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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US2021/029391 filed April 27, 2021, which claims the benefit of US Provisional Application No. 63/016,130 filed April 27, 2020. All claims have been given an effective filing date of April 27, 2020.
Election/Restriction
Applicant's election without traverse of Group I (Claims 1, 5, 23, 32-34, 54, 61, and 75) and species election of:
SEQ ID NO: 96
SEQ ID NO: 47
Means for preferentially binding HDMX over HDM2
in the reply filed on January 5, 2026 is acknowledged.
Claims 35, 37, 45, 50, 52-53, 69-74, and 78-79 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 5, 2026.
Claim Status
Claim listing filed on October 14, 2025 is pending. Claims 2-4, 6-22, 24-31, 36, 38-44, 46-49, 51, 55-60, 62-68, and 76-77 are canceled. Claims 23, 32, and 35 are amended. Claims 35, 37, 45, 50, 52-53, 69-74, and 78-79 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions or species. Claims 1, 5, 23, 32-34, 54, 61, and 75 are examined upon their merits.
Information Disclosure Statement
The information disclosure statements filed on 05/08/2023, 05/24/2024, 01/17/2025, and 01/05/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 1 and 54 are objected to because of the following informalities:
Claim 1(a) requires a semi-colon at the end to read “relative to the amino acid sequence of SEQ ID NO: 101;”
Claim 54 recites “structurally stabilized” in the first line and should be corrected to “structurally-stabilized” with a hyphen as is used in all other instances in the claims.
Claim 54 recites “G Lys” in the last line on page 7 wherein “Lys” with the “G” deleted is correct.
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Specifically, Claim 75 recites “a means for preferentially binding HDMX over HDM2” and is interpreted under 35 U.S.C. 112(f).
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.
Claims 1, 5, 23, 33-34, 54, 61, and 75 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, 5, 23, 33-34, 54, 61, and 75 are indefinite because they recite the abbreviations “HDMX” and “HDM2” without defining the abbreviations in the claims. For the purpose of compact prosecution, “HDMX” is interpreted as “human double minute x” and “HDM2” is interpreted as “human double minute 2.”
Claim 1 recites “a hydrophilic amino acid.” Claim 54 recites “a hydrophobic amino acid less hydrophobic than alanine” and “a hydrophilic amino acid.” The structural metes and bounds of what is encompassed by “a hydrophilic amino acid” and “a hydrophobic amino acid” are unclear. As evidenced by Millipore Sigma Amino acids Reference Chart (2026), hydrophobicity is dependent on the pH of the solution. For example, Asp is considered hydrophilic at pH 7 and is considered neutral at pH 2 (bottom table). The specification lists “non-limiting examples of hydrophobic amino acids” and “non-limiting examples of hydrophilic amino acids” in the paragraph spanning pages 43-44 which does not provide clear boundaries on what amino acids are considered hydrophilic and hydrophobic. Further, “a hydrophobic amino acid less hydrophobic than alanine” is indefinite relative terminology because it is unclear what the hydrophobicity of alanine is as hydrophobicity is pH-dependent (MPEP § 2173.05(b)). Claims 1, 33, and 54 are rejected for indefiniteness.
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Claim 5 recites SEQ ID NO: 55 comprising at least one amino acid substitution at the amino acid position corresponding to Q16 of SEQ ID NO: 102. As shown in Fig. 2 of the drawings (as pictured below), the amino acid positions of SEQ ID NOs: 99, 100, and 101 as they correspond to SEQ ID NO: 102 (residues 14-30 as listed in the top row) are clearly defined. Note, SEQ ID NO: 99 is the unstapled precursor of SEQ ID NO: 1, SEQ ID NO: 100 is the unstapled precursor of SEQ ID NO: 95, and SEQ ID NO: 101 is the unstapled precursor of SEQ ID NO: 55 (specification page 33). However, residue Q16 of SEQ ID NO: 101 (equivalent to unstapled SEQ ID NO: 55) does not exist as SEQ ID NO: 101 begins with L17. Therefore, it is unclear how a substitution could be made at position Q16 of SEQ ID NO: 55 as recited in Claim 5.
