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 .
Priority
The instant application, filed 05/03/2022, is a 371 filing of PCT/US2020/059082, filed 11/05/2020, which claims domestic priority to U.S. provisional application number 62/931,541, filed 11/06/2019.
Amendments and Claim Status
The following amendment filed on 10/28/2025 is acknowledged and entered.
Claims 1, 2, 4, 6, and 8 are amended;
Claims 13, 15, 17 are cancelled;
Claims 19 and 20 are added;
Claims 2, 3, 12, 14, 16, and 18 remain withdrawn according to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species;
Claims 1-12,14,16 and 18-20 are pending.
Claims 1, 4-11, 19 and 20 are currently under prosecution.
Information Disclosure Statement
The Information Disclosure Statement filed on 10/28/2025 is acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statement is considered.
Response to arguments
Applicant’s arguments filed 10/28/2025 with respect to the claim objections and claim rejections under 35 U.S.C. §§ 112(a), 112 (b), and 103 have been fully considered.
With respect to the objection to claim 1, the removal of the trailing parentheses from claim 1 is sufficient to overcome the rejection.
With respect to the rejection of claims 1, 4-9, and 11 under U.S.C. § 112(a), Applicant’s arguments have been fully considered but are not persuasive for the reasons set forth below. The arguments made by Applicant are herein addressed as follows.
The following section of the MPEP is relied upon for response to Applicant’s arguments. According to MPEP § 2163.02, the standard for determining compliance with the written description requirement is as follows,
Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"
Applicant asserts that the amendment of the linker recitation within the claims there is an even tighter nexus with the teachings and examples disclosed in the specification. Applicant further argues that a person skilled in the art will readily understand the compounds comprised of degrons D1a to D1d will reliably bind cereblon and work in a similar manner. Applicant relies on MPEP § 2163 (misprinted in the remarks as MPEP § 2316) and cites case law for the proposition that a single species is an adequate description of the claimed genus.
Applicant’s argument is found unpersuasive, because written description requires possession, not merely feasibility or similarity. While the level of skill in the art is relevant, it cannot substitute for written description to demonstrate possession of the claimed compounds. The written description requirement is satisfied only when the specification reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date. General statements of feasibility or references to what could be made by a skilled artisan, and expected similar function do not establish or equate to possession. The amendments to the claims are insufficient to overcome the rejection, as Applicant still presently claims more than is actually possessed, as evidenced by the instant specification.
Genentech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent 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”.
For the reasons set forth above, Applicant’s arguments do not overcome lack of written description set forth in the rejection. Applicant has presented no additional data or results to demonstrate that applicant was in possession of the compounds as claimed.
Accordingly, the rejection under 35 U.S.C. § 112 (a) over inadequate written description is hereby maintained.
With respect to the rejection of claim 6 under U.S.C. § 112(b), the amendment of the integer values of n are sufficient to overcome the rejection.
With respect to the rejection of claims 1 and 4-11 under 35 U.S.C. § 103 as being unpatentable over Crew et al. (US 20160058872 A1, published March 3, 2016), hereinafter Crew, in view of Remiszewski et al. (J. Med. Chem. Vol 46, pg. 4609-4624, published September 13, 2003), hereinafter Remiszewski, and Zhang (Clin Cancer Res, Vol 24, Issue 16, pg. 3941-395, published May 15, 2018), hereinafter Zhang, Applicant’s arguments have been fully considered but are not persuasive for the reasons set forth below. The arguments made by Applicant are herein addressed as follows.
Applicant argues that the Examiner’s statement that bromodomain proteins and HDACs are “substitutable equivalents” reflects a misunderstanding of cancer biology and oversimplifies the complexity of cancer.
Applicant’s argument is not persuasive. The office has not asserted that bromodomain proteins and HDACs are biologically identical, but rather that they are art-recognized, functionally-related cancer targets within chromatin regulatory networks, as explicitly taught by Zhang. Zhang demonstrates that bromodomain function and HDAC activity are closely intertwined in regulating gene expression and tumor cell fate. As such, Zhang provides a clear therapeutic motivation to target either protein class for cancer intervention. Under MPEP § 2144.06, art-recognized equivalents used for the same purpose may be substituted without negating obviousness. Accordingly, the substitution of an HDAC-targeting moiety for a bromodomain-targeting moiety in a bifunctional degrader framework directed to cancer therapy would have been obvious to a person of ordinary skill in the art.
