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 .
Detailed Action
Claims 1-11 and 15-16 are currently pending.
Claim Objections
Claims 10-11 and 15 are objected to because “a compound as claimed in [or according to] claim 1” should be amended to read “the compound…”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 15-16 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 the treatment of MCL-1 associated cancers, does not reasonably provide enablement for non-MCL-1 associated cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
The nature of the invention (1) and breadth of the claims (6)
The nature of the invention and breadth of Claims 15-16 is the treatment of cancer comprising administering compounds of Formula (I).
The state of the prior art (2) and the predictability or lack thereof in the art (3)
Xiang (OncoTargets and Therapy, 2018, 7301-7314) teaches that only a limited amount of cancer is associated with MCL-1 dysregulation; “An analysis of 3,131 cancer specimens has revealed that 36% of breast cancer and 54% of lung cancer specimens exhibit elevated levels of MCL-1 expression” (Page 7301, Para 3). It is unclear how cancers as claimed or specific cancers listed in Claim 16 like lung cancer, which include non-MCL-1 associated forms, would be treated by the present compounds which are MCL-1 inhibitors. One would predict that such compounds would have no effect on the 46% of lung cancers or 64% of breast cancers not associated with MCL-1 levels. Applicant does not explicate how such cancers not associated with elevated MCL-1 would be expected to be treated with the claimed compounds.
The amount of direction or guidance present (4) and the presence or absence of working examples (5)
Applicant demonstrates anti-MCL-1 activity of the claimed compounds (Pages 116-120, Biological Example 2). However, it remains unclear how MCL-1 inhibition would inhibit non-MCL-1-associated cancers embraced by the scope of Claims 15-16.
The quantity of experimentation needed (7)
The quantity of experimentation needed is extremely difficult, novel, and undue experimentation; the ability of the compounds to treat non-MCL-1 associated cancers, encompassed by the broad genus of cancers, is nearly impossible to determine and not at all enabled by the experiments disclosed in the specifications of the application.
The level of the skill in the art (8)
The level of skill in the art is high, even among ordinary artisans. However, there is no expectation that MCL-1 inhibition would affect a disease wherein MCL-1 expression is dysregulated, regardless of the skill of the medical professional practicing the scope of the methods as claimed.
Allowable Subject Matter
The closest art is found in Zhang (US20220041623, cited in 2/08/2024 IDS). Zhang teaches a similar macrocycle to those taught in instant Formula (I) (left). Compound 1 of Zhang (Page 8) (right) differs from Formula (I) in that the alkylenes are attached to the heterobicycle at different points:
PNG
media_image1.png
313
389
media_image1.png
Greyscale
vs.
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media_image2.png
298
298
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Greyscale
.
Zhang does not teach variability in the macrocyclic core at said points of attachment. Further, it is not obvious to form a constitutional isomer of the Zhang compound to yield one of instant Formula (I) because Zhang does not speak to—nor does the art provide guidance regarding—different synthetic routes and kinetics, variable degrees of freedom within the macrocycle, or MCL-1 inhibition potential or activity in vitro or in vivo.
Conclusion
Claims 1-9 are allowable. Claims 10-11 and 15 are objected to. Claims 15-16 are rejected.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 8:30am - 4:30pm EST.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627