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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/05/2025 has been entered.
Status of the Claims
Claims 1-13, 21-24, and 37-40 are pending.
Claims 5-6, 8-9, 12, 13, 21-24, 37-40 are withdrawn.
Priority
Applicant’s claim for benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a national stage entry of and claims priority to Application Serial No. PCT/US20/19458, filed 02/24/2020; and further claims priority to a provisional patent application number 62/809587 filed on 02/23/2019.
Information Disclosure Statement
All references from IDS(s) received 08/20/2021 have been considered unless marked with a strikethrough.
Response to Arguments
Applicant's arguments filed 11/05/2025 have been fully considered but they are not persuasive.
In a final dated 05/05/2025, Claims 1-4, 7, 10, and 11 were examined upon their merits.
In a final dated 05/05/2025, Claims 1-4, 7, 10, and 11 were rejected under 35 U.S.C. 103. Claims 1-2, 4, 7, 10, and 11 were rejected under Improper Markush. In response, the applicant amended claims 1-3 and 10.
With respect to the Improper Markush rejection, the applicant amended claim 1 to recite specific components for the PROTAC. The Applicant also amended claims 2 and 10 to remove chemical structures that do not share a common structural similarity. The Examiner finds that the final structures should not have a common property with the genus structures. The Improper Markush rejection is withdrawn.
With respect to the 103 rejection, the applicant argues that the prior art provided by the Examiner (“Long”) requires the addition or mutation of an unnatural amino acid on the protein of interest (POI). The Applicant also argues that Long teaches the requirement of unnatural amino acids on the POI may be restrictive and are necessary to perform the intended use. The Applicant also argues that Long teaches covalent inhibition of a POI, while the instant application teaches non-covalent protein inhibition and degradation. Finally, the Applicant argues that Long teaches away from the instant invention by the teaching: “However, it remains to be seen how effective systems like BOLT will be in more complex settings. For instance, when the target POI can form hetero-oligomers with other isozymes that can interact with the noncovalent-binding pole of the bifunctional probe, specificity will likely be diminished.”
The Examiner argues that Long is used as a secondary reference. All the deficiencies brought up by the Applicant are taught in the primary reference provided by the Examiner, Bradner. The only limitation Bradner does not teach is the addition of a photoswitchable group within the PROTAC. Long is used as motivation to take a known photoswitchable group and add it to a known bifunctional molecule. A bifunctional molecule would include PROTAC. The instant application teaches a PROTAC with the addition of a photoswitchable group, therefore the instant application is taught by Bradner in view of Long. The Examiner maintains her argument from the previous office action:
The Examiner argues that teachings of Bradner provide a “lead compound.” See Altana Pharma AG vy. Teva Pharm. USA, Inc., 566 F.3d 999, 1008 (Fed.Cir.2009) where a lead compound is “a natural choice for further development efforts.” Since Bradner teaches a lead compound as a bifunctional PROTAC compound, it would be natural to further develop the compound to achieve better targeting. The Examiner argues that Long does teach towards a reasonable expectation of success in modifying the structure taught by Bradner because Long teaches both bi-functional and tri-functional compounds, where PROTAC falls into the bifunctional group and the addition of photoswitch compounds for proximity enhancement fails into the trifunctional group. Therefore, Bradner provides the lead PROTAC that a person skilled in the art would be motivated to modify with a photoswitchable group to improve targeting, as motivated by Long. Since both are well-known in the art, conjugating the two would lead to a reasonable expectation of success. The Examiner notes that with respect to predictability, the field of medicinal chemistry is considered generally unpredictable because, for example, the design of compounds that need to bind to binding pockets. However, within the field, bioconjugate chemistry is considered more predictable because it is the combination and conjugation of two compounds whose structure and function are known in the art and their conjugation to achieve a “two-birds, one-stone” effect would be considered obvious to one skilled in the art at the time. Therefore, the examiner finds the applicants arguments for the 103 rejection against claims 1-4, 7, 10 and 11 is found as not persuasive and the maintained rejection can be seen below.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-4, 7, 10, 11 are rejected under 35 U.S.C. 103 as being unpatentable over Bradner et al. (WO2016105518A1, 2016; US version cited in IDS filed on 8/20/2021; “Bradner”) in view of Long et al. (J. Am. Chem. Soc. 2016, 138, 3610−3622; “Long”)
The rejection applies to the elected specie.
Bradner teaches three out of four of the following components of the elected specie, as required by instant claim 1: the targeting ligand (Claim 19), the E3 ligase as required by instant claim 4 (claims 2-4), the linker as required by instant claim 3 (Claim 10), as well as the conjugation of the compounds with the motivation to produce a bifunctional compound (Claim 1 and Claim 21). Overall, Bradner teaches the design of the PROTAC components of the PHOTAC proposed by the applicant.
Bradner fails to teach the incorporation of a photoswitchable component to the bifunctional compound, leading to the formation of a trifunctional compound.
Long teaches the concept of proximity-directed chemistry of bi- and tri-functional compounds. The toolsets for proximity enhancement were taught in two separate classes. Class I includes bifunctional probes that can either (a) enable the recruitment of two or more distinct biological entities or (b) one pole of the probe serves as an anchor to the protein of interest while the other pole interacts intramolecularly with the same protein of interest (Figure 1). PROTACs are categorized into Class I (Figure 2). Class II describes a new toolset for proximity enhancement: on-demand targeting which enables the reactive entity to be unmasked in situ and targeted to the protein of interest (Figure 1). Photoswitch molecules, such as that required by the instant claim 2, are classified in Class II. Long further teaches the incorporation of photoswitch components into previously bifunctional compounds, for example, photoBOLT (Figure 8).
Therefore, with respect to instant claims 1, 7, 10, 11, it would have been obvious to a person skilled in the art at the time to use a component from Class II, such as a photoswitch, and incorporate it into a known bifunctional compound from Class I, such as a PROTAC.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (A), it would have been prima facie obvious extract the method of Bradner of a PROTAC compound with the components required by the instant claims and incorporate a photoswitch component based on the teaching of Long. Therefore, claims 1-4, 7, 10, 11 would have been obvious to a person who is skilled in the art prior to the effective filing date.
Conclusion
Claims 1-4, 7, 10, and 11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLA MARIA BAUER whose telephone number is (703)756-1269. The examiner can normally be reached Monday-Friday 7:30-5 EST.
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/N.M.B./Examiner, Art Unit 1621