Applicant contends that Crew fails as a primary reference, because it does not disclose selective degradation of HDAC6/8, nor does it identify a bifunctional compound containing a HDAC6/8-targeting ligand.
Applicant’s argument is found unpersuasive because the argument mischaracterizes the role of Crew in the rejection. Crew is not relied upon for teaching HDAC6/8 degradation, but rather for teaching the general bifunctional degrader architecture, including a PTM-L-CLM framework, PEG linkers, and cereblon binding moieties such as pomalidomide. The office explicitly relies on Remiszewski to supply the specific HDAC-targeting ligand and on Zhang to provide motivation to substitute that ligand into the scaffold taught by Crew. The reference need not teach the identical biological target to be properly combined under 35 U.S.C. § 103. The rejection is therefore based on the teachings of the references in combination, and not on Crew alone.
Applicant further argues that Crew’s compound 22 shows degradation of ERRa rather than BRD4, and therefore it would not have been selected as a lead compound for HDAC6/8 degraders—citing lead compound case law (Takeda, Otsuka) for support of the argument.
Applicant’s reliance on lead compound precedent is misplaced. The instant rejection does not depend on identifying a “lead compound” in the sense required for a pharmaceutical optimization cases. Rather, the rejection is based on rational substitution of known functional elements within a known bifunctional degrader framework, as permitted under KSR and MPEP § 2143. The office has not relied on structural similarity alone, but express teachings of (i) bifunctional degrader design taught by Crew; (iI) HDAC-targeting ligands taught by Remiszewski; and (iii) motivation to target HDACs in cancer and chromatin regulation taught by Zhang. Accordingly, the rejection does not rely on impermissible hindsight, or improper lead compound selection analysis.
Applicant asserts that Remiszewski merely teaches small molecule HDAC inhibitors, and does not suggest an incorporation into bifunctional degraders—emphasizing differences between inhibition and degradation mechanisms. Applicant further argues that Remiszewski does not suggest that the disclosed small molecule inhibitor would be effective if integrated into a different type of chemical entity. Applicant further contends that the targeting ligand is not relied upon for its ability to directly inhibit the activity of the target, but rather to bind it so that it target the selected protein for degradation.
Applicant’s argument is not persuasive because Remiszewski is relied upon for teaching HDAC-binding ligands, not for teaching degrader activity. Crew explicitly teaches that a wide variety of protein targeting ligands may be incorporated into bifunctional degrader compounds, provided that they bind the protein of interest (paragraph [0052]). The art does not require that a ligand be previously used in a degrader to render its use obvious. As recognized in PROTAC design principles taught by Crew, the protein-binding function is the relevant criterion to the PTM moiety. Substituting a known HDAC-binding moiety into a known degrader scaffold would have been within the routine skill of the art, specifically outlined by the teachings of Crew (paragraph [0051]).
Applicant cites review articles and experimental failures to argue that the PROTAC field is unpredictable, and that a person of ordinary skill would not have had a reasonable expectation of success in achieving HDAC6/8 degradation.
While the art acknowledges that degrader optimization can be complex, predictability alone does not negate the obviousness where there is a reasonable expectation of success. Crew explicitly and expressly teaches successful degradation using cereblon-based degraders with PEG linkers and diverse protein-targeting ligands. Zhang provides motivation to pursue HDAC targets due to their role in chromatin regulation and cancer. The examiner has not asserted any certainty of success, but rather a reasonable expectation that substituting a known HDAC-binding ligand into a known degrader framework would yield a functional degrader compound.
Applicant points to experimental data in the specification demonstrating successful HDAC6/8 degradation, and argues that this evidence overcomes the prima facie case of obviousness.
The data cited by applicant demonstrates that the claimed compounds function as intended. However, evidence that a compound works does not, by itself, establish nonobviousness. Applicant has not shown that the results are unexpected relative to the closest prior art or that they represent a surprising improvement over what would have been reasonably expected based on the combination of teachings of Crew, Remiszewski, and Zhang. Moreover, the claims are not commensurate in scope with the asserted results, as the claims encompass a broad genus of compounds beyond those specifically tested. Accordingly, the evidence is insufficient to overcome the prima facie case of obviousness.
Thus, all arguments presented by Applicants have been addressed and are found unpersuasive for the reasons presented herein and in the previous non-final rejection. Applicants are reminded that “attorney argument [is] not the kind of factual evidence that is required to rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Mere attorney argument or conclusory statements without adequate supporting evidence are insufficient to rebut a prima facie case of obviousness.
