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 .
Status of the Claims
Claims 1, 3-5, 7, 31, 33, 45, 48, 49, 77, 247-252, 254, 255, 272, 273, 279-282, and 316-318 are pending. Claims 249-252, 254-255, 272-273, 279-280, 282 and 316 are withdrawn as being directed to a nonelected invention. Acknowledgment is made of the amendment to claims 1, 3-5, 7, 31, 33, 45, 48, 49, 77, 247, 249, 250, 252, 254, 279, and 318, and the cancellation of claims 6, 275, 277, and 278 in the reply filed 02/04/2026.
Restriction/Election Requirement
Applicant elected, without traverse, Group I, drawn to compounds of formula (I), in the reply filed on 07/28/2025.
Applicant further elected compound 30, shown below.
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Applicant’s elected species, compound 30, appears allowable. Therefore, according to MPEP 803.02: should the elected species be found allowable, the examination of the Markush-type claim will be extended. Examination has been extended to include the full scope of Group I, which are claims 1, 3-5, 7, 31, 33, 45, 48, 49, 77, 247, 248, 281, 317, and 318.
Claims 249-252, 254-255, 272-273, 279-280, 282 and 316 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 07/28/2025.
Withdrawn Objections/Rejections
Applicant’s amendment to the claims, filed -------02/04/2026, overcomes the objection to claims 3, 4, 31, 33, 48, 49, and 247 for minor informalities. The objection to claims 3, 4, 31, 33, 48, 49, and 247 has been withdrawn.
Applicant’s amendment to the claims, filed 02/04/2026, overcomes the rejection of claims 3, 6, and 318 under 35 U.S.C. 112(b) for indefiniteness. The rejection of claims 3, 6, and 318 has been withdrawn.
Applicant’s amendment to the claims, filed 02/04/2026, overcomes the rejection of claims 4 and 247 under 35 U.S.C. 112(d) for failing to include all the limitations of the claim upon which it depends. The rejection of claims 4 and 247 has been withdrawn.
Applicant’s amendment to the claims, filed 02/04/2026, overcomes the rejection of claims 1, 3-6, 31, 33, 48, 49, and 281 under 35 U.S.C. 102(a)(2) as being unpatentable over Wang et al. (WO 2021219070 A1). The rejection of claims 1, 3-6, 31, 33, 48, 49, and 281 has been withdrawn.
Applicant’s amendment to the claims, filed 02/04/2026, overcomes the rejection of claims 1, 3-6, 31, 33, 48, 49, and 281 under 35 U.S.C. 102(a)(2) as being unpatentable over Lei et al. (WO 2022068849 A1). The rejection of claims 1, 3-6, 31, 33, 48, 49, and 281 has been withdrawn.
Applicant’s amendment to the claims, filed 02/04/2026, overcomes the rejection of claims 1, 3-6, 31, 33, 48, 49, and 281 under 35 U.S.C. 102(a)(2) as being unpatentable over Lei et al. (WO 2022012622 A1). The rejection of claims 1, 3-6, 31, 33, 48, 49, and 281 has been withdrawn.
Applicant’s statement in accordance with 35 U.S.C. 102(b)(2)(C), filed 02/04/2026, overcomes the rejection of claims 1, 3-6, 31, 33, 48, 49, and 281 under 35 U.S.C. 102(a)(2) as being unpatentable over Sands et al. (WO 2021113557 A1). The rejection of claims 1, 3-6, 31, 33, 48, 49, and 281 has been withdrawn.
Maintained/Modified Rejections
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.
Claims 1, 4, 5, 31, 33, 45, 48, 49, 281, and 317 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 compounds of formula (I) where Y is as defined in claims 7 and 318, does not reasonably provide enablement for 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 the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention
The nature of the invention relates to compounds of formula (I) in claim 1. Such compounds are useful for degrading target proteins. This invention is also directed to compositions comprising said compounds.
Predictability of the art
The hypothetical compounds in claim 1 would be unpredictable in terms of one skilled in the art being able to synthesize every possible compound claimed in instant claim 1. 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 a 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.
Level of skill in the art
An ordinary artisan in the area of drug development would have experience in synthesizing and screening chemical compounds for particular activities, such as a medical doctor or chemist. Screening 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 often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
4. The breadth of the claims
The scope of the claims involves compounds of formula (I), shown below.
