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 .
Priority
The instant application is a 371 National Stage Entry of PCT/US2021/064651 filed on December 21, 2021 which claims benefit to domestic provisional application No. 63/128,967 filed on December 22, 2020.
Status of Claims
Acknowledgement is made of original (1, 27, 31, 35, 38), amended (2, 4, 6, 9, 11, 14, 17, 20, 22-24, 28, 30, 32, 34), and cancelled (3, 5, 7-8, 10, 12-13, 15-16, 18-19, 21, 25-26, 29, 33, 36-37) claims filed on April 8, 2024. Claims 1-2, 4, 6, 9, 11, 14, 17, 20, 22-24, 27-28, 30-32, 34-35, 38 are pending in instant application.
Information Disclosure Statement
The information disclosure statement filed on October 6, 2023 has been considered.
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 34, 35 and 38 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 treating defined diseases and disease classes in claims 35 and 38, does not reasonably provide enablement for “treating an IRAK4 mediated disease”. 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.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the nature of the invention,
2- the breadth of the claims,
3- the state of the prior art,
4- the predictability of the art,
5- the amount of direction or guidance provided
6- the presence or absence of working examples,
7- the quantity of experimentation necessary, and
8- the relative skill of those in the art.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Undue experimentation is required by one skilled in the art to determine enablement of the instant disclosure as claimed due to the following:
The nature of the invention (1) and the breadth of the claims (2)
The nature of the invention and breadth of claim(s) is the treatment of a disease mediated by IRAK4 broadly (claim 34) or those diseases specifically listed in claims 35 and 38.
Page 34 of the specification defines “treatment” as:
the management and care of a patient for the purpose of combating the disease, condition, or disorder and includes the administration of a compound of the present invention to obtaining desired pharmacological and/or physiological effect. (see instant spec. at p. 34 lines 16-19).
The specification does not define IRAK4 mediated disease.
The state (3) and predictability (4) of the art
MPEP § 2164.05(a) states if a publication demonstrates that those of ordinary skill in the art would not find that a particular invention was not enabled years after the filing date, the publication would be evidence that the claimed invention was not possible at the time of filing.
Bennett et. al.1 teaches in regards to unpredictability, IRAK signaling is not fully understood and the "conspicuous gaps in the literature cast doubt as to whether extant IRAK inhibitors are fully optimized for clinical use" (see Bennett at p. 16 Conclusion).
Bennett teaches in regards to treatment with IRAK4 inhibitors, current IRAK4 inhibitors are under clinical investigation for treating rheumatoid arthritis, Non-Hodgkin's lymphoma, Waldenstrom's macroglobulenemia, atopic dermatitis, and myelodysplastic syndrome (see Bennett at p. 15 Table 1).
Further, regarding claim 34, a method of treating an IRAK4 mediated disease includes diseases and conditions not yet discovered and not yet discovered to be responsive to inhibition of IRAK4. It would certainly require undue experimentation to discover the enabled embodiments encompassed by claim 34.
The prior art provides enablement for treating inflammatory diseases and hematological cancers.
The amount of direction or guidance provided (5) and the presence or absence of working examples (6)
The specification provides the following embodiments:
Inhibition assay, IC50 values determined for inhibiting IRAK4, notably all 97 species tested (see instant spec. at p. 166 Example 1 and at pp. 173-175 Table)
Permeability assay, MDRI-MDCK efflux ratios determined, notably 96 species tested (see instant spec. at pp.166-167 Example 2 and at pp. 173-175 Table).
Solubility assay, solubility determined in ug/mL at a pH 6.8, notably 79 species tested (see instant spec. at pp. 168-169 Example 3 and at pp. 173-175 Table).
Blood-brain barrier testing, in vivo PK experiment, Kpuu values determined, notably only 28 species tested (see instant spec at pp. 169-173 Example 4 and at pp. 173-175 Table)
IRAK4 SPR binding assay, IRAK4 binding half-lifes determined notably only 18 species tested (see instant spec. at p. 173 Example 5 and at pp. 173-175 Table).
The specification provides enablement for inhibiting IRAK4 in vitro.
Nowhere in the specification is it explained how such cancers or any other disease listed in claims 35 and 38 are to be prevented through the administration of the claimed compounds. Also, it is not explained in the art or applicant’s disclosure how the following diseases are ameliorated or their symptoms reduced by the method of claim 34.
Therefore, the full scope of treatment in the methods of claim(s) 34, 35, and 38 are not enabled.
The quantity of experimentation necessary (7) and the relative skill of those in the art (8)
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. Because of the unknown predictability in the art (as discussed above) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that compounds of Formula I could be used as a treatment for an IRAK4 mediated disease or those diseases specifically listed in claims 35 and 38.
Brenner v. Manson states "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (Brenner v. Manson 383 U.S. 519, 536, 148 USPQ 689, 696 (1966), cited in Genentech Inc. vs. Nova Nordisk 42 USPQ 2d 1001, Fed. Circuit 1997).
As noted above, little experimentation provided is drawn to treatment of diseases listed in claims 35 and 38. A review of the state of the art fails to reveal that IRAK4 inhibitors are useful as therapeutic treatment as claimed (e.g. any cancer). Determining if compounds of Formula I would be therapeutic for any particular disease state would require careful analysis and replicability of a composition comprising a compound of Formula I, formulation into a suitable dosage form, assay testing to correlate clinical efficacy, identifying off-targets, subjecting to animal trials, and subjecting to clinical trials.
All this is undue experimentation given the limited guidance and direction provided by Applicants.
Conclusion
Accordingly, the inventions of claims 34, 35, 38 do not comply with the enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Suggested Amendment
Examiner suggests cancelling claims 35 and 38, and amending claim 34 to include fully defined diseases and enabled disease classes:
A method of treating an IRAK4 mediated disease in a subject comprising administering to the subject a compound or a pharmaceutically acceptable salt thereof of claim 1, wherein the IRAK4 mediated disease is selected from: rheumatoid arthritis, atopic dermatitis, Non-Hodgkin's lymphoma, and myelodysplastic syndrome.
Allowable Subject Matter
Claims 1-2, 4, 6, 9, 11, 14, 17, 20, 22-24, 27-28, 30-32 allowed.
The following is an examiner’s statement of reasons for allowance:
The closest prior art appears to be WO 2017/009798 A1 to Gummadi et. al.2
Gummadi teaches IRAK4 inhibitors such as Example 55 (see Gummadi at Abstract and at p. 99).
Gummadi Example 55
Instant Formula I
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74
167
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111
249
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The core of Gummadi’s IRAK4 inhibitors varies in several places:
amide connectivity
cyclopropyl connectivity
pyridine vs 2-pyridone
instant Z identity
ether substituent
While any one of these changes might be obvious to an artisan, no motivation or suggestion was found to make all such changes.
Conclusion
Claims 1-2, 4, 6, 9, 11, 14, 17, 20, 22-24, 27-28, 30-32 allowed.
Claims 34-35, 38 rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Bennett et. al. "IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies" Current Opinion in Hematology, 2022, 29, 1, 8-19. DOI: 10.1097/MOH.0000000000000693 Hereinafter Bennett.
2 Cite No. 23 in the IDS filed October 6, 2023. Hereinafter Gummadi.