DETAILED ACTION
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA or pre-AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 and/or 103 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.
Status of the Claims
The listing of claims filed 30 October 2023 has been examined.
Claims 1–21 are pending. No preliminary claim amendments have been received.
Benefit of Earlier Filing Date
The instant application was filed 30 October 2023; is a continuation application of PCT/IB2022/000251, filed 5 May 2022, and claims the benefit of U.S. Prov. Pat. App. Serial No. 63/185,209, filed 6 May 2021. Applicant’s claim is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 6 February 2024; 23 February 2024; 26 July 2024; 9 January 2025; 5 June 2025; and 4 December 2025 are acknowledged and have been considered.
Claim Objections
Claim 8 is objected to for minor informalities.
Claim 8 recites a list having members thereof labeled (d), (e), and (f). Because claim 8 is an independent claim, the labels should be restarted ((a), (b), etc.).
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 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 MPEP explains the purposes of the definiteness requirement relates to clarity:
The primary purpose of this requirement of definiteness of claim language is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent. A secondary purpose is to provide a clear measure of what the inventor or a joint inventor regards as the invention so that it can be determined whether the claimed invention meets all the criteria for patentability.
MPEP § 2173.02 (emphasis added).
The Federal Circuit has stated the patent drafter is in the best position to improve clarity by resolving any ambiguities in a claim during prosecution:
We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiners demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.
Halliburton v. M-I LLC, 514 F.3d 1244, 1249 (Fed. Cir. 2008).
(i) Claims 1–21 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Independent claims 1 and 8 are directed to a crystalline compound referred to as “Compound A.” The specification discloses Compound A can exist in amorphous form or a plurality of crystalline forms (e.g., Form 1, Form 2, Form 3). (Spec., ¶¶37–39; 163–187). Claims 1 and 8 state, inter alia, that crystalline Compound A is characterized by the XRPD patterns in Figure 1 and Figure 7, respectively. Those XRPD patterns are different, which means the claims are directed to different forms of Compound A. The claims, however, do not state which form of Compound A is claimed. Because claims must stand alone (i.e., separate from the specification), one of ordinary skill in the art would not be reasonably apprised as to which of the one or more forms of Compound A the claims are directed to.
Claims 2–7 and 9–21 directly or indirectly refer to claims 1 or 8; and each claim fails to resolve the ambiguity.
Appropriate correction is required.
Examiner recommends amending the claims to specify which crystalline form is claimed.
(ii) Claims 14, 16, and 17 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 14 recites, “fat-related disorder.”
Claim 16 recites, “disorder associated with fat accumulation.”
Claim 17 recites, “fibrosis associated with a second disease or disorder.”
Each claim recites a relative term that renders the claim indefinite. The terms are not defined by the claim, and the specification does not provide a definition or a standard for ascertaining which disorders are “related” to fat or “associated” with fat accumulation; nor is there a standard for distinguishing fibrosis that is or is not “associated with a second disease or disorder.” For these reasons, one of skill in the art would not be reasonably apprised of the scope of the claimed invention or how to avoid infringement.
Appropriate correction is required.
Examiner recommends canceling claim 14; and deleting or amending “a disorder associated with fat accumulation” and “fibrosis associated with a second disease or disorder” in claims 16 and 17, respectively.
Claim Rejections - 35 U.S.C. § 112
The following is a quotation 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.
Claims 13–15 are rejected under 35 U.S.C. § 112(a) because 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 the claims.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” . . . These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The breadth of the claim is broad in scope, as it extends to treating or preventing an unknown number of diseases for an unidentified population of subjects.
Claim 13 recites: “A method of treating a disease or disorder in a subject . . .” The scope of claim 13 covers any disease or disorder. Claim 14 recites, “the disease or disorder is a fat-related disorder.” The scope of claim 14 is indefinite, as noted above. Claim 15 recites, “the fat-related disorder is . . . a cardiovascular disease, a reproductive disease, a neurological disease, a psychiatric disease, a rheumatological disease, or an orthopedic disease.” The scope of claim 15 covers numerous classes of disease. Accordingly, the claims are directed to a method of treating any disease, an indefinite number of diseases, and a plurality of generic classes of diseases.
The specification defines “treating” in a manner that includes “preventing the onset of the disease”:
“Treating” or “treatment” encompasses administration of Compound A, or a pharmaceutically acceptable salt thereof, to a mammalian subject, particularly a human subject, in need of such an administration and includes (i) arresting the development of clinical symptoms of the disease, (ii) bringing about a regression in the clinical symptoms of the disease, and/or (iii) prophylactic treatment for preventing the onset of the disease.
(Spec., ¶97) (emphasis added).
The nature of the invention generally relates to the pharmaceutical art and more specifically to a method of treating diseases with a crystalline form of Compound A. The diseases include a cardiovascular disease, a reproductive disease, a neurological disease, a psychiatric disease, a rheumatological disease, an orthopedic disease, etc. Thus, the nature of the invention is sophisticated.
The state of the prior art appears to be developed for a method of treating certain diseases with Compound A, but undeveloped for treating or preventing the full scope of diseases encompassed by the claimed methods.