Claim 54 recites “a conservative amino acid substitution thereof” and “a conservative substitution thereof.” Note, “a conservative amino acid substitution thereof” and “a conservative substitution thereof” are interpreted as synonymous. However, the structural metes and bounds of what is encompassed by “a conservative amino acid substitution” are unclear. Different references in the art prior to filing define conservative amino acid substitutions differently. For example, Gonzalez et al. WO 99/57141 defines that conservative amino acid substitutions for Ser are Thr, Gly, and Asn (Table 1) wherein Maslen et al. WO 2007/086889 defines that conservative amino acid substitutions for Ser are Gly, Asp, Glu, Asn, Gln, Ala, and Thr (Table 1). The specification defines a “conservative amino acid substitution” as a substitution that replaces one amino acid with another amino acid residue having a similar side chain and lists non-limiting examples (page 44, lines 9-18). Therefore, it is unclear what amino acids are encompassed by “a conservative substitution thereof.” Further, Claim 54 lists multiple amino acids wherein only some of the amino acids are joined with the phrase “a conservative substitution thereof.” It is unclear which amino acids this phrase applies to. For example, “Xaa8 is Asp or a conservative amino acid substitution thereof, Glu, Ala, or Asn or a conservative amino acid substitution thereof” could be interpreted to mean that Xaa8 is (1) Asp or a conservative amino acid substitution of Asp; (2) Glu; (3) Ala; or (4) Asn or a conservative amino acid substitution of Asn. Alternatively, the same phrase could be interpreted to mean that Xaa8 is (1) Asp or a conservative amino acid substitution of Asp; (2) Glu or a conservative amino acid substitution of Glu; (3) Ala or a conservative amino acid substitution of Ala; or (4) Asn or a conservative amino acid substitution of Asn. The broadest reasonable interpretation is that “or a conservative substitution thereof” applies to all listed amino acids and a conservative amino acid substitution comprises any amino acid. However, clarifying correction is required.
Claim 75 recites “a means for preferentially binding HDMX over HDM2” that invokes 35 U.S.C. 112(f). However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. No association between the structure and the function can be found in the specification because “a means for preferentially binding HDMX over HDM2” is not defined. Therefore, Claim 75 is indefinite and is rejected under 35 U.S.C. 112(b).
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Note, a peptide that preferentially binds to HDMX over HDM2 (as defined in Claim 1) and a peptide that selectively binds to HDMX (as defined in Claim 23) are interpreted as synonymous based on specification page 3, lines 19-20 that recite “these peptides and stapled peptides selectively (preferentially) bind HDMX over HDM2. The broadest reasonable interpretation of preferentially binding to HDMX over HDM2 is any increase in binding affinity to HDMX as compared to HDM2 as measured by methods known in the art prior to filing, even a non-significant change.
Note, “with 3 to 10 amino acid substitutions” as defined in line 4 of Claim 1 is interpreted as synonymous to “except for 3 to 10 amino acid substitutions” as defined in lines 6 and 8 of Claim 1. Both phrases are interpreted to mean that the peptide comprises SEQ ID NO: 101 comprising 3 to 10 amino acid substitutions, SEQ ID NO: 99 comprising 3 to 10 amino acid substitutions, or SEQ ID NO: 100 comprising 3 to 10 amino acid substitutions.
Note, stapled peptides, stitched peptides, and stapling amino acids are all known in the art prior to filing as evidenced by specification pages 61-62. Note, “a charged amino acid” as recited in Claims 1 and 54 is defined by Millipore Sigma Amino acids Reference Chart (2026) as Asp, Glu, Arg, His, or Lys. Note, “(SEQ ID NO: 84)-naphthalene-(SEQ ID NO: 238)” as recited in Claims 23 and 32 is interpreted to comprise SEQ ID NO: 84 linked to SEQ ID NO: 238 by a naphthalene. Note, “an amino acid sequence set forth in” encompasses any fragment of two or more amino acid residues within the recited sequence.
