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 .
Claim Rejections - 35 USC § 112
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 32, 156 and 161 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 156 recites the broad recitation 30mg to 1400mg, and the claim also recites 200mg to 550mg, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 18 recites the limitation "the cardiac disease" in lines 3-3. There is insufficient antecedent basis for this limitation in the claim. Claim 8 from which 18 depends does noy recite “a cardiac disease”.
Claim 32 recites “A method of treating cardiovascular disease comprising administering therapeutically effective amount of compound 1, to achieve at least one of:…” the claim proceeds to recite pharmacokinetic parameters of compound 1. It is unclear if the recitation of the pharmacokinetic parameters carries patentable weight. The claim recites an intent to achieve said parameters, but does not limit the outcome of the method to said parameters. Furthermore, the amount administered is a therapeutically effective amount. In order to advance examination Examiner will interpret administration of a therapeutically effective amount of compound 1 to be sufficient to achieve the recited pharmacokinetic parameters.
Claim 161 recites “wherein the therapeutically effective amount is 150mg, 300mg, 450mg per day”. The amounts are not recited as alternative embodiments. It is unclear if all three amounts must be administered or one of the three amounts can be administered.
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.
Claim(s) 8, 13, 32, 33, 34, 35, 130, 131, 136, 138, 139 and 147 is/are rejected under 35 U.S.C. 102(a)(1) and under 35 U.S.C. 102(a)(2) as being anticipated by Khan (US 2019/0337903).
The rejected claims comprise 4 independent claims (8, 32, 130 and 147) which are addressed separately.
Claims are directed to administration of 5-[(2,4-dinitrophenoxy)methyl]-1-methyl-2-nitro-1H-imidazole, which from here on will be referred to as compound 1.
Claims 8, 13, 33, 34 and 35:
Interpretation of subject population in claim 8
Claims 8 is directed to a method for treating heart failure with ejection fraction being preserved, reduced, or mid-range. The listed ejection fractions encompass all possible ejection fractions in a subject with heart failure. Any subject with heart failure is therefore within the scope of the claimed subject population.
Khan discloses the currently clamed compound (from here on compound 1) in paragraph [0089] and describes utility of the compound as a medicament for treating mitochondria-related disorders including heart failure (paragraph [0090]). In claim 2, Khan discloses a method of treating mitochondria-related disorder by administering effective amount of compound 1 to a subject. Khan meets all of the limitations of current claim 8.
Claim 13 is directed to physiological effect which is a result of administration of compound 1. Since Khan discloses treatment of heart failure by administering effective amount of compound 1, it is inherent that in the method of Khan the subject will experience a reduction in risk of death.
Claims 33, 34 and 35 are directed method not causing clinically significant risk of adverse events following administration. Since Khan discloses administration of the claimed compound (compound 1) to the claimed subject population (heart failure subjects) at the claimed dose (therapeutically effective dose) it is inherent that the practice of Khan’s method will not cause significant risk of adverse events after administration. This includes the specific adverse events recited in claims 34 and 35.
Claim 32:
In claim 7 (page 21) Khan discloses a method of treating cardiovascular disease in a subject in need thereof comprising administering a therapeutically effective amount of compound 1. Khan does not disclose the pharmacokinetic parameters that result from administration of therapeutically effective amount of compound 1. However, since Khan discloses administration of the currently claimed agent, to the claimed subject population, at claimed dose, the resulting pharmacokinetic parameters are inherently the same as currently claimed.
Claims 130, 131, 136, 138, 139:
Claim interpretation
Claim 130 is directed to a method of reducing liver fat by at least 50% or lipids by at least 10% in a subject by administering therapeutically effective amount of compound 1. Claim 130 does not identify a subject population, but dependent claims limit subjects to specific disorders including NAFDL and NASH (claims 131 and 136). Limitations of claim 130 are considered to met by administration of a therapeutically effective dose of compound 1 to a subject with NASH or NAFDL.
