DETAILED ACTION
Notice of Pre-AIA or AIA Status
The inventor or joint inventor should note that the instant invention, 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 1-4, 7-12 and 14-24 are pending in the instant invention. According to the Amendments to the Claims, filed June 10, 2026, claim 1 was amended and claims 5, 6 and 13 were cancelled.
Status of Priority
This invention is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/IL2021/051530, filed December 23, 2021, which claims priority under 35 U.S.C. § 119(a-d) to IL 279736, filed December 23, 2020 and under 35 U.S.C. § 119(e) to US Provisional Application Nos. a) 63/279,698, filed November 16, 2021; and b) 63/220,517, filed July 11, 2021.
Although the inventor’s or joint inventor’s claim for the benefit of a prior-filed invention under 35 U.S.C. § 119(e) is acknowledged, the inventor or joint inventor has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. § 119(e) as follows:
The later-filed invention must be an invention for a patent, for an invention which is also disclosed in the prior-filed inventions (the provisional inventions). The disclosure of the invention in the prior-filed inventions and in the later-filed invention must be sufficient to comply with the requirements of 35 U.S.C. § 112(a). {See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)}.
The specification of the prior-filed inventions, US Provisional Application Nos.: a) 63/279,698; and b) 63/220,517, respectively, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. § 112(a) for one or more claims of this invention for the following reason: the specification in the instant invention has been amended with respect to the scope of formula (I), which now discloses amended definitions for at least W and the proviso, respectively, and is no longer coextensive with that of US Provisional Application Nos.: a) 63/279,698; and b) 63/220,517, respectively.
Consequently, since the specifications of US Provisional Application Nos.: a) 63/279,698; and b) 63/220,517, respectively, lack adequate support or enablement for one or more claims of the elected invention of Group III, as defined below in Restrictions / Election of Species, and in the manner provided by 35 U.S.C. § 112(a), the first Office action on the merits of all relevant claims drawn to Group III will be prosecuted according to the earliest effective filing date afforded this invention, which is that of IL 279736, filed December 23, 2020.
Restrictions / Election of Species
PNG
media_image1.png
200
400
media_image1.png
Greyscale
The inventor’s or joint inventor’s provisional election of the following, without traverse, in the reply filed on June 10, 2026, is acknowledged: a) Group III - claims 1-4, 7-12 and 14-16; and b), - p. 23, compound 8a, shown to the right below, and hereafter referred to as 2-(((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-N-(4-(4-(4-(6-amino-5-(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-pyridin-3-yl)-1H-pyrazol-1-yl)piperidin-1-yl)-4-oxobutyl)acrylamide, where the combination of R = -the bioactive group, crizotinib; W = the linker, -NHCH2(CH2)n-, wherein n = 2; G = O; X = -a bond-; and R1 = -a releasing group comprising the protein binding ligand, Ibrutinib (Ibr). Claims 1, 7, 11 and 14-16 read on the elected species. Affirmation of this election must be made by the inventor or joint inventor in replying to this Office action.
PNG
media_image2.png
271
631
media_image2.png
Greyscale
Similarly, the inventor or joint inventor should further note that the requirement is still deemed proper and is therefore made FINAL.
Likewise, the inventor or joint inventor should further note that the elected species, shown to the right above, was found to be free of the prior art. Thus, the examiner has expanded the forthcoming prosecution to include all claims relevant to the genus of Group III, for a first Office action and prosecution on the merits.
Moreover, the inventor or joint inventor should further note that claims 3, 4, 8-10, 12 and 17-24 were withdrawn from further consideration, pursuant to 37 CFR 1.142(b), as being drawn to a nonelected or cancelled invention, there being no allowable generic or linking claim.
Thus, a first Office action and prosecution on the merits of claims 1, 2, 7, 11 and 14-16 is contained within.
Specification Objection - Disclosure
The inventor or joint inventor is advised to format the specification according to 37 CFR 1.77(c). Revisions should particularly address bold-type, underline, and/or upper case formatting. Appropriate correction may be required.
Specification Objection - Title
The inventor or joint inventor is reminded of the proper content of the title of the invention.
The title of the invention should be brief, but technically accurate and descriptive and should contain fewer than 500 characters. See 37 CFR 1.72(a) and MPEP § 606.
The title of the invention is not technically accurate and descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. In the revised title, the examiner suggests identifying: a) the substituted covalent ligand directed releasing (CoLDR) alkenes represented by the formula (I); and b) a particular utility for the substituted covalent ligand directed releasing (CoLDR) alkenes represented by the formula (I).
The following title is suggested: SUBSTITUTED METHACRYLAMIDE PROTEIN BINDERS AS COVALENT LIGAND DIRECTED RELEASING (CoLDR) COMPOUNDS.
Appropriate correction is required.
Specification Objection - Abstract
The inventor or joint inventor is reminded of the proper content of an abstract of the disclosure.
With regard particularly to chemical patents, for compounds or compositions, the general nature of the compound or composition should be given as well as the use thereof, e.g., The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics. Exemplification of a species could be illustrative of members of the class. For processes, the reactions, reagents and process conditions should be stated, generally illustrated by a single example, unless variations are necessary. See MPEP § 608.01(b), Section B.
