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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant's arguments filed 9/17/2025 have been fully considered but they are not persuasive.
Applicant’s submit that the limitation a “synthetic peptide” is sufficient to overcome the rejections under 35 U.S.C. 101 and 102, as a synthetic peptide is “not natural” and peptides listed as being from organisms such as Homo sapiens are not synthetic. The Examiner disagrees. As there is no definition for a “synthetic peptide” in the instant specification, the broadest reasonable interpretation of the claims would allow for synthetic peptides comprising or consisting of naturally-occurring sequences typically found within living organisms that are derived from non-natural sources, i.e., peptides generated in a laboratory. Both Rosen et al. (WO00/55350) and Lester et al. (WO2023/178241A2) from the previous office action teach that the peptides taught can be prepared through recombinant or synthetic means, thus reading on synthetic peptides (see of Pg 8, final paragraph of Rosen and Examples 7 and 13 of Lester).
Regarding the previous rejections under 35 U.S.C. 102, the Examiner does agree that the amended claims overcome the rejections of the previous office action. However, a new ground(s) of rejection is made below in view of the amended claims.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-13, drawn to synthetic peptides, and the species SEQ ID NO: 7 and Alzheimer’s Disease, in the reply filed on 4/21/2025 is acknowledged.
In the previous action, the elected species was broadened to include SEQ ID NO: 3 along with the previously elected SEQ ID NO: 7.
Claim Status
Claims 1-5, 7-9, and 12-14 are pending. Claims 1, 2, 5, 8, and 12 are currently amended. Claims 6, 10, and 11 have been cancelled. Claims 3, 4, 7, and 14 are withdrawn and currently amended.
Priority
The Application claims priority to the provisional application 63/321,980 filed on 3/21/2022.
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.
Claims 1, 2, 5, 8, 9, 12, and 13 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.
Claim 1 recites a peptide consisting of: 1) a first sequence consisting of 30 or more serine residues, 2) a second sequence at the C- or N-terminus of the first sequence comprising 4-7 amino acids and a kinase docking site, and optionally (a) a degradation module that promotes degradation of a bound pathological tau aggregate, (b) a cell penetrating peptide bound to the first or second sequence, and/or (c) 1-2 additional sequences at the C- or N-terminus of the peptide each containing less than 20 residues, wherein the additional sequences are optionally connected to the first or second sequence via a linker, and wherein the peptide is a synthetic peptide. The scope of this claim is indefinite as there are inconsistencies between the closed and open limitations of the claim. For instance, the peptide that consists of 1) and 2) but may also include (a), (b), and/or (c) without explicit size limitations on (a) or (b) and with (c) only having size limitations on the additional sequences added but not on the linker used to connect (c) to 1) or 2).
By virtue of their dependency on claim 1, claims 2, 5, 8, 9, 12, and 13 are also hereby rejected for this same reasoning.
For purposes of examination, the claim has been interpreted as a peptide consisting of 1) a first sequence consisting of 30 or more serine residues and 2) a second sequence consisting of 4-7 amino acids that includes a kinase docking site.
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 1, 2, 5, 8, 9, 12, and 13 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.
Claim 1 recites a peptide consisting of a first sequence consisting of 30 or more serine residues, a second sequence at the C- or N-terminus of the first sequence comprising 4-7 amino acids and a kinase docking site, and optionally (a) a degradation module that promotes degradation of a bound pathological tau aggregate, (b) a cell penetrating peptide bound to the first or second sequence, and/or (c) 1-2 additional sequences at the C- or N-terminus of the peptide each containing less than 20 residues, wherein the additional sequences are optionally connected to the first or second sequence via a linker, and wherein the peptide is a synthetic peptide. The rejection is based on the limitation “(a) a degradation module that promotes degradation of a bound pathological tau aggregate”, which recites a feature of the peptide by functional rather than structural language. There is nothing further in the claim to indicate the structural feature(s) required to meet this functional limitation, and describing an invention by function is insufficient to meet the written description requirement.
Per MPEP 2163(II)(3)(a), for some biomolecules, examples of identifying characteristics include a sequence, structure, binding affinity, binding specificity, molecular weight, and length. Although structural formulas provide a convenient method of demonstrating possession of specific molecules, other identifying characteristics or combinations of characteristics may demonstrate the requisite possession. As explained by the Federal Circuit, "(1) examples are not necessary to support the adequacy of a written description; (2) the written description standard may be met … even where actual reduction to practice of an invention is absent; and (3) there is no per se rule that an adequate written description of an invention that involves a biological macromolecule must contain a recitation of known structure." Falkner v. Inglis, 448 F.3d 1357, 1366, 79 USPQ2d 1001, 1007 (Fed. Cir. 2006); see also Capon v. Eshhar, 418 F.3d at 1358, 76 USPQ2d at 1084 ("The Board erred in holding that the specifications do not meet the written description requirement because they do not reiterate the structure or formula or chemical name for the nucleotide sequences of the claimed chimeric genes" where the genes were novel combinations of known DNA segments.). However, the claimed invention itself must be adequately described in the written disclosure and/or the drawings. For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
Applicants have disclosed that degradation modules may include degron sequences but not disclosed any specific degron sequences ([0027-0028]). No other degradation modules are contemplated within the instant specification, and the claims listed above are written such that they contemplate or include additional compounds that retain the same functional characteristics beyond these limited examples. Thus, the instant specification does not provide adequate written description to possess the broad genus described above.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, 5, 8, and 9 are rejected under 35 U.S.C. 101 because they are directed to a judicial exception.