Claims 130, 131, 136, 138 and 139 are directed reducing liver fat by at least 50% or lipids by at least 10% in a subject with NASH or NAFDL by administering therapeutically effective amount of compound 1. Khan discloses a method of treating NAFDL or NASH in a subject in need by administering to said subject a therapeutically effective amount of compound 1 (page 21, claims 2 and 4). Since Kahn discloses administration of the currently claimed active agent (compound 1) to the claimed subject population (subjects with NASH or NAFDL) as the currently claimed dose (therapeutically effective amount), it is inherent that the subjects will benefit from reduction of liver fat by at least 50% or of lipids by at least 10%. For the same reasons the limitation of claim 138 directed to reduction of body weight by at least 10% and of claim 139 directed to method not causing a clinically significant adverse effect, are inherently met by disclosure of Kahn.
Claim 147:
Claim interpretation
Claim 147 is directed to a method of reducing risk of cancer in a subject comprising administering compound 1. The term “subject” is interpreted to include subjects who do not currently have cancer. Since the only active method step is administration of compound 1, any subject to whom compound 1 is administered is within the scope of the claim
Khan discloses a method of treating NASH in a subject by administering to a subject compound 1 (page 21 claims 2 and 4). The subject to whom compound 1 is administered inherently benefits from reduced risk of cancer. Inherency is based on administration of the claimed agent (compound 1) to claimed subject population (subject).
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) 8 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Khan et al as applied to claim 8 above, and further in view of Editorial (The European Journal of Heart Failure, 2005, 7, 699-703).
Ascertaining the difference
Khan teaches treatment of heart failure by administration of compound 1, but does not limit the subject population to subjects experiencing the symptoms of heart failure recited in claim 9.
Secondary reference
Editorial teaches breathlessness and fatigue as classical symptoms of heart failure (page 700, column 1, first paragraph).
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application, would have found it obvious to treat heart failure in a subject who is experiencing common symptoms of heart failure. It would have been obvious to administer compound 1 to a subject with heart failure who is exhibiting fatigue and/or breathlessness, which are common symptoms.
Claim(s) 8 and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Khan et al as applied to claim 8 above, and further in view of Bensimhon et al (The American Journal of cardiology, 2008, 15, 712-717)
Ascertaining the difference
Khan teaches treatment of heart failure by administration of compound 1, but does teach assessing peak oxygen consumption as a measure of treatments’ efficacy.
Secondary reference
Bensimhon teaches that change in peak oxygen consummation is often used to assess the effectiveness of an intervention (Abstract).
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application, would have found it obvious to assess the effectiveness of treatment of heart failure by administration of compound 1. Bensimhon teaches that measurement of a change in oxygen consumption is a common method to assess efficacy of treatment. One would have found it obvious to measure oxygen consumption before and after treatment with compound 1 in order to assess the efficacy of intervention.
Claim(s) 8 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Khan et al as applied to claim 8 above, and further in view of Passantino et al (Journal of the American College of Cardiology, 2006, 48(1), 99-105)
Ascertaining the difference
Khan teaches treatment of heart failure by administration of compound 1, but does teach assessing 6MWD.
Secondary reference
Passantino teaches that change in 6MWD is a measure of response to therapeutic intervention (page 99, column 1, paragraph 1).
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application, would have found it obvious to assess the effectiveness of treatment of heart failure by administration of compound 1. Passantino teaches that measurement of a change 6MWD is a common method to assess efficacy of treatment. One would have found it obvious to measure 6MWD before and after treatment with compound 1 in order to assess the efficacy of intervention.
Claim(s) 8, 18, is/are rejected under 35 U.S.C. 103 as being unpatentable over Khan et al as applied to claim 8 above, and further in view of Caraballo et al (Journal of the American Heart association, 2019, 8(23))
Ascertaining the difference
Khan teaches treatment of heart failure by administration of compound 1, but does teach assessing NYHA classification
Secondary reference
Caraballo teaches NYHA as a fundamental tool for risk classification of heart failure.
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application, would have found it obvious to assess the NYHA risk classification for a heart failure subject receiving treatment with compound 1. The NYHA score can be used as an assessment of treatment’s efficacy.
