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 .
Status of Claims
Claims 1, 4, 7, and 10 have been amended and claim 8 has been cancelled pursuant to the amendment filed on 21 August 2024. Claims 1-7 and 9-10 are pending.
Priority
This application, filed on 21 August 2024, is a National Stage application of International Application No. PCT/CN2023/078243, filed on 24 February 2023, which claims priority under 35 U.S.C. 119 or 365 to the benefit of China Application No. CN202210173823, filed on 24 February 2022. The certified copy of the foreign application has been received.
Information Disclosure Statement
The information disclosure statements (IDSs) filed on 21 August 2024; 9 January 2025; and 8 June 2026 have been acknowledged and considered.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
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.
Claim 10 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is not enabling for all types of diseases mediated by Janus kinase (JAK). 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.
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. The claim recites: “A method of treating diseases mediated by Janus kinase comprising administering a therapeutically effective amount of the crystal form IIb of Claim 4 to a subject in need thereof.” This method of treatment extends to any and all possible diseases associated with JAK with a vast population of subjects. The specification discloses the scope of diseases extends to variously different classes of diseases: “2-{3-(3-amino-4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1- (benzoyl)azetidin-3-yl}acetonitrile (compound A) belongs to a small molecular inhibitors of the JAK family of non-receptor tyrosine kinase, and its JAK-STAT signaling pathway is closely related to inflammatory cytokines and tumors, and is widely involved in important biological processes such as cell proliferation, differentiation, transfer apoptosis, regulation of immune response and cell homeostasis.” (p. 1). Because the term mediated encompasses direct and indirect interactions with the JAK pathway, the claimed method extends to treating any and/or all diseases involving JAK by administering a therapeutically effective amount of crystal form IIb of compound A.
The nature of the invention generally relates to the pharmaceutical art and more specifically to a polymorph of compound A, a topical pharmaceutical composition comprising a crystal form of compound A, and a method of treating diseases mediated by JAK comprising administering a therapeutically effective amount of a crystal form of compound A to a subject in need. The instant specification states: “It is well known that polymorphs of a drug are of great significance to the physical properties, bioavailability, and quality of the drug as well as the process for preparing the drug. The differences in physical and chemical properties between different crystal forms of a drug affect the stability of the drug. The bioavailability of the same drug may be significantly different due to different crystal forms, and different crystal forms affect the dissolution rate of the drug. Moreover, the difference in surface free energy of different crystal forms will cause different binding forces between crystal particles, which will affect the fluidity, particle uniformity, content uniformity and physical stability of the drug. Therefore, it is necessary to study the crystal forms of a drug” (Spec., p. 2). Thus, the nature of the invention is sophisticated.
The state of the prior art is discussed in a review article which talks about the different JAK inhibitors (JAKinibs) and the conditions treated: “Given the number of cytokines that signal through the JAK–STAT pathway, it is no surprise that Jakinibs have become the first kinase inhibitors used successfully in the treatment of rheumatologic disease. At present, tofacitinib is the only Jakinib approved for autoimmune disease, but several more may soon follow as new data emerge and the development of novel agents continues. Clinical trials are ongoing with various Jakinibs in several autoimmune conditions ranging from rheumatoid arthritis to psoriasis.” (Banerjee et al., p.539). “Jakinibs are poised to change the field of autoimmune and rheumatologic diseases as ongoing basic, preclinical, and clinical research will surely determine the feasibility and benefits of selectivity, optimized dosing, formulation, and patient selection to minimize undesirable off-target effects and maximize clinical efficacy.” (Banerjee et al., p. 540). Table 6 of the review article talks about JAKinibs that are in preclinical and early clinical development to treat asthma, rheumatoid arthritis, and atopic dermatitis (Banerjee et al., p. 539).
