed 21 Feb 2024) as evidenced by Rahimzadeh (Caspian J Intern Med, 2017,8(3), 135-145), Wikipedia 1 (“Heavy Metals,” Wikipedia, 2020, < https://web.archive.org/web/20200606013514/https://en.wikipedia.org/wiki/Heavy_metals>, accessed 13 Feb 2026), and Wikipedia 2 (“Ethylenediaminetetraacetic acid,” Wikipedia, 2020, < https://web.archive.org/web/20200222231610/https://en.wikipedia.org/wiki/Ethylenediaminetetraacetic_acid>, accessed 13 Feb 2026) is applied as discussed in the 35 U.S.C. 102 rejection above.
The Examiner notes the relevant teachings with respect to claims 1-2, 6-7, 12-15, and 20 set forth above and are incorporated herein by reference.
Additional relevant teachings are set forth below.
Ohanian teaches treating leukemia via combination therapy with anticancer agents and metal chelators ([0004]). Ohanian specifically teaches a method of treating leukemia in patients via a composition of EDTA and daily oral antioxidants, vitamins, and minerals, such as zinc ([00446-00474]).
Regarding claim 4, Ohanian fails to teach administration of DMPS to a patient in one embodiment ([00446-00474]).
However, Ohanian teaches the possibility of administration of DMPS to a patient for inhibiting the carcinogenic effect of cadmium ([00110]; [00262]). Ohanian specifically teaches metal chelators are chosen from EDTA, dimercaptosuccinic acid (DMSA), 2,3- dimercapto-l-propanesulfonic acid (DMPS), BAL, N-acetylcysteine (NAC), deferasirox, deferiprone, deferoxamine, pentetate calcium trisodium (Ca-DPTA), pentetate zinc trisodium (Zn-DTPA), trientine, tetrathiomolybdate, and dexrazoxane ([0038]).
It would have been prima facie obvious to one or ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to select the method of administering EDTA and EDTA composition of Ohanian ([00446-00474]) with the list of compounds competent in method of treating of Ohanian ([00110]; [00262]) to develop a method of treating leukemia in patients to arrive at instant claim 4. One of ordinary skill would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Ohanian teaches treating leukemia via combination therapy with anticancer agents and metal chelators,
-Ohanian teaches a method of treating leukemia in patients via a composition of EDTA and daily oral antioxidants, vitamins, and minerals, such as zinc,
-Ohanian teaches a composition of zinc and EDTA, which is a cadmium chelator,
-Ohanian teaches administration of the zinc/EDTA composition for treating leukemia in a patient in the presence of another carcinogen, lead and arsenic,
-Ohanian teaches possibility of administration of DMPS to a patient for inhibiting the carcinogenic effect of cadmium,
-Ohanian teaches metal chelators are chosen from EDTA, dimercaptosuccinic acid (DMSA), 2,3- dimercapto-l-propanesulfonic acid (DMPS), BAL, N-acetylcysteine (NAC), deferasirox, deferiprone, deferoxamine, pentetate calcium trisodium (Ca-DPTA), pentetate zinc trisodium (Zn-DTPA), trientine, tetrathiomolybdate, and dexrazoxane,
-Ohanian teaches lower dosages of chemotherapeutic may be administered to the subject as a result of combination therapy (abstract),
-Ohanian teaches that there are currently no standard treatment protocols for broad-spectrum metal detoxification or metal rebalancing for cancer, cancer maintenance therapy, cancer prevention, or for treatment or prevention of acute or chronic diseases and that cancer continues to be a significant clinical problem ([0003]), and
-Ohanian teaches that combination therapies that include metal chelators may be particularly beneficial for treatment of various cancers, such as leukemia ([0004]).
As such, an artisan having ordinary skill in the art would have been motivated to make such a selection, to predictably arrive at a composition or method of treating leukemia via administration of DMPS.
Regarding claim 16, Ohanian teaches administration of DMPS ([00110]; [00262]).
10. Claims 5, 10, 17, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Ohanian (WO2020/159987, published 6 Aug 2020, see IDS filed 21 Feb 2024) as evidenced by Rahimzadeh (Caspian J Intern Med, 2017,8(3), 135-145), Wikipedia 1 (“Heavy Metals,” Wikipedia, 2020, < https://web.archive.org/web/20200606013514/https://en.wikipedia.org/wiki/Heavy_metals>, accessed 13 Feb 2026), and Wikipedia 2 (“Ethylenediaminetetraacetic acid,” Wikipedia, 2020, < https://web.archive.org/web/20200222231610/https://en.wikipedia.org/wiki/Ethylenediaminetetraacetic_acid>, accessed 13 Feb 2026) in view of Vucenik (J. Nutr. Sci. Vitaminol., 2019, 65, S18-S22, see IDS filed 21 Feb 2024).