Generally, in order to treat a disease, one of skill in the art must identify a biological target for affecting the disease, demonstrate a first drug candidate some way modulates the normal processes of the biological target, and demonstrate that a subject would benefit from such modulation without detrimental side effects. Typically, the process includes in vitro laboratory screening, in vivo testing, and clinical testing. Once that process has been successfully completed by the first drug candidate, subsequent drug candidates can benefit from the established proof of concept if a substantial correlation can be established between the first drug candidate and the subsequent drug candidates.
Reports from clinicaltrials.gov and a Raziel Therapeutics brochure submitted with the IDSs show Compound A has been investigated in clinical trials for lipedema, Dercum’s disease, lipoma, obesity, and fat reduction. Thus, a method of treating those diseases with Compound A is relatively developed.
In order to prevent a disease, one of skill in the art would need to identify the subjects likely to acquire such as disease, carry out the claimed invention (e.g., administer the claimed compound/composition), and demonstrate the subject did not have any cells infected by the pathogen and/or demonstrate the subject did not develop the disease as a result of the administration of the compound/composition.
Examiner is unaware of evidence in the prior art that supports a claim for preventing a disease with Compound A. The corresponding state of the prior art is in its infancy.
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art is generally unpredictable. The relevant art requires each potential drug candidate to be assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18, 24 (CCPA 1970). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor is limited to generic statements with respect to the claimed methods. The specification lists diseases and states one of ordinary skill in the art would be able to determine the amount of Compound A to administer as well as the subject to be treated. (Spec., ¶¶113–126). The specification further states the biological effect of the treatment can be monitored and adjusted as needed. (Id.).
The existence of working examples is limited to the synthesis of Compound A, preparation of different crystalline forms thereof, and characterization of the same. There are no examples demonstrating the claimed methods.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure is extensive, as it includes in vitro and in vivo screening for each specific disease or disorder encompassed by the claims, which is a significant but indefinite number of diseases. Therefore, an extensive amount of experimentation would be needed to use the claimed invention based on the disclosure.
Scope of Enablement Conclusion
In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a person having ordinary skill in the art to use the full scope of the claimed invention. The breadth of the claims is broad in scope; the nature of the invention is sophisticated; the state of the prior art is in its infancy for preventing any disease and is being developed for treating for lipoma, lipedema, Dercum’s disease, obesity, and fat reduction; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor is limited to generic statements with respect to the claimed methods; there are no working demonstrating the claimed methods; and the quantify of experimentation needed to practice the claimed invention is extensive. Thus, when the evidence in the Wands factors is considered as a whole, undue experimentation would be required to practice the full scope of the claimed invention.
Examiner recommends: (i) amending the claims to state a subject having a specific disease or disorder to overcome the issue of preventing; and (ii) further amend the claims to recite only specify diseases for Compound A.
Claim Interpretation
Claim 1 is directed to crystalline Compound A characterized by at least one of the options (a)–(i). Options (g), (h), and (i) relate to “an unchanged XRPD after storage . . . for 7 days,” and combinations thereof.
Courts have held that expressions of an intended result in a claim are not given much patentable weight. MPEP § 2111.04.
In the context of claim 1, the limitations in options (g) and (h), or a combination thereof (option (i)), are not given much patentable weight because they are directed to an intended or desired result of the claimed invention after it has been stored for 7 days.
Claim Rejections - 35 U.S.C. § 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.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966); MPEP § 2141(II).
Claims 1, 11, and 12 are rejected under 35 U.S.C. § 103 as being unpatentable over WO2016/203468 (“Ben-Sasson”) [IDS].
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
Ben-Sasson discloses a composition comprising pharmaceutical salts of Compound A as an active agent. (Ben-Sasson, p.9).
The pharmaceutical salt can be based on hydrochloride. (Id., p.16).
The pharmaceutical salt is for use in mammals. (Id).
The composition can include pharmaceutical auxiliaries [excipients]. (Id., p.14).
The composition can be formulated for paternal administration. (Id., p.15).
Ben-Sasson discloses the compounds may have the ability to crystalize in multiple forms, known as polymorphs, and such polymorphs are within the scope of the compound. (Id., p.13).
Ascertaining the differences between the prior art and the claims at issue
Ben-Sasson does not disclose a specific polymorphic form of Compound A.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill is discussed in the enablement rejection above. That discussion is incorporated herein by reference.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application does not include evidence of non-obviousness.
The question of obviousness
Based on the above factors, it would have been obvious for a person having ordinary skill in the art prior to the filing of the instant application to combine the teachings of Ben-Sasson to arrive at the claimed crystalline form of Compound A that is capable of being characterized by options (g), (h), and (i) because Ben-Sasson discloses the compound, pharmaceutical salts thereof, and polymorphs thereof. The differences between the claimed invention and the disclosures in Ben-Sasson are related to a desired result (i.e., future properties of the polymorph), which is accorded minimal patentable weight. One of ordinary skill in the art would have been motivated to modify apply the disclosures in Ben-Sasson to obtain the most stable polymorph of Compound A. There would have been a reasonable expectation of success at arriving at the claimed invention because the structural features are disclosed in Ben-Sasson and the methods of preparing different polymorphs of Compound A (e.g., crystallization) are routine in the art.
Examiner recommends deleting options (g) and (h) from claim 1.
Conclusion
No claims are allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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/J.M.N./Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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