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 20-24 and 36 are pending in the instant application.
Claims 1-19 and 25-35 have been canceled.
Claims 23-24 stand withdrawn.
Election/Restriction
Applicant has amended the claims such that the elected species of Compound I-33 as a single species of a compound of formula I, as set forth in the restriction requirement filed on October 7th, 2024, no longer reads on the instant claims. As such, the examiner has expanded the search to all compounds of formula I as instantly recited in Claim 20.
Applicant has amended the Claims such that the elected species of psoriasis as a single species of IRAK-mediated disorder is no longer recited in dependent claim 22. As such, Claim 22 is now drawn to a non-elected invention, and is hereby withdrawn.
Information Disclosure Statement
The Information Disclosure Statement filed August 22nd, 2025 has been fully considered by the examiner, except where marked with a strikethrough.
Withdrawn Objections/Rejections
Applicant’s amendment is sufficient to overcome the objection to Claim 20 for not defining the term IRAK. This objection is hereby withdrawn.
Applicant’s amendment is sufficient to overcome the rejection to Claims 20-22 and 35-36 under 35 U.S.C. 102. Claim 22 stands withdrawn. Claim 35 has been canceled rendering the rejection thereof moot. This rejection is hereby withdrawn.
Applicant’s amendment is sufficient to overcome the rejection to Claims 20-22 and 35-36 under 35 U.S.C. 112. Claim 22 stands withdrawn. Claim 35 has been canceled rendering the rejection thereof moot. This rejection is hereby withdrawn.
The following rejections are necessitated by amendment:
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 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 20-21 and 36 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of degrading IRAK4 protein by administering a compound of formula I-2, does not reasonably provide enablement for a method of treating psoriasis or degrading IRAK4 protein by administering any compound of formula I. 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.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
In view of the restriction requirement, the instant invention is drawn to a method of treating psoriasis by administering a compound of formula I.
Breadth of the invention:
The scope of the claimed invention is broad, as it is drawn to the treatment of a specific disorder mediated by IRAK4, psoriasis, by administering a compound of formula I, allowing for myriad combinations of the variables as recited.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Regarding treating psoriasis by administering a compound of formula I, Nunes et. al. (“Targeting IRAK4 for Degradation with PROTACs”, ACS Med. Chem. Lett., 10, 1081-1085, June 14th, 2019; cited on Applicant’s Information Disclosure Statement filed March 15th, 2022; cited in non-final rejection mailed May 6th, 2025) represents the state of the prior art.
At Page 1081, First Column, First Paragraph, Nunes teaches IRAK4 activation has been linked to psoriasis.
At Page 1083, Nunes teaches the compound, I-33 as recited in the instant specification at Page 275) as Compound 8:
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At Page 1083, First Column, Third Paragraph, Nunes teaches administration of compound 8 afforded IRAK4 degradation.
Taken together, Nunes established compound I-33 in the art as a known degrader of IRAK4, and while a link between IRAK4 activation and psoriasis is known in the art, degradation of IRAK4 was not known at the time of filing to predictably treat psoriasis.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Applicant has not provided data demonstrating the efficacy of a compound of formula I as a degrader of IRAK4, nor has Applicant demonstrated the efficacy of a compound of formula I in the treatment of psoriasis.
Beginning at Page 440, with Example 8, Applicant has sufficiently disclosed the experimental protocol demonstrating how compounds are to be tested to demonstrate their efficacy as IRAK4 degraders. With the instant disclosure, however, Applicant has only provided data for compound I-2, recited at Page 270 of the instant specification, demonstrating its efficacy as an IRAK4 degrader in OCI-LY10 cells.
In view of this, Applicant is enabled for a method of degrading IRAK4 by administering a compound of I-2, but is not enabled for doing so with any compound of formula I, as this covers a myriad of possible compounds, and enabling disclosure thereof has not been provided. As previously noted, based on the prior art represented by Nunes, the instant application is enabling for degradation of IRAK4 by administering compound I-33. For clarity of the record, the examiner points out that compound I-33 no longer reads on the instantly recited claims.
MPEP § 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999, F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for the degradation of IRAK4 by administering compounds of formula I, except for compound I-2.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 20-21 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Nunes (“Targeting IRAK4 for Degradation with PROTACs”, ACS Med. Chem. Lett., 10, 1081-1085, June 14th, 2019; cited on Applicant’s Information Disclosure Statement filed March 15th, 2022; cited in non-final rejection mailed May 6th, 2025).
At Page 1083, Nunes teaches the following compound as compound 8:
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This compound reads on a compound of formula I when the variables are defined as follows:
IRAK is
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DIM is
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This compound differs, then, in the definition of L. This compound, however, is homologous to the compounds that would result from defining L as
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, as recited in instant Claim 20.
Per MPEP 2144.09, II. “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)”.
Additionally, at Page 1083, First Column, First Paragraph, Nunes teaches “the linker may be the wrong length to facilitate efficient ternary complex formation.” Further, in the supporting information, at Figure S2, Nunes discloses the following compounds 3B and 3C that were evaluated for IRAK4 degradation:
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Notably, the compounds 3B and 3C, above, lack the ethyl and fluoro groups on the lactam present in the IRAK moiety. While Nunes teaches at Page 1083, First Column, Second Paragraph “shorter four and six carbon atom linkers to VHL were evaluated (see Figure S2). However, these compounds did not afford IRAK4 degradation, presumably as a result of being too short to form a stable ternary complex between IRAK4 and VHL proteins.”
With this in mind, it would have been prima facie obvious for a person having ordinary skill in the art to modify the number of carbon atoms in the linker of Compound 8, taught by Nunes, from 12 caron atoms to 8 carbon atoms to arrive at a compound of formula I defined by IRAK as
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, L as
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, and DIM as
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, with reasonable expectation that this compound would be effective in degrading IRAK4, as Compound 8, above, was known in the art to do so, motivated by the suggestion that the linker was the wrong length. In doing this, a person having ordinary skill in the art would recognize the resulting compound as homologous to Compound 8, and therefore reasonably expect the compound would be effective in degrading IRAK4.
Regarding Claim 36, at the Supporting Information of Nunes, Page 33, Figure S3, Nunes teaches administration of Compound 8 in various concentrations, demonstrating its administration as a pharmaceutical composition as required by Claim 36. Therefore, a person having ordinary skill in the art would expect a homologous compound of Compound 8, as described above, to be suitably administered as part of a pharmaceutical composition.
Conclusion
Claims 20-21 and 36 are rejected.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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/D.J.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624