DETAILED ACTION
Notice of 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 the Claims
Claims 1-8, 10-11 and 13-16 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
Allowable Subject Matter
Claims 1 and 10-11 are ALLOWED.
The claims are drawn to a compound of formula (I) (claim 1) and compositions thereof (claim 10), in particular for administration by inhalation (claim 11).
The compounds have been searched and are free of the art and non-obvious. And since the compounds and compositions thereof contain written support and are enabled, the claims are ALLOWED.
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 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 13-14 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a method of treating fibrosis (including, e.g., pulmonary fibrosis, idiopathic fibrosis, etc.), is not considered enabled for treating any disease, disorder or condition mediated by ALK5 signaling including any disease, disorder or condition that involves fibrosis. 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 these claims.
The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below
Nature of the Invention and Breadth of the Claims: the claimed invention is drawn to methods of treating a disease, disorder or condition mediated by ALK5 signaling in a mammal (claim 13), more specifically a disease, disorder or condition that involves fibrosis (claim 14), the method comprising administering to a subject in need thereof a pharmaceutical composition comprising a compound of formula (I). The treatment of any disease, disorder or condition is considered to be complex. In the instant case, this complexity is exacerbated by the broadness of the claims, which are not directed to single disease or a single class of diseases, but which embrace the treatment of any disease, disorder or condition mediated by ALK5 signaling and any disease, disorder or condition that involves fibrosis.
The State of the Prior Art and the Level of Predictability in the Art: the ALK5 signaling pathway is implicated in a number of unrelated conditions, including fibrosis (Mansour et al (Bioorg Chem 147:107332, 2024)) as well as cancers (Arai et al (J Med Chem 68:7106-7118, 2025)), cerebral ischemia/reperfusion injury (Zhang et al (Cell Death and Disease 10:360, 2019)), neurogenesis and Alzheimer’s disease (He et al (Nat Neurosci 17:943-952, 2014)), and so on. To date, there is no known agent that can treat fibrosis (including any disease, disorder or condition that involves fibrosis) as well as any cancer, stroke, neurogenesis, Alzheimer’s disease, and the like.
The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the Specification demonstrates that approximately 50 compounds within formula (I) exhibit activity as antagonists of the ALK5 receptor. However, the Specification provides no evidence that any compound can treat any condition, including fibrosis (including any disease, disorder or condition that involves fibrosis) as well as any cancer, stroke, neurogenesis, Alzheimer’s disease, and the like..
Amount of Experimentation Necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to methods of treating a disease, disorder or condition mediated by ALK5 signaling in a mammal (claim 13), more specifically a disease, disorder or condition that involves fibrosis (claim 14). Since treating any condition is considered to be extremely complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of the claims – in particular with respect to the disclosure – since the claims are directed to the treatment of any disease, disorder or condition mediated by ALK5 signaling and any disease, disorder or condition that involves fibrosis, which would embrace the treatment of fibrosis (including any undefined disease, disorder or condition that involves fibrosis) as well as any cancer, stroke, neurogenesis, Alzheimer’s disease, and the like. Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented could not reasonably predict which compound encompassed by formula (I) might find use in the treatment of the hundreds of various diseases embraced by the claims. Thus, in order to carry out the instantly claimed invention, the skilled artisan (at minimum) would have test each of the hundreds of compounds embraced by formula (I) in the treatment of hundreds of diseases, disorders and conditions embraced by the claims, with virtually no expectation of success. That is, the only way one skilled in the art is enabled to use the entire scope of the claim based on the instant disclosure entails undue experimentation.
To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
Claims 2, 4-5 and 7-8 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 a compound of formula (I) having the following structure:
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wherein A is selected from:
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Claims 2, 4-5 and 7-8 depend from claim 1 wherein claim 2 (which is representative of claims 4-5 and 7-8) recites “[t]he compound of formula (I)… according to claim 1, wherein A is group A1
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represented by formula (Ia)
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The claim is indefinite because it indicates that in formula (I), as recited by claim 1, the variable A is group A1 wherein said group A1 is represented by formula (Ia).
Claim 2 should recite “[t]he compound or pharmaceutically acceptable salt thereof according to claim 1 represented by the formula (Ia)… ”
Claims 4-5 and 7-8 should be similarly amended.
Claim Objections
Claims 3, 6 and 15-16 are objected to as depending from a rejected base claim, but would be ALLOWABLE if rewritten in independent form including all the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611