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, 5, 23, 32-34, 54, 61, and 75 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.
The claims are directed to a genus of peptides that comprises substantial structural variation. Claims 1 and 5 are directed to peptides comprising up to 10 amino acid substitutions; Claim 54 comprises peptides with various different amino acid sequences; and Claim 61 comprises peptides with at least two amino acid substitutions and various cross-linking structures. The broadest reasonable interpretation for the claimed substitutions is that any combination of amino acids can be substituted with any other naturally occurring or non-naturally occurring amino acids. Claims 23, 32, 61 recite “an amino acid sequence set forth in any of one SEQ ID NOs:” wherein “an amino acid sequence set forth in” encompasses any fragment of two or more amino acid residues within the recited sequence. Therefore, Claims 23, 32, and 61 are directed to a genus of peptides and fragments thereof. Note, potential claim language to claim the sequences in their entirety could recite “an amino acid sequence comprising any one of SEQ ID NOs:”
As described above, the disclosure does not provide adequate structure to perform the function encompassed by “a means for preferentially binding HDMX over HDM2” in Claim 75. The specification does not demonstrate that Applicant has made an invention that achieves the claimed function because the invention is not described with sufficient detail that one of ordinary skill in the art can reasonably conclude that the inventor had possession of the claimed invention.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. In order to provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
From the specification, select peptides were synthesized (see sequences in Figs. 3A-4B); however, not all of the peptides preferentially bind HDMX over HDM2 as required by the claims. For example, some substitutions at L26 (like L26A, L26R, and L26E) retained selective binding for HDMX wherein other substitutions at L26 (like L26F, L26I, and L26NorLeu) retained binding to HDM2 (Example 1). Further, double and triple mutants were evaluated and some combinations “unexpectedly” restored dual HDM2/HDMX interaction such as K24E/E28A (SEQ ID NO: 47) (Example 4). Thus, the specification teaches a limited number of peptide variants, and of those variants, only a fraction achieved the required preferential binding function. These examples highlight how altering peptide structure (such as amino acid substitutions) can impact peptide function in unpredictable ways.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (MPEP § 2163.05.Ib). The specification teaches three amino acid substitutions (L26A, L26R, and L26E) that maintain HDMX-selective binding across SAH-p53-4 (SEQ ID NO: 1), SAH-p53-8 (SEQ ID NO: 95), and ATSP-7041 (SEQ ID NO: 55) (Example 1). Describing three amino acid substitutions without any other distinguishing identifying characteristics or structure-to-function attributes does not provide adequate written description of the claimed genus of peptides. Therefore, in view of the case law directed to an appropriate number of representative species, claims 1, 5, 23, 32-34, 54, 61, and 75 are rejected for insufficient written description.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Claims 1, 5, 23, 32-34, 54, 61, and 75 are also rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the specific species of peptides comprising SEQ ID NOs: 1, 55, 95, or 99-101 with substitutions L26A, L26R, or L26E, does not reasonably provide enablement for the genus of peptides comprising up to 10 amino acid substitutions, at least two amino acid substitutions, or various sequence fragments. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
MPEP § 2164.01(a) states that there are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure
does not satisfy the enablement requirement and whether any necessary experimentation is
“undue”. These factors include, but are not limited to:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims and nature of the invention:
The nature of the invention is complex. As understood with the broadest reasonable interpretation, the claims encompass a genus of peptides that comprises substantial structural variation. Claims 1 and 5 are directed to peptides comprising up to 10 amino acid substitutions; Claim 54 comprises peptides with various different amino acid sequences; and Claim 61 comprises peptides with at least two amino acid substitutions and various cross-linking structures. Any combination of amino acids can be substituted with any other naturally occurring or non-naturally occurring amino acids. Claims 23, 32, 61 recite “an amino acid sequence set forth in any of one SEQ ID NOs:” which encompass a genus of peptides and fragments thereof. Claim 75 is directed to any means for preferentially binding HDMX over HDM2 and has no required structure.
