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 .
Status of Claims
Claims 1-20 are pending in the instant application.
Domestic Benefit
Acknowledgement is made of Applicant’s claim for domestic benefit based on U.S. Provisional Application No. 63/325,860, filed on March 31st, 2022. Claims 1-20 are fully supported by this application and will be evaluated with an effective filing date of March 31st, 2022.
Information Disclosure Statement
The Information Disclosure Statement filed December 18th, 2024 has been fully considered by the examiner, except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a method of treating myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) comprising administers a tropane CCR5/CCL5 interaction inhibitor.
Breadth of the invention:
The scope of the claimed invention is broad. Despite being directed to treating ME/CFS, the invention is drawn to treating ME/CFS via administering any tropane CCR5/CCL5 interaction inhibitor. The scope of this limitation encompasses not only compounds that are presently classified as tropane CCR5/CCL5 interaction inhibitors, but would extend to compounds discovered later that are classified as tropane CCR5/CCL5 interaction inhibitors, or compounds that are presently known, but later classified as tropane CCR5/CCL5 interaction inhibitors. Can the Applicant simply “reach through” and obtain patent protection for a method of treatment comprising administering compounds that are discovered years from now or compounds presently known that are later classified as tropane CCR5/CCL5 interaction inhibitors?
Dependent Claim 2 more narrowly defines the scope of tropane CCR5/CCL5 interaction inhibitors with the compound of formula IA. This compound core depicted with specific substituents represents a narrow subgenus for which applicant has provided sufficient guidance to make and use.
State of the prior art and predictability in the art:
With regard to the treatment of ME/CFS, Cortes Rivera et. al. (“Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review”, Diagnostics, 2019; hereinafter referred to as Cortes Rivera) represents the state of the prior art.
At the Abstract, Cortes Rivera states, “At the moment, there are no specific pharmacological therapies to treat the disease,” thereby underscoring the lack of predictability in the art of treating ME/CFS.
Further, at Page 18, First Paragraph under “8. Management”, Cortes Rivera states “In the pharmacological approach to the management of ME/CFS, trials have had a poor external validity, and have proven to be inconsistent and inconclusive.” Of 20 drug therapies identified from 26 studies, Cortes Rivera teaches “Eleven medications were shown to be either slightly, mildly, or moderately effective in their respective study groups.” Cortes Rivera teaches individual studies of such drugs in clinical trials yielded inconclusive results.
At Page 21, Third Paragraph, Cortes Rivera teaches “Due to the unclear aetiology, diagnostic uncertainty, and the resultant heterogeneity of the ME/CFS, there are no established treatment recommendations in the clinical practice.” Further, at the Fourth Paragraph, Cortes Rivera states, “There has also been insufficient evidence of the effectiveness of pharmacological, supplementary, complementary, and other interventions.” Taken together, this establishes a lack of effective and predictable treatment for ME/CFS.
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
At Page 21, Lines 13-18 of the instant specification, a treatment study is described in which 50 ME/CFS patients and 25 controls are enrolled to receive placebo. Applicant states that subjects will be treated for 6 weeks with a combination of maraviroc and a statin, and that response of biomarkers of the immune system and subjective symptom scores are evaluated. No results from such a study, however, have been provided. Without any data demonstrating treatment of ME/CFS, the method claimed herein is speculative, and the instant disclosure does not sufficiently enable the method claimed herein.
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. As referenced above, a person having ordinary skill in the art would need to not only identify and/or develop suitable metrics by which to determine the suitability of administering a tropane CCR5/CCL5 interaction inhibitor in treating ME/CFS, but also to employ these metrics, with no assurance of success.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
The specification fails to provide enough support for the instantly claimed method of treating ME/CFS.
Genentech Inc. v Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “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 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 and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage in undue experimentation to determine the efficacy of the instantly claimed method of treating ME/CFS, with no assurance of success.
Claim 12 is 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 administration of a statin selected from the instantly recited group, does not reasonably provide enablement for administration of prodrug derivatives thereof. 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 and use the invention commensurate in scope with these claims.
Nature of the invention:
As above, the invention is drawn to the treatment of ME/CFS comprising administration of a tropane CCR5/CCL5 interaction inhibitor in combination with a statin.
Breadth of the invention:
The scope of the claimed invention is broad. In addition to the aforementioned considerations of breadth with respect to administration of compounds classified as a tropane CCR5/CCL5 interaction inhibitor, the recitation of “prodrug derivatives” encompasses a wide array of compounds readily envisaged by a person having ordinary skill in the art.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
State of the prior art and predictability in the art:
With respect to the use of prodrugs, Walther et. al. (“Prodrugs in medicinal chemistry and enzyme prodrug therapies”, Advanced Drug Delivery Reviews, 2017; hereinafter referred to as Walther) represents the state of the prior art.
