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 .
Claims 1-10, 13-21, 38-41, 49 and 50 are pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on February 18, 2026 is acknowledged.
Claims 49 and 50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 18, 2026.
Claims 1-8, 13-21 and 38-41 are rejected as being drawn to an improper Markush group. The recited compounds, while possessing a common utility, differ widely in structure and are not art-recognized equivalents and are thus, independently distinct for the reasons set forth in the restriction. The Markush group represented by Targeting Moiety, Linker, Protease Ligand and E3 Ligase Ligand which are structurally dissimilar renders the claim clearly improper.
The Applicant’s indicated in their elected species consist of compounds of Formula (IB) with the variables as set forth in the response. It is by this election that the compounds have been searched. That is the compounds have only been searched to the extent that the E3 ubiquitin ligase ligand is VHL032 and the linker contains a phosphorus atom.
Specification
The disclosure is objected to because of the following informalities which are just a few found by the Examiner:
The specification fails to provide a description for Figure 5C;
Page 21, line 3 states Figures 34A-34E, however there is a Figure 34F mentioned in line 12; and
Page 35, line 12, contains a patent number which is missing a number, i.e. 5,64,562.
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See page 113, line 23; page 169, line 26; and page 187, line 14.
The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
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 1-10, 13-21 and 38-41 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 species set forth in example 4
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, does not reasonably provide enablement for the magnitude of compounds set forth in formula Targeting Moiety – Linker – Protease Ligand or E3 Ligase Ligand. 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/or use the invention commensurate in scope with these claims.
In evaluating the enablement question, several factors are to be considered. In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988); Ex parte Forman, 230 USPQ 546. The factors include: 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, and 7) the quantity of experimentation needed.
The nature of the instant invention has claims, which embrace compounds where the E3 Ligase Ligands is CRBN
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; C1
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; or VHL
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.
The E3 Ligase Ligand is described in the specification as follows: an E3 Ligase Ligand that binds cereblon is
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528
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440
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and
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; where the E3 Ligase Ligand that binds a Von Hippel-Lindau (VHL) is
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516
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and
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; where the E3 Ligase Ligand that binds an inhibitor of apoptosis protein (IAP)
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158
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; where the E3 Ligase Ligand that binds murine double minute 2 (MDM2)
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; and where the E3 Ligase Ligand is based on phthalic acid or 3-aminophthalic acid as set forth in claim 13.
The instant specification teaches 26 examples where E3 ligase ligand part is CRBN
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; C1
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; and VHL
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, i.e. R-C-N1 [0171], R-C-N2 [0171], R-C-A1 [0171], R-C-A2 [0171], Table 3 LEF1 OP-C1, LEF1 OP-C2, LEF1 OP-C3, LEF1 OP-V1, LEF1 OP-V2, LEF1 OP-V3, LEF1 Biotin-OPs, LEF1 FITC-OPs, ERG OP-C1, ERG OP-C2, ERG OP-C3, ERG OP-C-N1, ERG OP-C-N2, ERG OP-C-A1, ERG OP-C-A2, ERG OP-V1, ERG-OP-V2, ERG-OP-V3, ERG Biotin-OPs, ERG Control OP and LEF1 Control OP; and one additional species found in Table 4 ERG OP-C-P1.
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. In addition to a magnitude of possible substitutions for E3 Ligase Ligand which is just a small portion of the compounds of Formula (IB) Targeting Moiety – Linker – Protease Ligand or E3 Ligase Ligand. The magnitude of possible combinations is not described in the disclosure in such a way that one of ordinary skill in the art would know how to prepare the various compositions suggested by claims 1-10, 13-21 and 38-41. Where are the starting materials for the preparation of compounds where each of the suggested E3 ligase ligand in claims 1, 13 and 38 or the suggested linkers in claims 4-8, 14-18, etc.
The Protease ligand and E3 ligase ligands described in the specification (Table 3) includes CRBN
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and VHL
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; and the linkers are
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and
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.
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.
In view of the lack of direction provided in the specification regarding starting materials, the lack of working examples, and the general unpredictability of chemical reaction, it would take an undue amount of experimentation for one skilled in the art to make the claimed compounds and therefore practice the invention. To be enabling, the specification of a patent must teach those skilled in the art how to make and use the scope of the claimed invention without undue experimentation. The applicants are not entitled to preempt the efforts of others. The test for determining compliance with 35 U.S.C. § 112, is whether the applicants have clearly defined their invention.
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. Tossing out the mere germ of an idea does not constitute enabling disclosure. Genentech Inc. v. Novo Nordisk 42 USPQ2d 1001.
As stated in the MPEP, 2164.08 ''[t]he Federal Circuit has repeatedly held that the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. ln re Wright, 999 F.2d 1557, 1561 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). Nevertheless, not everything necessary to practice the invention need be disclosed. In fact, what is well known is best omitted. In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991). AII that is necessary is that one skilled in the art be able to practice the claimed invention, given the Ievel of knowledge and skill in the art. Further the scope of enablement must only bear a reasonable correlation to the scope of the claims. See, e.g., In re Fisher, 427 F.2d 833, 839,166 USPQ 18, 24 (CCPA 1970). As concerns the breadth of a claim relevant to enablement, the only relevant concern should be whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate with the scope of protection sought by the claims. In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). See also Plant Genetic Sys., N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003) (alleged pioneer status of invention irrelevant to enablement determination.''
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-5, 8, 13-15, 18, 21 and 8-41 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lai et al., Nature Reviews. Lai teaches the compounds of Formula (IB) where the E3 ligase ligand is CRBN, VHL and MDM2, the target protein is ERRα, BRD4 and AR and the linker is -CH2-CH2-O-CH2-CH2-C(=O)-, -CH2-CH2-O-CH2-CH2-O-CH2-CH2-O-CH2-CH2- and -NH-C(=O)-CH2-O-CH2-CH2-O-CH2-CH2-O-CH2-CH2-NH-C(=O)-CH2-, etc. as set forth in Figure 2.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDA L COLEMAN whose telephone number is (571)272-0665. The examiner can normally be reached Mon-Fri 10-6 (flex).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey H. Murray can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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