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Claim 1 is very broad in the number of variables and the options of substituents for each variable. Y is defined as a “target binding moiety”, and therefore has no limit to its structure. There is an infinite amount of hypothetical compounds included in claim 1.
5. The amount of direction provided, the presence or absence of working examples, and the quantity of experimentation necessary
The specification provides the synthesis of about 485 compounds . In all of the compounds synthesized, Y is as defined in claims 7 and 318.
Synthesis methods are not taught in the specification to provide for the aforementioned variable to include all of the possible substituents encompassed by the claims. Since the structure of Y is not defined by claim 1, there are an infinite number of compounds contained in formula (I). Y would not be expected to have any structural similarity, similar chemical properties, or similar utility.
Therefore, it would require one skilled in the art, such as a chemist, to perform an infinite number of reactions to determine which compounds of formula (I) can be prepared and would require synthesis methods other than those provided in the specification. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Applicant Argues:
Applicant states, in page 229 of the Remarks filed 02/04/2026, that one skilled in the art, such as an organic chemist, would be able to perform retrosynthetic analysis and classical synthesis in order to recognize the functional groups in a molecule and disconnect them, and perform methods to make such compounds. Applicant points to specific compounds and methods provided in the specification as examples for their scope. Examiner Responds:
Examiner agrees that one skilled in the art would be able to determine synthesis methods in most cases when the structure of a compound is defined, as discussed in Applicant’s Remarks. However, no structure is provided for the “target binding moiety” in the above rejected claims. Therefore, there is no starting point at which one skilled in the art could perform retrosynthetic analysis and determine synthesis methods to make such compounds. It is required for enablement that any skilled person in the art would be able to use the invention commensurate in scope with the claims. The target binding moieties (Y), all of which are not taught in the specification, do not have similar properties (e.g. stability, polarity, ADME/PK/PD properties, etc.), and therefore are not considered to have the same utility (e.g. efficacy, selectivity, toxicity, etc.) or to be obvious variants of one another. The different utilities and properties of the target binding moieties, the myriad target binding moieties encompassed by the claims, and the lack of examples provided by Applicant commensurate in scope with the myriad target binding moieties, results in an infinite breadth of the claims and undue experimentation on one skilled in the art to make the full scope of the instant 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.
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.
Claims 1, 4, 5, 31, 33, 45, 48, 49, 281, and 317 are 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.
Claims 1 recites that “Y is a target binding moiety”. The inventor or joint inventor should note that claim 1 is a reach-through claim. The claim attempts to obtain protection for subject matter that is prophetic and/or has yet to be invented, including any linker or target binding moiety that has not yet been invented. Similarly, the metes and bounds of a “target binding moiety” are not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification, in paragraphs [00142]-[00189] teach numerous, nonlimiting embodiments of target binding moieties. However, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments, of target binding moieties. Consequently, the compound of formula (I) comprising a “target binding moiety” has been rendered indefinite by the use of the reach-through protocol.
Claims 4, 5, 31, 33, 45, 48, 49, 281, and 317 are rejected as being dependent upon claim 1 and failing to give structure to Y.
Applicant Argues:
Applicant states, on page 232 of the Remarks filed 02/04/2026, that Y is “broadly applicable to degraders”. Applicant states that the target binding moiety is “well defined in the application”, and that the working examples demonstrate the diversity of Y groups.
Examiner Responds
Applicant stated that the target binging moiety is “well defined” in specification. However, open and non-limiting language is used in their example from paragraph [0431] where it states that “the target protein can be selected from”. Additionally, the target protein does not give structure to Y, but rather to what Y is binding to. The description “target binding moiety” in the claims does not include what the target actually is (e.g. is the compound selective for the protein and if so by how much, is the targeting active or passive, etc.), how the proteins is targeted (e.g. by the thought of the administrator, by chemical design, randomly as an assay, etc.), what the actual nature of the protein is (differing proteins would likely require differing targeting parameters, which is not given), how it is bound (e.g. competitively, non-competitively, covalently, etc.), how strongly it is bound (e.g. very strongly and/or covalently, very weakly and transiently, etc.), etc. Because the target binding moiety Y is described in such a way, either indefinitely or by undefined functional language, a reasonable interpretation of binding encompasses virtually any interaction, and thus virtually every small molecule that is known known, or yet to be created, fits the requirement. Because of the lack of possible understanding of the claimed elements and what they encompass, the metes and bounds of the claim is unclear.
