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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1, 4, 6-7, 9, 12-14, 23-24, and 45, and the species bladder cancer, in the reply filed on 09/17/2025 is acknowledged. The traversal is on the ground(s) that amended claim 1 recites additional components that Jon does not teach (remarks, page 5). This is not found persuasive because Stephens (US 2014/0120076; Date of Publication: May 1, 2014 – cited in the IDS filed on 05/04/2023) teaches “Eosinophil peroxidase compositions and methods of their use for killing and/or inhibiting the growth of susceptible microorganisms are provided. The compositions include an eosinophil peroxidase, a peroxide or peroxide source, and amino acids glycine, L-alanine, and L-proline” (see, e.g., Stephens, abstract).
The requirement is still deemed proper and is therefore made FINAL.
Priority
The instant application filed on 05/04/2023 is a 371 of PCT/US2021/053155 filed on 10/01/2021, which claims priority to U.S. Provisional Application 63/112,447 filed on 11/11/2020. U.S. PRO 63/112,447 finds support for the instant invention; therefore, the effective filing date of the instant application is 11/11/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/16/2024, 10/13/2023, and 05/04/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawing Objections
The drawings are objected to because higher quality figures are required to Figures 1A and 1B. The Examiner is unable to read the x-axis and y-axis labels, as well as the figure legends.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 45 is objected to because of the following informalities: “Claim” should not be capitalized when reciting “Claim 14”. This is an objection, not a rejection, because it appears that this is a typological error. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b), Indefiniteness
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.
Claims 1, 4, 6-7, 9, 12-14, 23-24, and 45 are rejected under 35 U.S.C. 112(b) 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 1 recites “…eosinophil peroxidase, hydrogen peroxide or a peroxide- producing oxidase, amino acids L-alanine, L-proline, and glycine, and a bromide…”; however, it is unclear if the amino acids and the bromide are part of the claimed invention due to the use of the word “or” when listing the oxidases. For the purposes of applying prior art, the Examiner has interpreted this claim to be a pharmaceutical composition comprising eosinophil peroxidase; hydrogen peroxide or a peroxide- producing oxidase; amino acids L-alanine, L-proline, and glycine; and a bromide.
Claims 4, 6-7, 9, 12-14, 23-24, and 45 are included in this rejection because they depend on independent claim 1 and fail to rectify the noted deficiencies.
Claim Rejections - 35 USC § 103, Obviousness
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 1, 4, 6-7, 9, 14, 23-24, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Stephens (US 2014/0120076; Date of Publication: May 1, 2014 – cited in the IDS filed on 05/04/2023) in view of Bachelder (US 2019/0271703; Date of Publication: September 5, 2019).
Stephens’ general disclosure relates to “Eosinophil peroxidase compositions and methods of their use for killing and/or inhibiting the growth of susceptible microorganisms are provided. The compositions include an eosinophil peroxidase, a peroxide or peroxide source, and amino acids glycine, L-alanine, and L-proline” (see, e.g., Stephens, abstract). Moreover, Stephens discloses administering the composition to a surgical site, which can include a cancer surgical site (see, e.g., Stephens, [0019]).
Regarding claim 1 pertaining to the pharmaceutical composition, Stephens teaches administration of a composition comprising eosinophil peroxidase, a peroxide or peroxide source, and amino acids glycine, L-alanine, and L-proline (see, e.g., Stephens, abstract & [0010]-[0011]). Moreover, Stephens teaches that the composition also comprises bromide (see, e.g., Stephens, [0014]). Additionally, Stephens teaches, in Example 3, a formulation comprising eosinophil peroxidase, glucose oxidase, amino acids, and sodium bromide (see, e.g., Stephens, [0124]).
Regarding claim 4 pertaining to the eosinophil peroxidase catalyzing bromide oxidation, Stephens teaches “In the presence of peroxide and halide, the target bound eosinophil peroxidase catalyzes halide oxidation and facilitates the disproportionation of peroxide to singlet molecular oxygen (1O2) at the surface of the target microorganism, resulting in selective killing of the target microorganism with a minimum of collateral damage to the desired microorganism or physiological medium” (see, e.g., Stephens, [0002]). One of ordinary skill in the art would readily assume and understand that if a microorganism can be killed through this mechanism, that cancer cells would also be affected and/or killed. Moreover, the catalyzation of bromide oxidase and disproportionation of peroxide yielding singlet molecular oxygen is an inherent property of eosinophil peroxidase. Therefore, since the composition comprises eosinophil peroxidase, the inherent properties exhibited by eosinophil peroxidase would be present within the composition.
