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 .
DETAILED ACTION
Claims 1-12 are pending and examined on the merits herein.
Priority
This application claims the following priority:
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Claim Rejections - 35 USC § 112(b)
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 11 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.
-In claim 11, the phrase “A method for preparing a drug for targeted protein degradation, comprising preparing the drug for targeted protein degradation from the compound of claim 1,” renders the claim indefinite. It is not clear if the method is directed toward a method of preparing a compound of claim 1 or if the method is directed toward the preparation of a targeted protein degradation drug that involves the alteration of the compound of claim 1.
In view of compact prosecution, for the purpose of applying prior art, claim 11 is interpreted as a method for preparing a drug for targeted protein degradation comprising preparing a compound of claim 1.
Claim Rejections - 35 USC § 112(a)-Scope of Enablement
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 9-10 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 a method of inhibiting cereblon E3 ubiquitin ligase (CRBN) by administering a compound of instant formula (I), wherein = =O is =O, A is a 5-membered heteroaryl or a fused heteroaryl comprised of a phenyl ring and a 5-membered heteroaryl, and RA1 is H, does not reasonably provide enablement for a method for treating any disease associated with abnormal cell proliferation or a method of treating any cancer by administering any compound of instant 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 use the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
Claims 9 and 10 encompasses a method for treating any disease associated with any abnormal cell proliferation or any cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of any compound of instant formula (I):
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.
Thus, the breadth of the claim is great.
Level of Skill in Art
The level of skill in the art is a scientist with a PhD or a clinician.
State of the Prior Art
The prior art is silent regarding the use of the instantly claimed compounds.
WO 2019/204354 (PTO-892) teaches structurally and functionally similar compounds to those of instant formula (I), such as
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. ‘354 teaches its compounds as modulating the function or activity of the cereblon-containing E3 Ubiquitin Ligase Protein complex (pg. 4, lines 9-22; pg. 231). While ‘354 provides data on these compounds and their affinities for cereblon (see Table 11A beginning on pg. 231), ‘354 provides no data on administering its compounds to treat any type of disease.
Regarding small-molecule compounds that target ubiquitin ligase cereblon, Ito (Exploiting ubiquitin ligase cereblon as a target for small-molecule compounds in medicine and chemical biology, published 2021, PTO-892) teaches such compounds as promising and as being actively investigated (target). Ito teaches thalidomide and its derivatives as targeting CRBN (pg. 989), and specifically teaches lenalidomide and pomalidomide as derivatives that have excellent antimyeloma activity, and further teaches lenalidomide as additionally useful for the treatment of multiple myeloma, myelodysplastic syndrome, mantle cell lymphoma, and follicular lymphoma, and further teaches pomalidomide as additionally useful for myeloma patients who are resistant to lenalidomide (pg. 989). Ito teaches that while lenalidomide is a casein kinase 1 alpha (CSNK1A1) and specific neosubstrate of CRL4CRBN, thalidomide and pomalidomide do not induce degradation of CK1alpha (pg. 990, Col. 1).
Ito teaches that while the understanding of CRBN (cereblon) has progressed considerably over the last decade, CRBN is still an enigmatic protein and not much is known about its physiological roles. Ito further teaches that additional investigation is necessary (pgs. 995-996).
Thus, while the art teaches CRBN ligands as known and effective to modulate the activity of CRBN, the art teaches that structurally similar ligands, such as thalidomide, lenalidomide and pomalidomide (see Fig. 2 on pg. 989) treat distinct diseases, and further teaches that additional investigation is necessary.
Predictability in the Art
As can be seen by Table 11A starting on pg. 231 of WO2019/204354, structurally similar compounds that share a common core exhibit vastly different affinities to the cereblon protein, ranging from >.001 to 0.369.
As taught by Ito, while the understanding of CRBN has progressed considerably over the last decade, CRBN is still an enigmatic protein and not much is known about the detail of the physiological roles of it.
Thus, the art of cereblon ligands is unpredictable.