Regarding new claims 19 and 20, the combination of references continues to meet the claim limitations wherein the pomalidomide moiety of the compounds taught by Crew renders obvious structure (D1a) wherein X1 is C(O) and X2 is NH. As such, the previous rejection is amended to include these new claims.
The reasons set forth above, Applicant’s arguments do not overcome the prima facie case of obviousness established in the rejection. The combination of Crew, Remiszewski, and Zhang continues to teach or suggest each limitation of claims 1 and 4-11, and provides both motivation and a reasonable expectation of success.
Accordingly, the rejection under 35 U.S.C. § 103 is maintained.
Claim Rejections - 35 U.S.C. § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 4-9 and 11 are rejected under 35 U.S.C. § 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. § 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 4-9 and 11 of the instant application are drawn to compounds having following substituents:
Degron is
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X1 is CH2 or C(O)
X2 is CH2, NH, or O
n is 1-6
The compound of claim 7 represented by
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35 U.S.C. § 112(a) and the first paragraph of pre-AIA 35 U.S.C. § 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc); Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111,1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim’s enablement is not equally conclusive of that claim’s satisfactory written description"). The written description requirement has several policy objectives. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert, denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaffv. Wells Bees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); EliLilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm.,927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). An application specification may show actual reduction to practice by describing testing of the claimed invention.
In the present case, the important factors leading to a conclusion of inadequate written description is the absence of any working example of the invention as claimed, and the lack of predictability in the art.
In the instant specification, there is no disclosure of compounds having the following claimed substituents:
Degron as
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X1 as CH2
X2 as CH2 or O
n as 6
The compound of claim 7 represented by
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The instant specification (pages 39-46) teaches compounds which are characterized as having only the following substituents:
Degron is
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X1 is C(O)
X2 is NH
n is 1-5
The compound of claim 7 is
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Therefore, the compounds described in the instant specification detail only a limited number of the total substituents claimed (see substituents 1-5, above). All working examples presented in the instant specification are related to the compounds containing only a fraction of the total claimed substituents (see substituents 11-15, above).
There are no working examples in the instant specification for the wide range of substituents claimed, but for which evidence of possession has not been provided (see substituents 6-10, above). Thus the instant specification does not provide any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application.
Vas-Cath Inc. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F. 3d 1565, 1572, 41 USPQ2d 1961, 1966(1997); In re Gosteli, 872 F.2d 1008, 1012,10 USPQ2d 1614, 1618 (Fed Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.") Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim. See, e.g., Fiers v. Revel, 984 F.2d at 1169, 25 USPQ2d at 1605; Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021.
Thus, since Applicant has not described in adequate detail methods to synthesize compounds containing the claimed substituents, or provided evidence that said compounds have been characterized, or that they exist, an ordinary skilled artisan could not completely envisage Applicants’ invention. Moreover, it is clear that the written description requirement has not been met since Applicant has not provided any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application. Thus, claims 1, 4-9 and 11 of the instant application are not supported by the instant specification and thus a rejection under 35 U.S.C. § 112 (a) for failing to comply with the written description requirement is proper.
Claim Rejections - 35 U.S.C. § 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.
Claims 1, 4-11, 19 and 20 are rejected under 35 U.S.C. § 103 as being unpatentable over Crew, in view Remiszewski, and further in view of Zhang.
The instant claims are drawn to bifunctional molecular compositions that induce targeted protein degradation. The elected species is a bifunctional compound comprised of a moiety that targets histone deacetylases HDAC6/8 and a second moiety, pomalidomide, that binds the E3 ligase, joined by a covalent linker that covalently links these two binding elements. The recruitment and close proximity of E3 ligase induces the ubiquitination and the subsequent proteasomal degradation of HDAC6/8. The claims further encompass specific structural features of the HDAC6/8 and E3-ligase moieties, the chemical nature of the linker, and pharmaceutical compositions containing these bifunctional compounds.
Crew teaches the design and use of bifunctional compounds that act as targeted to craters by recruiting a target protein to E3 ubiquitin ligase for ubiquitination and subsequent proteasomal degradation. These bifunctional compounds have the chemical structure comprising the general formula PTM-L-CLM made up of (1) a protein target moiety that targets a protein of interest (PTM); 2) a linker group, such as polyethylene glycol (L), (page 20) ; and 3) a celebron E3 ubiquitin ligase binding moiety (CLM), such as pomalidomide (claim 1, claim 4). The result is a bifunctional compound used to degrade specific proteins (Figure 1). The disclosure further details a pharmaceutical composition comprising the compound of the general formula PTM-L-CLM (claim 12). The protein of interest targeted by the invention detailed by Crew is a bromodomain containing protein, of particular importance in cancer therapy (paragraphs [0008-0009]). Crew teaches in the area of compounds, but for the purposes of this rejection, the teachings will focus on molecule 22 (page 96), also known as CAS Registry Number: RN 1818885-36-7. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 1818885-36-7, Entered STN: 10 Nov 2015] (Figure 1 a).