At Page 66, Table 1, Walther establishes the motivation by which a person having ordinary skill in the art might select a prodrug including poor aqueous solubility, poor absorption from the gastro-intestinal tract into the blood, and poor rates of cell entry of the parent drug compound. Additionally, at the Last Paragraph of Page 66, Walther teaches design strategy for a prodrug depends on the structural features of the parent drug molecule and availability of the appropriate chemical functionalities that can be used to mask pharmacodynamic activity of the drug through the attachment of a modifying group. Typically, an enzymatic process is relied upon for drug release.
At Page 67, Last Three Paragraphs, Walther teaches esters are common moieties installed for the generation of a prodrug due to the ubiquity of esterases in the body.
In the instant case, due to the breadth of the statins that read on the instant claim, a person having ordinary skill in the art, based on the instant disclosure, lacks the direction to understand which prodrugs are suitably employed in the context of the instant invention, nor would it be readily understood the motivation for doing so.
The amount of direction provided and working examples:
Though the instant specification generically mentions the use of prodrugs of the instantly claimed statins, no specific examples are disclosed in which a combination has been utilized employing a prodrug of a statin. Additionally, no specific examples of prodrugs are put forth in the instant specification.
Within the specification, “specific operative embodiments or examples must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F. 2d 1557, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for the broadly claimed prodrug derivatives of a statin as instantly claimed.
Claims 2-9 and 12 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 tropane CCR5/CCL5 interaction inhibitors described by the formula I or IA and pharmaceutically acceptable salts thereof, does not reasonably provide enablement for solvates of compounds of formula I or formula IA. 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 and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a method of treating a subject for Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) comprising administering a CCR5/CCL5 interaction inhibitor of formula I or formula IA, pharmaceutically acceptable salts, or solvates thereof.
Breadth of the invention:
The scope of the invention is broad. While the invention is directed toward treating ME/CFS, a person having ordinary skill in the art would readily envisage a plethora of solvates of compounds of formula I or formula IA that could be generated to read on the limitations as instantly recited.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
The amount of direction provided and working examples:
Applicant has provided no working examples of any solvates of compounds of formula I or formula IA. A person having ordinary skill in the art would not be guided by the instant disclosure to understand which solvates of compounds of formula I or formula IA are suitable use in the context of the instantly disclosed invention, nor would they readily understand based on the instant disclosure the motivation for utilizing a solvate of a compound of formula I or formula IA.
Within the specification, “specific operative embodiments or examples must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F. 2d 1557, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for the broadly claimed prodrug derivatives of a statin as instantly claimed.
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.
Claim 18-19 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.
Regarding claims 18-19, the term "preferably" renders the claims indefinite because it is unclear whether the limitation(s) following the term are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Volinsky et. al. (US 2015/0050241 A1; cited on Applicant’s Information Disclosure Statement filed December 18th, 2024; hereinafter referred to as Volinsky) as evidenced by CAS Registry File 376348-65-1 (entered into STN December 18th, 2001; hereinafter referred to as CAS Registry File).
At Page 25, Paragraph [0317], Volinksy teaches compounds and pharmaceutical compositions according to the present invention with the administration of additional antiviral agents can be used for the treatment of myalgic encephalomyelitis/chronic fatigue syndrome.
Regarding Claims 1-10, at Page 18, Paragraph [0252], Volinsky teaches additional antiviral agents suitable for use with the compounds and pharmaceutical compositions taught includes maraviroc, as recited at instant Claims 8-9. CAS Registry File teaches maraviroc has the structure:
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354
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This compound reads on a compound of the formula instantly recited at Claim 2 when the variables are defined as follows:
R1 is 4,4-difluorocyclohexyl.
R2 is phenyl.
While Volinsky teaches administration of maraviroc with at least one other additional compound, this still reads on the instantly calimed method, as the instant method is drawn to treatment of ME/CFS comprising administration of a tropane CCR5/CCL5 interaction inhibitor. Per MPEP 2111.03, I., “The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004).” Therefore, the method taught by Volinsky reads on the method recited, for example, at instant Claim 1.
Claim Rejections - 35 USC § 103
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.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Volinsky et. al. (US 2015/0050241 A1; cited on Applicant’s Information Disclosure Statement filed December 18th, 2024; hereinafter referred to as Volinsky).
At Claim 30, Volinsky teaches a pharmaceutical composition that comprises antiviral agents selected from the group consisting of compounds including trichostatin A and maraviroc.
With respect to the instant Claim 20, the recitation of “for use in treating a subject for ME/CFS” is a statement of intended use that does not result in a structural difference between the instantly claimed kit and the prior art. Per MPEP 2111.02, II., “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”
Volinsky, then, teaches trichostatin A and maraviroc as antiviral agents. Per MPEP 2144.06, “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.” Therefore, a person having ordinary skill in the art would have found it prima facie obvious to make a kit comprising a statin and a tropane CCR5/CCL5 interaction inhibitor given their status in the art as serving a common purpose of acting as antiviral agents.
Conclusion
Claims 1-20 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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/D.J.B./Examiner, Art Unit 1624
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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