Compound A is not mentioned in the review article, but is currently in clinical trials to treat patients affected with Seasonal Allergic Rhinitis (SAR) and Atopic Dermatitis (NCT07146126, NCT06837233, and NCT06587685). In view of the review article and the clinical trials, the state of the prior art is ascending towards discovering novel JAKinibs to improve selectivity, optimize dosing, formulation, and patient selection, while minimizing undesirable off-target effects. Compound A is a JAKinib in clinical trials for SAR and atopic dermatitis. But Examiner is unaware of evidence from the prior art that supports a claim for administering a therapeutically effective amount of a crystal form of compound A to treat all diseases mediated by JAK, like rheumatoid arthritis.
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. Ent. 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 Brane, 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 or veterinary 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 includes background information about JAK as mentioned in factor (A). Also mentioned, are preparations of gel formulations using Examples 1 (compound A crystal form I) or 6 (compound A crystal form IIb) and measuring transdermal rates as shown in Figures 9A-B, which show crystal form I of Compound A has better transdermal performance (Spec., p. 11). The specification does not provide detailed guidance regarding the administration of a therapeutically effective amount of the crystal form IIb to a subject having a disease mediated by JAK, like rheumatoid arthritis.
The existence of working examples relates to preparations of crystal forms I, IIa, IIb and III of compound A, the hydrochloride salt of compound A, and the phosphate salt of compound A (Spec., pp. 6-8, Examples 1-8); transdermal tests (as discussed in factor (F)); long term stability of crystal forms I, IIa, and IIb of compound A (Spec., pp. 9-11); and pharmacokinetic experiments determining the half-life of Examples 1 and 6 via intravenous (solely Example 1), oral, and topical administration (Spec., pp. 11-12). The present disclosure does not provide working examples for methods of treating a subject having a JAK mediated disease comprising administering a therapeutically effective amount of crystal form of compound A, like rheumatoid arthritis.
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. As claimed, the indefinite scope of such diseases is essentially unbound.
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 ascending towards discovering novel JAKinibs and compound A is a JAKinib in clinical trials for SAR and Atopic Dermatitis; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor is limited to preparation of polymorphs, long term stability, transdermal rates, and pharmacokinetic properties of polymorphs of compound A; and does not demonstrate possession of a method of treating any and all diseases mediated by JAK within the scope of the claimed, “method of treating diseases mediated by Janus kinase”; and the quantify of experimentation needed to practice the claimed invention is extensive. Thus, when the evidence is considered as a whole, undue experimentation would be required to practice the full scope of the claimed invention.
While the instant application would provide support for making and using the claimed polymorph compound for the treatment of certain diseases, such as seasonal allergic rhinitis (SAR) and atopic dermatitis, Examiner recommends canceling the claim because the specification does not recite any specific diseases (i.e., there is no written description support for amending the claim to recite specific diseases for which enablement is not an issue).
Allowable Subject Matter
Claims 1-7 and 9 contain allowable subject matter. The closest prior art is CN109867675 (“Zhu”) which discloses a pyrrolopyrimidine derivative compound or a solvate, polymorph, etc. of the same. Zhu also discloses a pharmaceutical composition in preparing medicines for treating JAK kinase mediated diseases (Abstract, translated document of Zhu (“Translated”).
Examples of the compounds prepared are shown in claim 6 (pp. 2-4, original document of Zhu (“Original”)). Compound 6, shown in claim 6 of the Original, is the same compound instantly claimed, and the Translated recites a method of preparing the compound, and the purification was performed on column chromatography to give the compound in 39% yield (p. 12, Step G). The Translated also recites the definition of polymorph is a compound of the invention in different crystal lattice forms (p. 8). While there is a teaching and suggestion of a polymorph of the compound instantly claimed, there is no disclosure in Zhu discussing an explicit polymorph obtained or any X-ray diffraction peaks of any polymorph similar to the ones instantly claimed. There is no teaching nor suggestion to make such polymorphs in the prior art, nor would such teachings and suggestions be expected to produce the same polymorphs I and IIb, as instantly claimed. Accordingly, claims 1-2, 4-5, 7 and 9-10 are both novel and nonobvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHIL CHANDER AGGARWAL whose telephone number is (571)272-7755. The examiner can normally be reached 7am-5pm.
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/SAHIL CHANDER AGGARWAL/Examiner, Art Unit 1623
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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