Ohanian (WO2020/159987, published 6 Aug 2020, see IDS filed 21 Feb 2024) as evidenced by Rahimzadeh (Caspian J. Intern. Med., 2017,8(3), 135-145), Wikipedia 1 (“Heavy Metals,” Wikipedia, 2020, < https://web.archive.org/web/20200606013514/https://en.wikipedia.org/wiki/Heavy_metals>, accessed 13 Feb 2026), and Wikipedia 2 (“Ethylenediaminetetraacetic acid,” Wikipedia, 2020, < https://web.archive.org/web/20200222231610/https://en.wikipedia.org/wiki/Ethylenediaminetetraacetic_acid>, accessed 13 Feb 2026) is applied as discussed in the 35 U.S.C. 103 rejection above.
Regarding claim 5, while Ohanian teaches compositions and method of treating leukemia in a patient via administering EDTA, dimercaptosuccinic acid (DMSA), 2,3- dimercapto-l-propanesulfonic acid (DMPS), BAL, N-acetylcysteine (NAC), deferasirox, deferiprone, deferoxamine, pentetate calcium trisodium (Ca-DPTA), pentetate zinc trisodium (Zn-DTPA), trientine, tetrathiomolybdate, and dexrazoxane, Ohanian differs from that of the instantly claimed invention in that Ohanian does not explicitly teach a method of treating prostate cancer, large intestinal cancer, lung cancer, skin cancer, and breast cancer via phytic acid.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to exemplify the composition and method of Ohanian with the method of administering phytic acid to treat prostate cancer, large intestinal cancer, lung cancer, skin cancer, or breast cancer via phytic acid as taught by Vucenik to arrive at the instantly claimed invention.
One of ordinary skill in the art would have been motivated to combine the composition and methods of Ohanian with the method of Vucenik to treat prostate cancer, large intestinal cancer, lung cancer, skin cancer, or breast cancer via phytic acid with a reasonable expectation of success, because Vucenik teaches that the use of non-toxic, naturally occurring compound is a good strategy for the management of cancer (page S18, column 1, paragraph 2; page S19, column 2, paragraph 2; page S20, column 1, paragraphs 1-2). Additionally, Vucenik teaches that intake of fiber with high concentrations of phytic acid show negative correlation with colon cancer (page S18, column 1, paragraph 1). Further, Vucenik teaches that the therapeutic nature of phytic acid is tied to its ability to block activation of various carcinogens, stimulation of detoxification, enhancement of the immune system, and suppression of proliferation (page S19, column 2, paragraph 1). Thus, one of ordinary skill in the art would have substituted one known element for another, and the results would be predictable.
As such, an artisan having ordinary skill in the art would have been motivated to make such a selection, to predictably arrive at instant claim 5: the compound is phytic acid.
Regarding claim 10, Ohanian teaches a composition comprising of DMPS and an anticancer reagent (mylotarg, cladribine, idarubicin, cytarabine, rituximab, ofatumumab, or blinatumomab, inotuzumab, gemtuzumab ozogamicin, ipilumumab, nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab; [0078]; [0082]; [0083]; [00420]). Vucenik teaches a composition comprising phytic acid. Because Vucenik teaches that phytic acid has therapeutic anticancer activity and Ohanian teaches the combination of chemotherapeutics with metal chelators, a person of ordinary skill in the art would reasonably substitute the chemotherapeutic of Ohanian with that of Vucenik. Thus, the combination of Ohanian and Vucenik teaches a composition comprising DMPS and phytic acid.
Regarding claim 17, Vucenik teaches the compound is phytic acid (page S18, column 1, paragraph 2; page S19, column 2, paragraph 2; page S20, column 1, paragraphs 1-2).
Regarding claim 28, Ohanian teaches a method of administering the combination of DMPS and an anticancer reagent (mylotarg, cladribine, idarubicin, cytarabine, rituximab, ofatumumab, or blinatumomab, inotuzumab, gemtuzumab ozogamicin, ipilumumab, nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab; [0078]; [0082]; [0083]; [00420]). Vucenik teaches a method of administering a composition comprising phytic acid. Because Vucenik teaches that phytic acid has therapeutic anticancer activity and Ohanian teaches the combination of chemotherapeutics with metal chelators, a person of ordinary skill in the art would reasonably substitute the chemotherapeutic of Ohanian with that of Vucenik. Thus, the combination of Ohanian and Vucenik teaches a method of administering DMPS and phytic acid simultaneously or sequentially in any order.