Although two-thirds of the bifunctional chemical compound taught by Crew is identical to the elected species, the disclosure by Crew does not teach specifically targeting histone deacetylase protein with a bifunctional chemical composition.
However, the deficiencies of Crew are remedied by Remiszewski, who teaches N-Hydroxy-3-phenyl-2-propenamides as novel inhibitors of Humane Histone Deacetylase (Title), an important cancer target (page 4609). Specifically, Remiszewski teaches molecule 13g, also known as CAS Registry Number: RN 404951-53-7. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 404951-53-7. Entered STN: 10 Apr 2002] (page 4612), as shown in Figure 1b. The substitution of the propenamide moiety, known to target HDAC (Abstract), for the bromodomain moiety yields the elected species (Figure 1c).
Figure 1. Prior art combination to yield the instantly claimed elected species
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Figure 1 a) Crew RN 1818885-36-7 b) Remiszewski RN 404951-53-7 c) Substitution of Cancer protein targets to yield instantly claimed elected species.
Because both bromodomain containing proteins and histone deacetylases are cancer targets, they are considered substitutable equivalents used for the same purpose, i.e. treating cancer. According to MPEP § 2144.06 (II), art-recognized equivalents substituted for the same purpose are rendered obvious. The courts have stated:
In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) (The mere fact that components are claimed as members of a Markush group cannot be relied upon to establish the equivalency of these components. However, an applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. Of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. “This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor.” 209 USPQ at 759.). An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
As both the bromodomain targeting ligands and the histone deacetylase targeting ligands are designed as cancer targets, they are considered equivalents. Therefore, it would have been obvious to a person of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to substitute the functionally equivalent HDAC protein cancer target for the bromodomain containing protein target for the common purpose of treating cancer.
Explicit motivation to modify the protein targeting moiety of Crew using the histone deacetylase inhibitors taught by Remiszewski is provided by Zhang, who demonstrates that HDAC activity and bromodomain-containing protein function are closely intertwined within chromatin regulatory networks that control gene expression in tumor cell fate (page 3941-2). This establishes that HDAC proteins, such as HDAC6 and HDAC8 are highly desirable protein targets for therapeutic intervention, and that targeting these enzymes with a bifunctional degrader framework is scientifically and clinically justified. The teachings justify the linkage of HDAC and bromodomain protein-targeting motifs as therapeutic strategies, and demonstrates the interchangeability of targeting these proteins for anticancer effects The combined teachings provide both the molecular basis, and therapeutic incentive to substitute an HDAC targeting protein in the place of bromodomain containing protein to arrive at the instantly claimed species.
Regarding claim 1, Crew teaches the general formula PTM-L-CLM, wherein the linker is a polyethylene glycol moiety and CLM is pomalidomide, as that of the elected species. The substitution of N-Hydroxy-3-phenyl-2-propenamides as the HDAC protein targeting molecule renders the elected species obvious, according to the rationale outlined above.
Regarding claim 4, the linker taught by Crew is a polyethylene glycol linker.
Regarding claim 5, the polyethylene glycol linker comprises 2 PEG units.
Regarding claim 6, the species derived from the substitution outlined above renders obvious Formula (I-1) wherein n is 2, and Formula (I-2).
Regarding claim 7, the pomalidomide moiety of the compounds taught by Crew renders obvious structure (D1a) wherein X1 is C(O) and X2 is NH.
Regarding claim 8, the species derived from the substitution outlined above renders obvious Formula (I-5).
Regarding claim 9, the species derived from the substitution outlined above renders obvious Formula (I-9), wherein X is O and n is 2.
Regarding claim 10, the species derived from the substitution outlined above renders obvious structure (1), the elected species.
Regarding claim 11, Crew teaches a pharmaceutical composition comprising compounds of the general formula of PTM-L-CLM.
Regarding new claims 19 and 20, the pomalidomide moiety of the compounds taught by Crew renders obvious structure (D1a) wherein X1 is C(O) and X2 is NH.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623