Claim(s) 31, 146, 152, 156, 161, 162, 163 is/are rejected under 35 U.S.C. 103 as being unpatentable over Khan et al. (US 2019/0337903)
Scope of prior art
Khan teaches the currently clamed compound (from here on compound 1) in paragraph [0089] and describes utility of the compound as a medicament for treating mitochondria-related disorders including heart failure, diabetes and obesity (paragraph [0090], claims 2 and 3). In claim 2, Khan discloses a method of treating mitochondria-related disorder by administering effective amount of compound 1 to a subject. Khan meets all of the limitations of current claim 8.
Ascertaining the difference
Regarding claim 31:
Khan does not explicitly teach treatment of heart failure in subject who suffer from diabetes or obesity.
Regarding claim 146, 156, 161, 162 and 163:
Khan teaches overlapping ranges but not the specific doses and frequency of administration recited in the claims.
Khan does not teach BMI of the subjects.
Obviousness
Regarding claim 31, Khan teaches that compound 1 is useful in treatment of diabetes and diabetes associated complications. In view of this teaching, it would have been obvious to treat heart failure in a subject with diabetes.
Regarding claim 146, 156 and 161 directed to therapeutically effective amount being a dose selected from 150, 300 or 450 mg/day: Khan teaches dose ranges that encompass the currently claimed dose (paragraphs [0117]-[0118]). Kahn further teaches that determination of therapeutically effective amount is well within the capability of those skilled in the art (paragraph [0115]). A skilled artisan would have found it necessary to determine the optimal safe and therapeutically effective dose in order to practice a method of treating heart failure.
Regarding frequency and duration of administration recited in claims 162 and 163:
In paragraph [0109] Khan teaches administration orally once daily. With regards to duration of treatment, a skilled artisan would have found it obvious to assess the subjects progress and to terminate the treatment when intervention for heart failure is no longer warranted.
Regarding treatment of obesity and BMI of the subject in claim 152. The claimed BMI corresponds to obese subjects. Since Khan teaches treatment of obese subjects it would be obvious to select subjects with the claimed BMI.
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 8, 9, 13, 14, 16, 18, 31, 32, 33, 34, 35, 130, 131, 136, 138, 139, 146, 147, 152, 156, 161, 162, 163 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,618,875. Although the claims at issue are not identical, they are not patentably distinct from each other. Claims of the ‘875 patent is directed to treatment od mitochondria related disorders comprising administration to a subject in need an effective amount of compound 1. All of the currently claimed disorders are within the scope of claims 3 of the ‘875 patent because they are all mitochondria-related disorders. Dependent claims of the ‘875 patent recite the currently claimed disorders such NAFDL, NASH, Diabetes, obesity, cardiovascular disease and heart disease. While claims of the ‘875 patent do not recite specific doses or administration frequency or duration, a skilled artisan would have found it necessary to determine these parameters in order to practice the method of the ‘875 patent. Determining doses and frequency of administration is routine experimentation.
Claims 8, 9, 13, 14, 16, 18, 31, 32, 33, 34, 35, 130, 131, 136, 138, 139, 146, 147, 152, 156, 161, 162, 163 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-8, 10-13, 16, 19-21, 23 of copending Application No. 18/835,578 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Claims of the ‘578 application are directed to a method for weight loss in a subject who has elevated HbA1c level comprising administration of compound 1. The described subject population corresponds to prediabetic and diabetic individuals. The method also describe treatment of NAFDL and reducing liver fat. A skilled artisan would have found obvious to treat the currently claimed diseases by administering compound 1. A skilled artisan would practice the method for wight loss described in claim 1 of the ‘578 application on a subject population that would benefit from wight loss. The subject population in the current claims encompasses subjects with heart failure, cardiovascular disease, NASH and obesity. All of these conditions are well known to be managed by weight loss.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 8, 9, 13, 14, 16, 18, 31, 32, 33, 34, 35, 130, 131, 136, 138, 139, 146, 147, 152, 156, 161, 162, 163 are pending
Claims 8, 9, 13, 14, 16, 18, 31, 32, 33, 34, 35, 130, 131, 136, 138, 139, 146, 147, 152, 156, 161, 162, 163 are rejected
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YEVGENY VALENROD whose telephone number is (571)272-9049. The examiner can normally be reached Mon-Fri 9am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628