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 ).
Status of the Claims
The listing of claims filed 2 October 2024 has been examined.
Claims 1–20 are pending. Claims 4, 9, 10, 13, and 19 are amended.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 18 September 2024 is acknowledged and has been considered.
Objections to the Specification
The abstract of the disclosure is objected to because it recites language referring to the purported merits (“novel”), legal phraseology (“comprising”), and phrases that can be implied (“Disclosed are”).
Appropriate correction is required.
Examiner recommends: “A compound . . . a pharmaceutical composition including the compound . . .”
For guidelines for the preparation of patent abstracts, see MPEP § 608.01(b) (Explaining: The abstract should be in narrative form and avoid legal phraseology (e.g., means, said), terms referring to purported merits of the invention (e.g., new, novel), and phrases that can be implied (e.g., The disclosure concerns, The disclosure defined by this invention). The language should be clear and concise, and not repeat information given in the title. It should not compare the invention with the prior art. The abstract is generally limited to a single paragraph within the range of 50 to 150 words in length.).
Claim Objections
Claims 13 and 19 are objected to for reciting “ENPP1.”
To avoid confusion, acronyms should be defined in the claims, at least in the first instance.
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.
Claims 1–8, 12–17, 19, and 20 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 1 recites, “R6 is a hydrophilic group.”
The term “hydrophilic group” is a relative term because it refers to how readily a substance associates with water. A definition or clear standard or interpretive frame of reference for the term is not provided in the claims or specification. As such, there is no indication that one of ordinary skill in the art would understand what the scope of R6 is. For example, it is unclear whether a hydrogen atom falls within the scope of R6. Therefore, the public would not be informed of the boundaries of what constitutes infringement of a patent issued to the claims.
Claims 2–8, 12–17, 19, and 20 depend from claim 1 and incorporate the issue.
Appropriate correction is required.
Examiner recommends amending claim 1 to incorporate the subject matter of claim 9, which provides definite examples of R6 having written description support in the specification.
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 and 19 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 an unknown number of diseases for an unidentified population of subjects. Claims 13 and 19 recites: “A method for treating an ENPP1-mediated disease . . .” The term “ENPP1-mediated disease” is not defined in the instant specification. The claims therefore encompass treating any disease that is currently known or unknown with respect to having some association with ENPP1. The claims and specification refer to treating solid tumors. No other diseases are mentioned.
The nature of the invention generally relates to the pharmaceutical art and more specifically to a compound of formulae (I-b) or (I-a), pharmaceutical compositions thereof, and methods of administering the compound to a subject in need thereof. The compounds have proliferation inhibitory activity with specific cells (e.g., MDA-MB-231). (Spec., pp.55–60). The claims and specification refer to treating solid tumors. (Id., p.13). Thus, the nature of the invention is sophisticated.
The state of the prior art is discussed in the instant specification, which states: “no ENPP1 inhibitors have been found to be marketed.” (Id., p.2). Accordingly, the art appears to be 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 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 tumors, cGAMP, and ENPP1 inhibitors; an evaluation of in vitro enzymatic inhibition activity for numerous compounds; and evaluation of additional in vitro cell activity for a few, specific compounds. (Spec. pp.1, 2, 55–60).
The existence of working examples relate to in vitro screening of the claimed compounds. (Spec., pp.55–60). There are no examples demonstrating the in vivo treatment of a subject in need thereof, as claimed.
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 in its infancy; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor includes an evaluation of in vitro enzymatic inhibition activity and cell activity for certain compounds; there are no working examples demonstrating the in vivo treatment of a subject in need thereof; 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.
Examiner recommends amending claims 13 and 19 to incorporate the specific disease recited in claims 14 and 20, respectively.
Allowable Subject Matter
Claim 11 is allowed. The claimed compounds are free of the prior art. Close and related prior art includes WO2019/177971 [IDS], which discloses compounds having a similar imidazo-quinoline structural core substituted by an alkylaryl group (Table 1, pp.71–75). The claimed compounds and the compounds in the prior art are distinct from one another because the instantly claimed compounds include a cyclic acetal fused to the quinoline, whereas the prior art compounds have a pair of methoxy groups in the corresponding positions.
Claims 9, 10, and 18 are objected to as being dependent upon a rejected base claim, but would be allowable if the rejections above are sufficiently addressed and/or if the claims are rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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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/JASON M. NOLAN/Patent Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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