The inventor or joint inventor should note that claims 5 and 317 are reach-through claims. The claim attempts to obtain protection for subject matter that is prophetic and/or has yet to be invented, which would include any target binding moiety that has not yet been invented which binds the target proteins listed in claims 5 and 317. Similarly, the metes and bounds of the target binding moieties which target “Bruton’s tyrosine kinase (BTK); tyrosine-protein kinase (TB/TSK)}; bromodomain-containing protein 4 (BRD4); FMS-like tyrosine kinase 3 (FLT-3); Brg/Brahma-associated factors (BAF complex); induced myeloid leukemia cell differentiation protein (MCL-1); signal transducer and activator of transcription 3 (STAT3); barrier-to-autointegration factor (BAF); and BCR-ABL to bring it into close proximity to E3 ligase to effect the protein’s ubiquitination and degradation” or “FLT3, SHP-2, GLD06, CDK4/6, MALTI1, BRAF, BCR-ABL, MEK, FGFR1 and FGFR3 and fusions thereof, RET and fusions thereof, BCL-2, PI3K Delta, MLL, Aurora A, KRAS, KRAS G12D, KRAS G12C, MDM2, MCL-1, PI3K alpha, elF4e, KSR, and TRIM24” are not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. Neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments of target binding moieties. Consequently, the compound comprising a target binding moiety which targets “Bruton’s tyrosine kinase (BTK); tyrosine-protein kinase (TB/TSK)}; bromodomain-containing protein 4 (BRD4); FMS-like tyrosine kinase 3 (FLT-3); Brg/Brahma-associated factors (BAF complex); induced myeloid leukemia cell differentiation protein (MCL-1); signal transducer and activator of transcription 3 (STAT3); barrier-to-autointegration factor (BAF); and BCR-ABL to bring it into close proximity to E3 ligase to effect the protein’s ubiquitination and degradation” or “FLT3, SHP-2, GLD06, CDK4/6, MALTI1, BRAF, BCR-ABL, MEK, FGFR1 and FGFR3 and fusions thereof, RET and fusions thereof, BCL-2, PI3K Delta, MLL, Aurora A, KRAS, KRAS G12D, KRAS G12C, MDM2, MCL-1, PI3K alpha, elF4e, KSR, and TRIM24” has been rendered indefinite by the use of the reach-through protocol.
Applicant Argues:
Applicant states, in page 233 of the Remarks filed 02/04/2026, that “taken as a whole, the compound of Formula (I) is well defined … with target degrader Y groups defined in the application”.
Examiner Responds
As discussed above, there are an indefinite number of compounds encompassed by Formula (I) in claims 5 and 317 since Y is not defined structurally. The instant claims do not describe the nature of the target binding moiety, except in terms of undefined functional language that is, itself, not properly defined in the instant specification. The instantly claimed compound is presented in such a vague fashion that the skilled artisan would not have any method of properly determining the metes and bound of the compound, and thus the metes and bounds of the claim as a whole is unclear.
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-5, 7, 31, 33, 48, 49, 77, 247, 248, 281, and 317 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 10, 11, 19, 24, 28, 32, 33, 49, 50, and 61 of copending Application No. 18/289,513 (hereinafter referred to as application ‘513). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims contain an overlapping genus of compounds with that of reference application ‘513. It has been held that a prior art disclosed genus of useful compounds is sufficient to render prima facie obvious a species falling within a genus. In re Susi, 440 F.2d 442, 169 USPQ 423, 425 (CCPA 1971), followed by the Federal Circuit in Merck & Co. v. Biocraft Laboratories, 847 F.2d 804, 10 USPQ 2d 1843, 1846 (Fed. Cir. 1989).
Reference application ‘513 teaches, in claim 61, compounds 218 and 219, which are the same as compound 38 of instant claim 247. Compound 47 of reference claim 61 is the same compound as in instant claim 248. Application ‘513 teaches, in claim 61, compounds which read on the instant claims. For example, compounds 23, 115, 185-187, and 214 shown below. These compounds read directly on instant claims 1, 3-5, 7, 31, 33, 48, 49, 77, and 317.
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Reference application ‘513 teaches a pharmaceutical composition comprising said compounds, which reads on instant claim 281.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant Argues:
Applicant states, on page 241 of the Remarks filed 02/04/2026, that the compounds of the copending application are different than those of the instant invention.