Regarding claims 6-7 pertaining to administration of a substrate and a peroxide-producing oxidase, Stephens teaches administration of glucose oxidase (i.e., peroxide-producing oxidase) and glucose (i.e., substrate) (see, e.g., Stephens, [0021]).
Regarding claim 9 pertaining to bromide, Stephens teaches that the bromide is sodium bromide (see, e.g., Stephens, [0014]).
Regarding claim 23 pertaining to the concentration of eosinophil peroxidase, Stephens teaches “about 0.1 to about 1,000 µg/ml of eosinophil peroxidase” (see, e.g., Stephens, [0015]). Additionally, Stephens teaches in Example 1 that the solution “may comprise from about 1 to 50,000 µg/ml of eosinophil peroxidase” (see, e.g., Stephens, [0084]), and proceeds to formulate a composition with 2.5 mg/ml (i.e., 2,500 µg/ml) of eosinophil peroxidase (see, e.g., Stephens, [0082]).
Regarding claim 24 pertaining to the peroxide-producing oxidase, Stephens teaches “the peroxide-producing oxidase is present in an amount effective to generate from 100 pmol to 50 µmol peroxide per ml per minute in the presence of a substrate for the oxidase” (see, e.g., Stephens, [0036]).
However, Stephens does not teach: treating solid cancer in a patient (claim 1); or wherein the solid cancer is bladder cancer (claims 14 and 45).
Bachelder’s general disclosure relates to “determining and diagnosing chemo-resistant tumor cell populations and methods of treatment” (see, e.g., Bachelder, [0003]). Moreover, Bachelder discloses chemotherapeutic agents, such as hydrogen peroxide, can be administered to chemo-resistant tumor cells within the present invention (see, e.g., Bachelder, [0068]-[0069], [0079]). Additionally, Bachelder teaches composition and methods for treating bladder cancer, wherein the cancer is a primary or metastatic tumor (see, e.g., Bachelder, [0060]).
Regarding claims 1, 14, and 45 pertaining to the treatment of solid cancer, Bachelder teaches that cancer to be treated through administration of hydrogen peroxide, is bladder cancer (see, e.g., Bachelder, [0060]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer Stephens pharmaceutical composition comprising an eosinophil peroxidase; a peroxide or peroxide source; amino acids glycine, L-alanine, and L-proline; and bromide, to treat bladder cancer, as taught by Bachelder. One would have been motivated to do so because Bachelder teaches that cancer, such as bladder cancer, can be a primary or metastatic tumor, and be chemotherapy resistant (see, e.g., Bachelder, [0060]). Additionally, Bachelder discloses chemotherapeutic agents, such as hydrogen peroxide, can be administered to treat chemo-resistant tumor cells within the present invention (see, e.g., Bachelder, [0068]-[0069], [0079]). Moreover, Stephens teaches administering the composition comprising an eosinophil peroxidase; a peroxide or peroxide source; amino acids glycine, L-alanine, and L-proline; and bromide to a surgical site, which can include a cancer surgical site (see, e.g., Stephens, [0019]). Additionally, Stephens teaches that the composition comprising an eosinophil peroxidase; a peroxide or peroxide source; amino acids glycine, L-alanine, and L-proline; and bromide is cytotoxic (see, e.g., Stephens, abstract & [0017]); therefore, one of ordinary skill in the art would expect for Stephens’ composition to exhibit cytotoxic properties against tumors, such as bladder cancer. Based on the teachings of Stephens and Bachelder, it would have been obvious to administer a composition comprising an eosinophil peroxidase; a peroxide or peroxide source; amino acids glycine, L-alanine, and L-proline; and bromide to treat bladder cancer. One would have expected success because Stephens and Bachelder both teach administration of compositions comprising hydrogen peroxide to cancer sites.
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Stephens and Bachelder as applied to claims 1, 4, 6-7, 9, 14, 23-24, and 45 above, and further in view of Kiel (U.S. Patent No. 4,486,408; Date of Publication: December 4, 1984 – cited in the IDS filed on 10/13/2023).