11. Claims 18-19, 21-22, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Ohanian (WO2020/159987, published 6 Aug 2020, see IDS filed 21 Feb 2024) as evidenced by Rahimzadeh (Caspian J. Intern. Med., 2017,8(3), 135-145), Wikipedia 1 (“Heavy Metals,” Wikipedia, 2020, < https://web.archive.org/web/20200606013514/https://en.wikipedia.org/wiki/Heavy_metals>, accessed 13 Feb 2026), and Wikipedia 2 (“Ethylenediaminetetraacetic acid,” Wikipedia, 2020, < https://web.archive.org/web/20200222231610/https://en.wikipedia.org/wiki/Ethylenediaminetetraacetic_acid>, accessed 13 Feb 2026) in view of Thresher (Regulatory Toxicology and Pharmacology, 2020, 116(104749), 1-5).
Ohanian (WO2020/159987, published 6 Aug 2020, see IDS filed 21 Feb 2024) as evidenced by Rahimzadeh (Caspian J Intern Med, 2017,8(3), 135-145), Wikipedia 1 (“Heavy Metals,” Wikipedia, 2020, < https://web.archive.org/web/20200606013514/https://en.wikipedia.org/wiki/Heavy_metals>, accessed 13 Feb 2026), and Wikipedia 2 (“Ethylenediaminetetraacetic acid,” Wikipedia, 2020, < https://web.archive.org/web/20200222231610/https://en.wikipedia.org/wiki/Ethylenediaminetetraacetic_acid>, accessed 13 Feb 2026) is applied as discussed in the 35 U.S.C. 103 rejection above.
Regarding claim 18, while Ohanian teaches compositions and a method of treating leukemia in a patient via administering EDTA, Ohanian differs from that of the instantly claimed invention in that Ohanian does not explicitly teach a method of treating cancer via obtaining a compound via a cell-based screening system for detection of mutagens, wherein if the level of mutagenesis in the cells is lower in the presence of compound than in the absence of compound.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to exemplify the composition and method of Ohanian with the method of screening for carcinogens via Ames test as taught by Thresher to arrive at the instantly claimed invention.
One of ordinary skill in the art would have been motivated to combine the composition and methods of Ohanian with the method of Thresher to treat leukemia with a reasonable expectation of success, because Thresher teaches a method of determining carcinogenicity in vitro in the presence of small molecules (abstract). Thresher additionally teaches that mutagenic impurities are compounds that react directly with DNA and potentially induce genetic mutations, which can initiate tumor formation (page 1, column 1, paragraph 1). Further, Thresher teaches that control of potentially mutagenic impurities in pharmaceutical products is of key importance in assessing carcinogenic risk to humans and that recent discovery of nitrosamine impurities in several marketed pharmaceuticals has increased interest in mutagenic and carcinogenic potential (abstract). Thresher additionally teaches that investigation of mutagenicity via bacterial reverse mutation assay (Ames test), which is commonly used as an in vitro predictor of the in vivo carcinogenic potential (page 2, column 1, paragraph 2). Thus, one of ordinary skill in the art would have substituted one known element for another, and the results would be predictable.
As such, an artisan having ordinary skill in the art would have been motivated to make such a selection, to predictably arrive at instant claim 18: the compound inhibiting cadmium is obtained via a cell-based screening system for detection of mutagens, wherein if the level of mutagenesis in the cells is lower in the presence of compound than in the absence of compound.
Regarding claim 19, Thresher teaches that the cell-based screening system for detection of mutagenes is an Ames test (page 2, column 1, paragraph 2).
Regarding claim 21, Ohanian teaches a method of treating leukemia in patients (who having living cells) with said cells in the presence of cadmium, a different carcinogen, and an anticarcinogen and then detecting which anticarcinogens decrease the carcinogenic effect ([00446-00474]). Thresher teaches a method of detecting carcinogenicity of a compound in a cell culture via Ames test (abstract; page 2, column 1, paragraph 2). Because Ohanian teaches detecting anticarcinogenic activity of metal chelators in patients having leukemia and Thresher teaches using the Ames test to predict carcinogenic potential, a person of skill in the art would reasonably utilize the Ames test to detect anticarcinogenic compounds in vitro. Thus, the combination of Ohanian and Thresher teaches utilizing the Ames test to detect anticarcinogenic compounds in the presence of cadmium and another carcinogen in vitro.
Regarding claim 22, Thresher teaches the carcinogen is nitrosamine (abstract; page 2, column 1, paragraph 2).
Regarding claim 25, Thresher teaches the method is an Ames test (abstract; page 2, column 1, paragraph 2).
Conclusion
No claim is allowed.
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/MADELINE M. DEKARSKE/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622