Working Examples
The instant specification provides zero working examples of a method of treating a disease. The instant specification merely provides IC50 values of species of compounds that inhibit CRBN/DDB1 protein (see [0128]-[0140] of the instant specification), wherein the exemplified compounds, A1-A20 all depict a =O at = =O of instant formula (I), and depict A as a 5-membered heteroaryl or a fused heteroaryl comprised of a phenyl ring and a 5-membered heteroaryl, R2 as mostly -C(O)-N(CH3)2, CH2N(CH3)2, or H, and RA1 as H.
The instant specification provides no correlation between the IC50 inhibitory values and methods of treating any disease, and the scope of the exemplified compounds is limited in comparison to the scope of the compound of instant formula (I).
Direction and Guidance
In view of the teachings of the prior art, the unpredictability of the art, the lack of working examples, and the breadth of the instant claims, the instant specification does not provide sufficient direction or guidance to use the invention commensurate in scope with these claims.
Quantity of Experimentation
The amount of experimentation required to determine which diseases are treated by which compounds of instant formula (I) would be astronomical, requiring proof-of-concept, and proceeding through all levels of lead identification and optimization. This amounts to invention, not development; it is an undue amount of experimentation.
Claim Rejections - 35 USC § 102
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 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 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.
Claims 1-5 and 11-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Registry No. 2637063-69-3 (STN Fil Registry, published 2021, PTO-892).
Regarding claims 1-5 and 11-12, RN 2637063-69-3 teaches:
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, which meets the limitations of instant formula (I) when:
A is a 5-membered heterocycloalkyl substituted;
RA4 is H
R2 is =O.
Regarding claim 11, since the method of preparing the compound merely requires that it be prepared, the compound of RN 2637063-69-3 meets this limitation since it is prepared as a compound (see the above 112(b) rejection for an interpretation of claim 11).
Regarding claim 12, the phrase “for targeted protein degradation” occurs in the preamble of the claim. When reading the preamble in the context of the entire claim, the recitation “for targeted protein degradation” is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02.
Registry number 2637063-69-3 is available as prior art as of 04/23/2021, the date it was indexed into the CAplus database. Since this date represents the date that the compound entered the CAPlus database on STN, this represents the date that each compound was made accessible to the public.
Per MPEP 2128, an electronic publication, including an online database or Internet publication (e.g., discussion group, forum, digital video, or social media post), is considered to be a "printed publication" within the meaning of 35 U.S.C. 102(a)(1) and pre-AIA 35 U.S.C. 102(a) and (b) provided the publication was accessible to persons concerned with the art to which the document relates. See In re Wyer, 655 F.2d 221, 227, 210 USPQ 790, 795 (CCPA 1981). . . Electronic publications on the internet or on an online database are considered to be publicly available as of the date the item was publicly posted.”
As such, the instantly claimed compound is anticipated.
Free of the Prior Art
Claims 6-8 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The closest prior art is Registry No. 2637063-69-3 (STN Fil Registry, published 2021, PTO-892), which teaches:
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, which meets the limitations of instant formula (I) when:
A is a 5-membered heterocycloalkyl substituted;
RA4 is H
R2 is =O.
However, RN 2637063-69-3 does not teach R2 as other than =O, and does not teach the species of instant claim 8.
Additionally close prior art is WO2023/125476 to Li (published 07/06/2023, by another, see additional inventors “Tu, Kaixin,” “Wang, Wei,” and “Chen, Qiuxia”, PTO-892), which teaches:
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(pg. 8, Original), which meets the limitations of instant formula (I) when A is 5, 9, or 10 membered ring and when R2 is C(O)NR21R22, wherein R21 and R22 are both a C1 alkyl, or R21 is H and R22 is a C1 alkyl; or R2 is C(O)R21, wherein R21 is a 6-membered heterocycloalkyl substituted by one R26, wherein R26 is a C1alkyl.
However, Li does not teach a pyrrolidine ring or an “H” or “=O” at the instant = =O position:
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, which are distinct features of the instantly claimed compound.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Primary Examiner, Art Unit 1622