The abstract of the disclosure is objected to because it fails to exemplify any members or formulae illustrative of its class. Correction is required. See MPEP § 608.01(b).
The examiner suggests incorporating the structure of formula (I) into the abstract, to overcome this objection.
Claim Objections
Claim 1 is objected to because of the following informalities: for clarity, precision, to avoid issues under 35 U.S.C. § 112(a) and/or 35 U.S.C. § 112(b) and to comply with the Requirement for Restriction / Election of Species, mailed on April 26, 2026, the existing recitation should be replaced with the following recitation:
A Covalent Ligand Directed Releasing (CoLDR) compound represented by the formula (I):
PNG
media_image3.png
200
400
media_image3.png
Greyscale
(I)
wherein:
R1 is a releasing group comprising the protein binding ligand, Ibr, of the following formula:
PNG
media_image4.png
365
186
media_image4.png
Greyscale
Ibr;
X is a bond;
G is O or S;
W is a linker selected from the group consisting of:
-NH-, -N(CH3)-, -NH(CH2)2NH-, -NH(CH2)3-, -NH(CH2)5-,
-NHCH2CH2(OCH2CH2)2-, -NHCH2CH2(OCH2CH2)4-, and -O(CH2)2NH-; and
R is a bioactive group selected from the group consisting of an approved drug, a targeted inhibitor, a cytotoxic, a chemotherapeutic, a radiopharmaceutical, and a substructure of any one of the following formulas (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l), (m), (n), (o), and (p):
(a) CH2C≡CH;
(b) CH2CH2C≡CH;
(c) 1,4-phenylene-C≡CH;
(d) 4-[NHC(O)(CH2)4C≡CH]-piperidin-1-yl;
(e) C(NH)NHC(O)OC(CH3)3 (Boc-guanidine);
(f) nile red, or a derivative thereof, of the following formula:
PNG
media_image5.png
170
243
media_image5.png
Greyscale
;
(g) dibenzyl cyclooctyne, or a derivative thereof, of the following formula:
PNG
media_image6.png
163
213
media_image6.png
Greyscale
;
(h) C(O)CH2CH2(OCH2CH2)5NHC(O)OC(CH3)3;
(i) boron dipyrromethene (BODIPY), or a derivative thereof, of the following formula:
PNG
media_image7.png
144
249
media_image7.png
Greyscale
;
(j) pomalidomide, or a derivative thereof, of the following formula:
PNG
media_image8.png
260
197
media_image8.png
Greyscale
;
(k) C(O)NH-afa (afatinib);
(l) C(O)-adamantan-1-yl;
(m) crizotinib, or a derivative thereof, of the following formula:
PNG
media_image9.png
197
349
media_image9.png
Greyscale
;
(n) C(O)-1,4-phenylene-C(O)H;
(o) fluorescein isothiocyanate (FITC), or a derivative thereof, of the following formula:
PNG
media_image10.png
186
196
media_image10.png
Greyscale
; and
(p) thalidomide, or a derivative thereof, of the following formula:
PNG
media_image11.png
243
165
media_image11.png
Greyscale
.
Appropriate correction is required. See MPEP § 2173.02.
Claim 2 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The CoLDR compound according to claim 1, wherein the compound is represented by formula (IA):
PNG
media_image12.png
200
400
media_image12.png
Greyscale
(IA).
Appropriate correction is required. See MPEP § 2173.02.
Claim 7 is objected to because of the following informalities: for clarity, the claim is dependent upon an objected base claim. Appropriate correction is required.
Claim 11 is objected to because of the following informalities: for clarity, the claim is dependent upon an objected base claim. Appropriate correction is required.
Claim 14 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The CoLDR compound according to claim 1, wherein upon interaction between a protein and the protein binding ligand, Ibr, the releasing compound, R1, is released.
Appropriate correction is required. See MPEP § 2173.02.
Claim 15 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The CoLDR compound according to claim 1, wherein a covalent bond is formed between a protein and the protein binding ligand, Ibr.
Appropriate correction is required. See MPEP § 2173.02.
Claim 16 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The CoLDR compound according to claim 15, wherein the covalent bond is formed via an NH2, OH, or SH moiety of the protein and the double bond of the C(CH2) of the compound represented by the formula (I).
Appropriate correction is required. See MPEP § 2173.02.
Allowable Subject Matter
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS M. WILLIS, whose telephone number is 571-270-5757. The examiner may normally be reached on Monday thru Thursday from 8:00-6:00 EST. The examiner is also available on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Jeffrey Murray, may be reached on 571-272-9023. The fax phone number for the organization where this invention or proceeding is assigned is 571-273-8300.
Information regarding the status of an invention may be obtained from Patent Center. For more information about Patent Center, see https://www.uspto.gov/patents/apply/patent-center. Should you have questions on access to Patent Center, contact the Patent Electronic Business Center (PEBC) at 866-217-9197 (toll-free) or ebc@uspto.gov.
/DOUGLAS M WILLIS/
Primary Examiner, Art Unit 1624
Prosecution Insights