When analyzing the scope of enablement, the claims are analyzed with respect to the teachings of the specification and are to be "given their broadest reasonable interpretation consistent with the specification." See MPEP 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
The state of the prior art and level of predictability in the art:
The level of predictability in the art depends, most importantly, on whether the claimed invention can be practiced by one of ordinary skill in the art. In AMGEN INC. ET AL. v. SANOFI ET AL. (No. 21-757, decided May 18, 2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies that perform these two functions. The case law applies to the instant claims which encompass a genus of peptides that are required to preferentially bind HDMX over HDM2, yet the inventors have only disclosed three amino acid substitutions that can accomplish this function (L26A, L26R, or L26E) (Example 1).
In Amgen, the Supreme Court has stated: “An antibody' s structure does much to dictate its function—its ability to bind to an antigen and, in some instances, to block other molecules in the body from doing the same. Different antibodies have different binding and blocking capacities based on the amino acids that compose them and their three-dimensional shapes.” See id., at 11–12. Despite recent advances, aspects of antibody science remain unpredictable. For example, scientists understand that changing even one amino acid in the sequence can alter an antibody' s structure and function. See id., at 14. But scientists cannot always accurately predict exactly how trading one amino acid for another will affect an antibody' s structure and function. Ibid. The unpredictability of amino acid mutations extends to the structurally-stabilized peptides with required binding functions in the instant application.
The case law shows a continued lack of predictability even after the effective filing date of the instant invention, and there is no support in the Applicant’s disclosure leading one of ordinary skill to overcome the lack of predictability in the genus of amino acid variations claimed. The specification provides no guidance or direction for which the amino acid sequences may be substituted or fragmented such that the functional properties of the invention are preserved (preferentially bind HDMX over HDM2).
Level of skill in the art:
The level of skill would be high encompassing protein synthesis and mutagenesis, competitive binding assays, etc.
Amount of direction provided by inventor and the existence of working examples:
From the specification, select peptides were synthesized (see sequences in Figs. 3A-4B); however, not all of the peptides preferentially bind HDMX over HDM2 as required by the claims. For example, some substitutions at L26 (like L26A, L26R, and L26E) retained selective binding for HDMX wherein other substitutions at L26 (like L26F, L26I, and L26NorLeu) retained binding to HDM2 (Example 1). Further, double and triple mutants were evaluated and some combinations “unexpectedly” restored dual HDM2/HDMX interaction such as K24E/E28A (SEQ ID NO: 47) (Example 4). Thus, the specification teaches a limited number of peptide variants, and of those variants, only a fraction achieved the required preferential binding function. The specification further teaches that identifying compounds that enhance HDMX binding activity, retain HDMX binding selectivity, and optimize cellular uptake is unpredictable and requires “substantial compound iteration and testing” (Example 4, paragraph 1).
Three representative species of peptide variants (L26A, L26R, or L26E) are not sufficient to describe the genus of possible peptides encompassed by the claims, especially considering the unpredictability of the structure-to-function correlation. As evidenced by specification Example 4, paragraph 1, a person having ordinary skill in the art would have to make a substantial inventive contribution in order to make and characterize a representative number of peptide species to encompass the claimed genus.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
In light of the unpredictability surrounding the claimed subject matter, the undue breadth of the claimed invention’s intended use, and the lack of adequate guidance, one wishing to make and practice the presently claimed invention would be unable to do so without engaging in undue experimentation. Given that structure is essential to function, a person having ordinary skill in the art would have to perform further experimentation to systematically make the structural variants encompassed by the claims and screen their individual binding characteristics in order to practice the invention commensurate with the scope of the claims.
The instant specification does not enable the invention to make and use the entire genus of peptides; therefore, Claims 1, 5, 23, 32-34, 54, 61, and 75 are rejected.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 5, 23, 32-34, 54, and 61 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Walensky et al. WO 2017/165617.