The teachings of Stephens and Bachelder, herein referred to as modified-Stephens-Bachelder, are discussed above as it pertains to treatment of a solid cancer with a composition comprising eosinophil peroxidase, a peroxide-producing oxidase, amino acids, and bromide.
However, modified-Stephens-Bachelder does not teach: wherein the solid cancer is a primary or metastatic tumor (claim 12); or wherein the pharmaceutical composition is administered extratumorally or intratumorally (claim 13).
Kiel’s general disclosure relates to “an enzymatic preparation for the control of tumor growth and immune diseases” (see, e.g., Kiel, pg. 2, col. 1, lines 12-13). Kiel discloses that “Ample evidence has shown that the combination of certain peroxidases with hydrogen peroxide and a halide ion produces a system with strong cytotoxic properties. The myeloperoxidase-hydrogen peroxide-chloride system forms a potent cytotoxic system effective against bacteria, fungi, viruses, mycoplasma, and various mammalian cells” (see, e.g., Kiel, pg. 2, col. 1, lines 15-18). Additionally, Kiel discloses “An equally cytotoxic system is obtained when instead of hydrogen peroxide, a hydrogen peroxide generating system is used. Thus, the glucose oxidase-horseradish peroxidase-chloride combination yields a potent cytotoxic system upon the addition of glucose” (see, e.g., Kiel, pg. 2, col. 1, lines 25-29). Moreover, Kiel discloses “several peroxidases, when used in combination with a hydrogen peroxide and/or superoxide generating system possess a potent cytotoxic activity toward prokaryotic and eukaryotic cells when administered to tumor-bearing animals” (see, e.g., Kiel, pg. 2, col. 2, lines 23-27), and that “this cytotoxic activity appears to be exclusively directed toward the neoplastic tissues” (see, e.g., Kiel, pg. 2, col. 2, lines 28-29).
Regarding claim 12 pertaining to the tumor, Kiel teaches primary and metastasized tumors are subject to the cytotoxic action of the immobilized enzymes (see, e.g., Kiel, pg. 2, col. 2, lines 56-58).
Regarding claim 13 pertaining to administration of the pharmaceutical composition, Kiel teaches “it is preferable that the material be injected into the tumor or proximal to the tumor” (see, e.g., Kiel, pg. 2, col. 2, lines 55-56).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer modified-Stephens-Bachelder’s pharmaceutical composition comprising an eosinophil peroxidase; a peroxide or peroxide source; amino acids glycine, L-alanine, and L-proline; and bromide, to a primary or metastasized tumor either intratumorally or extratumorally, as taught by Kiel. One would have been motivated to do so because Kiel teaches an enzymatic preparation for the control of tumor growth and immune diseases” (see, e.g., Kiel, pg. 2, col. 1, lines 12-13) and that “Ample evidence has shown that the combination of certain peroxidases with hydrogen peroxide and a halide ion produces a system with strong cytotoxic properties” (see, e.g., Kiel, pg. 2, col. 1, lines 15-18). Additionally, Kiel teaches “An equally cytotoxic system is obtained when instead of hydrogen peroxide, a hydrogen peroxide generating system is used. Thus, the glucose oxidase-horseradish peroxidase-chloride combination yields a potent cytotoxic system upon the addition of glucose” (see, e.g., Kiel, pg. 2, col. 1, lines 25-29). Furthermore, Kiel teaches “several peroxidases, when used in combination with a hydrogen peroxide and/or superoxide generating system possess a potent cytotoxic activity toward prokaryotic and eukaryotic cells when administered to tumor-bearing animals” (see, e.g., Kiel, pg. 2, col. 2, lines 23-27), and that “this cytotoxic activity appears to be exclusively directed toward the neoplastic tissues” (see, e.g., Kiel, pg. 2, col. 2, lines 28-29). Moreover, modified-Stephens-Bachelder teaches administration of a composition comprising eosinophil peroxidase, a peroxide or peroxide source, and amino acids glycine, L-alanine, and L-proline (see, e.g., Stephens, abstract & [0010]-[0011]). Moreover, modified-Stephens-Bachelder teaches that the composition also comprises bromide (see, e.g., Stephens, [0014]). Therefore, based on the teachings of modified-Stephens-Bachelder and Kiel, it would have been obvious to one of ordinary skill in the art to administer a composition comprising eosinophil peroxidase; a peroxide or peroxide source; amino acids glycine, L-alanine, and L-proline; and bromide to treat cancers. One would have expected success because modified-Stephens-Bachelder and Kiel both teach compositions comprising hydrogen peroxide and halide(s) for the treatment of diseases and/or infections.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9,782,459 in view of Kiel (U.S. Patent No. 4,486,408; Date of Publication: December 4, 1984 – cited in the IDS filed on 10/13/2023).