The Supreme Court has given a three-part test for patent eligibility (see flowchart of MPEP 2106(III)):
Are the claims drawn to a process, machine, manufacture, or composition of matter?
2a) If the claims pass the first test, are the claims drawn to a judicial exception (a law of nature, a natural phenomenon (product of nature), or an abstract idea)?
2b) If a judicial exception applies, do the claims recite additional elements that amount to significantly more than the judicial exception?
Applying the three-part test to the instant claims:
Regarding 1), the claims are drawn to peptides, which are compositions of matter.
Regarding 2a), the peptides claimed are products of nature.
The claims are drawn to peptides comprising a first sequence consisting of M serine residues, where M is at least 30; a second sequence at the C- or N-terminus of the first sequence, the second sequence comprising 4-7 amino acids, the 4-7 amino acids including a kinase docking site for a kinase, and wherein the peptide is a synthetic peptide. This reads on multiple isoforms of serine/arginine repetitive matrix protein 2. Isoform X7 is shown below aligned to the instant SEQ ID NO: 3, which consists of an N-terminal KRKRR kinase docking site sequence and a run of 42 serine residues:
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130
588
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Greyscale
As described above, synthetic peptides generated in a laboratory setting can still retain the same sequence as those that are naturally occurring. As there is no significant difference between these naturally-occurring in those organisms and those made in a laboratory setting, synthetic peptides still read on natural products.
Further, while these proteins may be longer than the limits imposed by the claims, based on the transitional phrase “consisting of”, in Ass’n for Molecular Pathology v Myriad Genetics, the Supreme Court stated that fragments of a biopolymer still trigger this statute. Thus, the fact that these sequences are longer than those claimed does not make the rejection invalid, unless the fragment is significantly different from the full-length polypeptide.
Regarding 2b), none of the claims above integrate the peptides into practical applications. At most, claim 2 recites functional attributes endowed by the peptides without significantly more. As such, they do not contain elements added to the judicial exception sufficient to render the claims significantly more than the exception.
Taken together, the claims are drawn to patent ineligible subject matter and are rejected here.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 1, 2, 5, 8, 9, 12, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over DiMaio et al. (US 2021/0206811 A1, published 7/8/2021) and Van Alstyne et al. (WO2023/178241 A2, effectively filed 3/16/2022; referred to as Lester et al. in the previous office action).
DiMaio teaches compositions and methods for facilitating cell penetration of a cargo molecule via cell penetrating peptides (CPPs). CPPs can be covalently linked at the N- or the C-terminus to transport cargo ([0074]). DiMaio teaches several cell penetrating peptides, including SEQ ID NO: 18, 37, 79-81, and 131, all of which are 4-7 amino acids in length and comprise the instant SEQ ID NO: 1 (Sequence Listing). The instant specification indicates that the instant SEQ ID NO: 1 is a kinase docking site ([0023]).
DiMaio does not teach joining the above sequences to a polyserine repeat consisting of at least 30 serine residues.
Van Alstyne teaches methods and compositions for targeting tau aggregates or components thereof using polyserine repeat sequences and/or serine-rich sequences, which may be coupled with a heterologous peptide, to target tau aggregates or components thereof (Abstract). Polyserine motifs can be used to target fusion proteins to tau aggregates and thereby treat and/or limit them (Pg 2, lines 28-29). The polyserine repeat of the invention may include a homologous polyserine repeat of 10-50 or more consecutive serine residues, with a preferred embodiment having 20-42 consecutive serine residues (Pg 11, lines 6-12; Pg 13, lines 2-11). The heterologous peptide bound to the polyserine repeat may be selected from a kinase that can post-translationally modify tau aggregates (Pg 3, lines 20-24). The creation of such an unnatural fusion protein also reads on a synthetic peptide.
Thus, regarding claims 1, 5, 8, and 9, DiMaio teaches peptide sequences comprising cell penetrating peptides/kinase docking sites that can be covalently linked to the N- or C-terminus of cargo molecules to transport them into cells. Van Alstyne teaches polyserine conjugates comprising polyserine repeat sequences of up to or greater than 50 serine residues and a kinase to post-translationally modify tau aggregates, thereby limiting or treating them. Therefore, it would be prima facie obvious to attach any of the above listed sequences taught by DiMaio to either termini of the polyserine repeat taught by Van Alstyne in order to effectively transport the polyserine repeat into cells and treat tau aggregates by attracting endogenous kinases. One skilled in the art would have a reasonable expectation of success as DiMaio established a series of CPPs useful for transporting cargo into cells that are also kinase docking sites and Van Alstyne established that kinases themselves could be attached to polyserine repeats to treat tau aggregates.
Regarding claim 2, DiMaio and Val Alstyne do not explicitly teach that the kinase docking site is configured such that the kinase phosphorylates an adjacent serine reissued, thereby setting off a phosphorylation cascade. However, one of ordinary skill in the art would recognize that the function of a kinase is to phosphorylate amino acids such as serine. Thus, connecting a kinase docking site to a sequence of repeating serine residues would necessarily result in the phosphorylation of the polyserine repeat.
Regarding claims 12 and 13, Van Alstyne teaches that the peptides can be incorporated into an expression vector (Pg 3, lines 25-29; Pg 10, lines 1-6; claim 49). Van Alstyne further explains that such expression vectors can be delivered to a target cell (Pg 3, lines 25-29).
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sara E Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa L Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658