Claim 1 is directed to a peptide comprising SEQ ID NO: 101 comprising two substitutions with stapling amino acids and a B26A substitution. Claim 5 is directed to SEQ ID NO: 55 comprising a substitution at B26. Claims 23 and 32 are directed to a peptide comprising SEQ ID NO: 57. Claims 33-34 are directed to pharmaceutical compositions of the peptides of Claims 1 and 5, respectively. Claim 54 is directed to a peptide comprising LTF8EYWAQAXSAA wherein 8 and X are cross-linked stapling amino acids. Claim 61 is directed to a peptide comprising a cross-linked amino acid sequence having Formula (I) and SEQ ID NO: 101. Note, it is interpreted that the peptides’ functional properties such as preferentially binding HDMX over HDM2 are inherent to the peptides’ structures (MPEP § 2112.01).
In regard to Claims 1, 5, 23, 32-34, 54, and 61, Walensky teaches a peptide termed ALRN-7041 comprising LTF*EYWAQZ*SAA wherein “*” denotes the location of stapling amino acids and Z is cyclobutyl alanine (Cba) (Example 4) which is 100% identical to instant SEQ ID NO: 55 (the stapled version of instant SEQ ID NO: 101). Walensky further teaches a variant peptide thereof termed “ALRN-7041L26A” comprising LTF*EYWAQA*SAA (Example 4 and Fig. 7). ALRN-7041L26A taught by Walensky reads on the peptide of instant Claims 1, 5, and 54 and is 100% identical to instant SEQ ID NO: 57 (Claims 23 and 32). The internally cross-linked (ICL) p53 transactivation domain-based inhibitor peptides (PTAIB) (targeting HDM2 and HDMX) of Walensky can be formulated as pharmaceutical compositions in combination with pharmaceutically acceptable carriers (page 1 lines 10-12; page 39 line 33 to page 40 line 24). The cross-linked stapling amino acids can comprise Formula (I) (page 16 line 18 to page 19 line 14) wherein Walensky Formula (I) is identical to instant Formula (I) of Claim 61.
Therefore, Claims 1, 5, 23, 32-34, 54, and 61 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Walensky.
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.
1. Claims 5, 23, 32, 34, 54, and 75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 24 of U.S. Patent No. 8,889,632.
The instant claims are directed to a peptide comprising SEQ ID NO: 1 wherein residues 7 and 14 are stapling amino acids and the peptide comprises 1 to 10 amino acid substitutions (Claims 5 and 54). Claims 23 and 32 are directed to SEQ ID NOs: 21, 57, 96, or fragments thereof (see above explanation of “set forth in”). Claim 34 recites a pharmaceutical composition comprising the peptide of Claim 5 and a pharmaceutically acceptable carrier. Claim 75 recites a pharmaceutical composition comprising a means for selectively binding HDM2 and HDMX and a pharmaceutically acceptable carrier.
The patented claims are directed to a peptide comprising SEQ ID NO: 2 wherein residues 7 and 14 are cross-linked by Formula (I) (Claim 1). The peptide can comprise up to 6 amino acid substitutions wherein residue 13 (equivalent to L26 in the instant application) is not substituted (Claim 1). The peptide can comprise a pharmaceutically acceptable salt thereof (Claim 1). Claim 24 recites wherein the peptide or pharmaceutically acceptable salt thereof of Claim 1 binds to HDMX and HDM2. Note, patented SEQ ID NO: 2 with cross-linked stapling amino acids at residues 7 and 14 is 100% identical to instant SEQ ID NO: 1, and patented SEQ ID NO: 2 reads on a fragment of instant SEQ ID NO: 21.
Thus, the instant claims are either anticipated and/or rendered obvious by the Patented claims.
2. Claims 5, 23, 32, 34, 54, 61, and 75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-4 of U.S. Patent No. 10,822,374 in view of Walensky et al. WO 2017/165617.
Instant claims 5, 23, 32, 34, 54, and 75 are recited above. Instant Claim 61 is directed to a peptide comprising SEQ ID NO: 100 wherein two amino acids are stapled using the cross-linking of Formula (I).