U.S. Patent No. 9,782,459, herein referred to as US’459, teaches a composition for killing or inhibiting the growth of non-sporular bacteria, comprising: (a) an eosinophil peroxidase; (b) glucose oxidase; and (c) amino acids glycine, L-alanine, and L-proline, wherein the amino acids enhance the antibacterial activity of the eosinophil peroxidase (see, e.g., US’459, claim 1); wherein the composition comprises bromide (see, e.g., US’459, claim 2); and wherein the composition comprises about 0.1 to about 1,000 μg/ml of eosinophil peroxidase (see, e.g., US’459, claim 3).
However, US’459 does not teach: the treatment of solid cancer.
Kiel’s general disclosure relates to “several peroxidases, when used in combination with a hydrogen peroxide and/or superoxide generating system possess a potent cytotoxic activity toward prokaryotic and eukaryotic cells when administered to tumor-bearing animals” (see, e.g., Kiel, pg. 2, col. 2, lines 23-27), and that “this cytotoxic activity appears to be exclusively directed toward the neoplastic tissues” (see, e.g., Kiel, pg. 2, col. 2, lines 28-29).
Therefore, based on the teachings of US’459 and Kiel, it would have been obvious to administer a composition comprising an eosinophil peroxidase, hydrogen peroxide, amino acids and bromide to a patient to treat cancer. Additionally, although US’459 claims 1-3 are composition claims, they can be used in a method to treat solid cancer in view of Kiel.
Claims 1, 6-7, 14, and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5-9 of copending Application No. 18/855,270 (reference application; herein referred to as App’270).
Although the claims at issue are not identical, they are not patentably distinct from each other because App’270 teaches a method of treating a solid cancer in a patient, the method comprising: administering an effective amount of a pharmaceutical composition comprising myeloperoxidase, hydrogen peroxide or a source of hydrogen peroxide, and halide to the patient (see, e.g., App’270, claim 1); wherein the source of hydrogen peroxide is a peroxide- producing oxidase that produces hydrogen peroxide in the presence of a substrate for the oxidase (see, e.g., App’270, claim 2); wherein the peroxide-producing oxidase is glucose oxidase and the substrate is glucose (see, e.g., App’270, claim 3); wherein the composition further comprises one or more amino acids (see, e.g., App’270, claim 5); wherein the one or more amino acids is selected from the group comprising glycine, L-alanine, D-alanine, L-alanine anhydride, L-glutamine, L- glutamic acid, glycine anhydride, hippuric acid, L-histidine, L-leucine, D-leucine, L- isoleucine, D-isoleucine, L-lysine, L-ornithine, D-phenylalanine, L-phenylalanine, L- proline, L-hydroxyproline, L-serine, L-taurine, L-threonine, D-threonine, L-tyrosine, L- valine, D-valine, beta amino acids, such as beta alanine, L-beta-homoleucine, D-beta- homoleucine, 3-aminobutanoic acid, L-2,3-diaminopropionic acid monohydrochloride, D- 2,3-diaminopropionic acid monohydrochloride, L-3-aminoisobutyric acid, D-3-amnoisobutyric acid, ethyl 3-aminobutyrate, sarcosine methyl ester hydrochloride and nipecotic acid, or an alkyl ester or pharmaceutically acceptable salt thereof (see, e.g., App’270, claim 6); wherein the amino acids are glycine and L-proline (see, e.g., App’270, claim 7); wherein the solid cancer is selected from the group comprising: breast cancer, lung and bronchus cancer, prostate cancer, colon and rectum cancer, melanoma of the skin, bladder cancer, cervical cancer, kidney and renal pelvis cancer, endometrial cancer, pancreatic cancer, thyroid cancer, liver cancer, brain cancer and spinal cord cancer (see, e.g., App’270, claim 8); and wherein the solid cancer is bladder cancer (see, e.g., App’270, claim 9).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 4, 6-7, 9, 12-14, 23-24, and 45 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653