Examiner Responds:
It has been shown above that the compounds read directly on the instant invention.
New Objections
Necessitated by Claim Amendment
Claims 77 and 247 are objected to because of the following informalities:
Rule 1.141(a) states:
Two or more independent and distinct inventions may not be claimed in one national application, except that more than one species of an invention, not to exceed a reasonable number, may be specifically claimed in different claims in one national application, provided the application also includes an allowable claim generic to all the claimed species and all the claims to species in excess of one are written in dependent form (§ 1.75) or otherwise include all the limitations of the generic claim.
Claims 77 and 247 claim a large number of species of the generic claim, but in independent format. Multiple inventions may not be claimed in a single application unless they are species claims which are dependent upon the larger, generic claim. In the past, the Office has held a “reasonable number” to be five (5) species. The present claim contains well over this number of species. One could envision forty pages of species compounds in a single claim which is not dependent upon any genus claim. This would cause undue burden to the Office in examining such a large claim. Therefore, it is recommended that claims 77 and 247 either be dependent from a larger, genus claim, or, that claims 77 and 247 incorporate all of the limitations of the genus claim.
Appropriate correction is required.
New Rejections
Necessitated by Claim Amendment
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 77 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.
Claim 77 recites the limitations “W”, “L”, “A1”, “A2”, “A3”. There is insufficient antecedent basis for these limitations in the claim.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 248 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 248, which is dependent upon claim 1, teaches compound 26, where the pyridinyl group is para-substituted. However, newly amended claim 1 teaches that the pyridinyl group may only be meta- substituted. Therefore, claim 248 fails to include the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 5, 49, and 281 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2021180103 A1), with an effective filing date of 11 March 2020.
Wang et al. teaches compounds for the degradation of Bruton’s tyrosine kinase (BTK) by conjugation of BTK inhibitors (target binding moieties) with E3 ligase ligand moieties (Degrons), attached by a linker. The target binding moieties are defined by formula (I), shown below.
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The compounds from paragraphs [0924], [0764], and [0615] are shown below.
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It can be seen in the compounds above that the target binding moiety on the left follows formula (I) above, the Linkers are alkyl or haloalkyl, and the Degrons are
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, as shown in reference claim 7. A pharmaceutical composition comprising said compounds is taught in claim 40.
These compounds differ from the instant compounds in that the pyridine on the Degron is para-substituted rather than meta-substituted. Therefore, these compounds are position isomers of the compounds of instant claims 1, 4, 5, 49, and 281. MPEP 2144.09 II states: “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). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.).”
Therefore, since the prior art compounds are positional isomers of the instant compounds, that the instant compounds are rendered prima facie obvious by the prior art compounds. One would expect the compounds to have the same utility and properties.
Claims 1, 4, 5, 31, 33, 48, 49, 281, 317, and 318 are rejected under 35 U.S.C. 103 as being unpatentable over Hornberger et al. (WO 2022047145 A1), with an effective filing date of 28 August 2020.
Hornberger et al. teaches in claim 1 a hetero-bifunctional compounds having the chemical structure PTM-L-CLM, wherein L is the linker, PTM is the targeting moiety represented by the structure:
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223
391
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and CLM is an E3 ubiquitin ligase binding moiety represented by the structure:
PNG
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124
220
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One specific compound taught, in claim 3, is shown below.
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138
603
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In this compound, the Linker is
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101
286
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, and the CLM and PTM structures are shown above and in claim 1. A pharmaceutical composition comprising said compound is taught in claim 26. The degradation of BRaf is taught by using this method in paragraph [00307].
These compounds differ from the instant compounds in that the pyridine on the CLM is para-substituted rather than meta-substituted. Therefore, these compounds are constitutional isomers of the compounds of instant claims 1, 4, 5, 31, 33, 48, 49, 281, 317, and 318. MPEP 2144.09 II states: “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). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.).”
Therefore, since the prior art compounds are positional isomers of the instant compounds, that the instant compounds are rendered prima facie obvious by the prior art compounds. One would expect the compounds to have the same utility and properties.
Conclusion
Claims 1, 3-5, 7, 31, 33, 45, 48, 49, 77, 247, 248, 281, 317, and 318 are rejected.
THIS ACTION IS MADE FINAL. 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.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624