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 the Claims
Claims 1-23 are pending.
Claims 5, 7, 15-19, and 23 are withdrawn (see election/restriction).
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 CON of a national stage entry of and claims priority to Application Serial No. PCT/US21/55105, filed 10/14/2021; and further claims priority to PRO application number 63/091,897, filed 10/14/2020.
Information Disclosure Statement
All references from IDS(s) received on 12/19/2023 and 03/03/2026 have been considered unless marked with a strikethrough.
Election/Restrictions
Applicant’s election of Group I without traverse in the reply filed on 3/03/2026 is acknowledged. Claim 23 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method of use.
Applicant’s election of Compound 68 without traverse in the reply filed on 3/03/2026 is acknowledged. Claims 5, 7, and 15-19 are withdrawn as not reading on the elected species.
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Claims 1-4, 6, 8-14, and 20-22 will be examined on their merits.
No anticipatory art was found on the elected species. However, the elected species is rejected using an obviousness-type rejection. See 103 analysis below.
Claim Rejection – Improper Markush
Claims 1-4, 6, 8-14, and 20-22 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of targeting ligand is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The structures do not both share a structural similarity or a common use. The Applicant has presented an almost infinite amount of possibilities for the structures and a wide range of different targeting possibilities. For example, MDM4 is a well-known target for treating different types of cancer (Bardot, B. et al. Genes 2017, 8(2), 82; https://doi.org/10.3390/genes8020082) On the other hand, targets as broad as “estrogen receptor” can be targeted for cancer, as well as a variety of other diseases, such as endometriosis (Chantalant, E. et al. Int. J. Mol. Sci. 2020, 21(8), 2815; https://doi.org/10.3390/ijms21082815). These are not only completely different targets, but would also be a treatment of different diseases. Therefore, not only do the targeting ligands have various structural differences, it is the Examiner’s position that the members of the Markush group were separately classifiable and separately patentable.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1)
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims reference FIG 1A-8PPPPP and FIG 10-70 in the Specification for a more thorough list of targeting ligands. The claims cannot reference material in the Specification. The claims must be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). See MPEP 2173.05(s)
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6, 8-14, and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Henderson, J. et al. (WO2020210630A1; claims priority to 62/833,107, filed on April 12, 2019; “Henderson”) in further view of Romero, F. et al. (WO2016086200A1; “Romero”) and Zou, Y. et al. (Cell Biochem Funct. 2019;37:21–30; “Zou”).
Henderson teaches an overlapping genus structure with the E3 ligase of claim 1. Henderson explicitly teaches a structural example of the E3 ligase of the elected species.
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(Henderson, Formula I, where X1-X2 are CH and R1 is N-R)
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(Henderson, Claim 175, 5th Compound)
Henderson fails to teach the compound conjugated to a targeting ligand through a spacer/linker.
Romero teaches the targeting ligand of the elected species. As well as its conjugation to the linker defined in the elected species.
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(The image is obstructed in the application so see similar compound below)
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Romero fails to teach the compound conjugated to an E3 ligase. However, this is a well-known strategy in the art known as PROTAC.
Zou teaches small molecule PROTACS where the PROTAC consists of a ligand E3 ubiquitin ligase conjugated through a linker to a ligand targeted protein (Figure 4).
PROTAC is a popular strategy for developing cancer focused therapeutics (Zou). Therefore, it would be obvious to a person skilled in the art to take a known E3 ligase ligand, as taught by Henderson and conjugate it to a known compound for targeting cancer, such as a CPB inhibitor, though a linker, both of which are taught by Romero.
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 it would have been prima facie obvious to extract the method of PROTAC development as taught by Zou and design a PROTAC using the targeting ligand taught by Romero and the degron taught by Henderson. A skilled artisan would have had a reasonable expectation that conjugating a compound that targets CPB to a E3 ligase ligand would result in a bispecific compound that recruits E3 ligase and results in the degradation of targets associated with caner, such as CPB. Therefore, claims 1-4, 6, 8-14, and 20-22 would have been obvious to a person who is skilled in the art prior to the effective filing date.
Conclusion
Claims 1-4, 6, 8-14, and 20-22 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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clint Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/N.M.B./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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