Patented Claim 1 encompasses peptides comprising instant SEQ ID NOs: 99, 100, 1, or 95 wherein L26 is held constant. The peptide binds HDMX (Claim 1). Patented Claim 3 is directed to a peptide comprising SEQ ID NO: 10 and further comprises 1, 2, or 3 amino acid substitutions. The peptide can be combined with a pharmaceutically acceptable carrier (Claim 4). Note, patented SEQ ID NO: 10 is 100% identical to instant SEQ ID NO: 95 (the stapled version of instant SEQ ID NO: 100). Patented SEQ ID NO: 10 reads on a fragment of instant SEQ ID NO: 96.
The patented claims teach wherein two amino acid residues are stapled/cross-linked (Claim 1) but do not teach wherein the cross-linkage is specifically of Formula (I). Walensky teaches cross-linked stapling amino acids that comprise Formula (I) (page 16 line 18 to page 19 line 14) wherein Walensky Formula (I) is identical to instant Formula (I) of Claim 61. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (known cross-linking structure of Formula (I) for the cross-linked amino acids) (See MPEP 2144.06-II). Thus, the instant claims are either anticipated and/or rendered obvious by the Patented claims in view of Walensky.
3. Claims 5, 23, 32, 34, 54, and 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 124 and 135 of copending U.S. App. No. 18/113,539 in view of Walensky et al. WO 2017/165617.
Instant claims 5, 23, 32, 34, 54, and 61 are recited above.
The copending claims recite a stapled peptide that comprises SEQ ID NO: 6 comprising 1 to 3 amino acid substitutions (Claim 124) and a pharmaceutical composition comprising the peptide and a pharmaceutically acceptable carrier (Claim 135). Note, copending SEQ ID NO: 6 is 100% identical to instant SEQ ID NO: 55 (the stapled version of instant SEQ ID NO: 101). Copending SEQ ID NO: 6 reads on a fragment of instant SEQ ID NO: 57.
The copending claims teach wherein two amino acid residues are stapled/cross-linked (Claim 124) but do not teach wherein the cross-linkage is specifically of Formula (I). Walensky teaches cross-linked stapling amino acids that comprise Formula (I) (page 16 line 18 to page 19 line 14) wherein Walensky Formula (I) is identical to instant Formula (I) of instant Claim 61. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (known cross-linking structure of Formula (I) for the cross-linked amino acids) (See MPEP 2144.06-II). Thus, the instant claims are either anticipated and/or rendered obvious by the copending claims in view of Walensky.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
4. Claims 5, 23, 32, 34, 54, and 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending U.S. App. No. 18/315,725 in view of Walensky et al. WO 2017/165617.
Instant claims 5, 23, 32, 34, 54, and 61 are recited above.
The copending claims recite a stapled peptide that comprises SEQ ID NO: 14 (Claim 1) wherein copending SEQ ID NO: 14 is 100% identical to instant SEQ ID NO: 55 (the stapled version of instant SEQ ID NO: 101) further comprising B26L and S28A substitutions. Copending SEQ ID NO: 14 reads on a fragment of instant SEQ ID NO: 57. The peptide is administered to human subjects (Claim 1) which makes obvious formulating the peptide as a pharmaceutical composition.
The copending claims teach wherein two amino acid residues are stapled/cross-linked (Claim 1) but do not teach wherein the cross-linkage is specifically of Formula (I). Walensky teaches cross-linked stapling amino acids that comprise Formula (I) (page 16 line 18 to page 19 line 14) wherein Walensky Formula (I) is identical to instant Formula (I) of instant Claim 61. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (known cross-linking structure of Formula (I) for the cross-linked amino acids) (See MPEP 2144.06-II). Thus, the instant claims are either anticipated and/or rendered obvious by the copending claims in view of Walensky.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Note, no nonstatutory double patenting rejection is made in view of U.S. Patent No. 9,527,896 or U.S. Patent No. US 10,202,431 because the patented claims are directed to a cross-linked peptide comprising 8 contiguous amino acids and the instant peptides comprise at least 12 amino acids.
Allowable Subject Matter
No claim is allowed. However, a structurally-stabilized peptide comprising SEQ ID NO: 96 is enabled and free of the prior art specifically because of the L26E substitution.
Conclusion
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675