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 .
Election/Restrictions
Applicant’s election of SEQ ID NO: 2 in the reply filed on August 24, 2026, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
An a-synuclein inhibitor consisting of SEQ ID NO: 2 is free of the prior art but is subject to a rejection for non-statutory double patenting. The search was extended and prior art was found on: 1) an a-synuclein inhibitor comprising SEQ ID NO: 2, and 2) an a-synuclein inhibitor consisting of KIDDTE, which is a peptide consisting of six consecutive amino acid residues of instant SEQ ID NO: 1, wherein the peptide includes instant SEQ ID NO: 3, and two amino acid substitutions thereof. Therefore, the search was not extended further in accordance with MPEP § 803.02.
Claim Interpretation
BRI of “An a-synuclein aggregation inhibitor comprising a peptide (A1) or (A2)” includes peptides wherein (A1) or (A2) is embedded in longer amino acid sequences. This interpretation is based on MPEP § 2111.03(II) which states that "consists" in the body of the claim does not limit the open-ended "comprising" language in the claims.
BRI of “an amino acid of sequence of SEQ ID NO: 2 or 3” includes full-length SEQ ID NOs: 2 and 3 as well as fragments thereof because of the indefinite article “an”.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
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.
Issues Relevant to Both Written Description and Enablement Presented Once for Brevity
1) Scope of the Claims
The claims are drawn to a-synuclein aggregation inhibitors and pharmaceutical compositions and methods for treating or preventing a-synuclein aggregation diseases comprising the inhibitors.
Claim 1 is drawn to an a-synuclein aggregation inhibitor comprising a peptide (A1) or (A2). (A1) is a peptide consisting of 6 or more consecutive amino acid residues in an amino acid sequence of SEQ ID NO: 1, wherein the peptide includes an amino acid of sequence of SEQ ID NO: 2 or 3. The limitation “an amino acid of sequence of SEQ ID NO: 2 or 3” includes full-length SEQ ID NOs: 2 and 3 as well as fragments thereof because of the indefinite article “an”. (A2) is a peptide having an amino acid sequence obtained by performing deletion, substitution, or addition of 1 or 2 amino acids on the amino acid sequence of (A1). Therefore, the claimed a-synuclein aggregation inhibitor is a peptide of any length that comprises any six amino acid fragment of SEQ ID NO: 1 that also includes at least a dipeptide of SEQ ID NOs: 2 or 3, or a peptide obtained by performing a deletion, substitution, or addition of 1 or 2 amino acids thereof. The number of amino acid sequences that meet these structural requirements is enormous.
However, only those sequences meeting the structural and functional requirements of the genus are encompassed by the claims. Therefore, claim 1, and dependent claims 2-12 and 26 encompass all of the amino acid sequences meeting the structural requirements above that are also able to inhibit a-synuclein aggregation. Claims 4-8, 12, and 26 require that the peptide is capable of treating or preventing a-synuclein aggregation disease caused by a-synuclein aggregation. Claim 7 requires that the disease is Parkinson’s disease.
In claims 9-10 and 12, a test subject may be a non- living-being-derived test subject that does not contain cells and the like, or a living-being-derived test subject that is cells such as brain cells, tissue such as brain tissue, or an organism. In claim 11, the test subject is a human or non-human animal.
2) Actual reduction to practice/Working examples
The instant specification includes a limited reduction to practice: a single peptide in the scope of the claims, YS-11, which consists of SEQ ID NO: 2, inhibits a-synuclein aggregation in vitro (Figures 3 and 4B), dissociates a-synuclein aggregates (Figure 5B), ameliorates cognitive decline in an animal model of Parkinson’s Disease (Figure 6), ameliorates motor dysfunction in an animal model of Parkinson’s Disease (Figure 7), and ameliorates the impact of a-synuclein aggregation on cell viability (Figure 10).
3) Predictability in the art
There is a high level of unpredictability and complexity associated with the structure-activity relationship of a-synuclein aggregation inhibitors comprising the claimed peptides. The prior art of WO 2018/005867 A2, EP 406 279 B1, and WO 2010/103515 A1 each disclose a-synuclein aggregation inhibitors that are structurally unrelated to the claimed inhibitors. The prior art of US 2021/0030858 A1 and US 6,358,920 each disclose peptides that meet the structural requirements of the claims but are silent on the a-synuclein aggregation inhibitor function. Therefore, these references cannot guide a POSITA on the structure-function correlation of the claimed peptides.
In addition, there is a high level of unpredictability and complexity associated with using inhibitors of a-synuclein aggregation to treat related diseases including Parkison’s Disease (specification [0002]-[0003]). The post-filing date art of Horne et al. (Nature Chemical Biology volume 20, pages 634–645 (2024) ) notes that despite significant effort in identifying a-synuclein aggregation inhibitors, there are no approved disease-modifying therapies currently available to patients with Parkinson’s Disease (introduction).
4) Guidance in the specification/Structure-function correlation
The specification does not describe a general correlation between structure and function for the claimed genus. The role of each of the amino acids of SEQ ID NOs: 1-3 in a-synuclein aggregation inhibition are not described. As a result, it is impossible to predict, based on the specification, how changing any position will affect the claimed function.
Claims 1-12 and 26 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Only a peptide consisting of SEQ ID NO: 2 was reduced to practice for treating an animal model of Parkinson’s Disease. As discussed above the claim scope is enormous given the breadth of structural limitations and complexity of functional limitations in the claims. Therefore, one of ordinary skill in the art would not consider a peptide consisting of SEQ ID NO: 2 to be representative of the full scope of the claimed genus of inhibitors. Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the claimed activity and therefore do not describe which substitutions, deletions or additions could be made while preserving function. Understanding the physical basis for the claimed activity is critical to determining which of the sequences that meet the structural requirements of the genus also meet the functional requirements of the genus.
The specification does not describe a general correlation between structure and function for the claimed genus. The role of the amino acids of SEQ ID NOs: 1-3 are not described. As a result, it is impossible to predict, based on the specification, how changing any position will affect the claimed functions.
As described above there is a high degree of unpredictability in the prior art with respect to a-synuclein aggregation inhibitor structure-function, and the use of such molecules to treat any disease, including Parkison’s Disease. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless peptides that meet the structural requirements of the claims would also be able to perform the complicated claimed functions. The specification does not make clear which peptides are in the genus and which are not because it does not describe the physical basis for the claimed activity. In other words, the specification does not describe which peptides to make.
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention. In conclusion, only a peptide consisting of SEQ ID NO: 2 meets the written description provision of 35 U.S.C. 112(a).
Claims 1-12 and 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for using a peptide consisting of SEQ ID NO: 2 to treat Parkinson’s Disease in a subject in need thereof, does not reasonably provide enablement for the treatment or prevention of any other conditions with this peptide or the use of any other claimed peptide. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Factors (2)-(8) are discussed above.
The scope of the claimed a-synuclein aggregation and therapeutic indications are extremely broad relative to the narrow reduction to practice in the specification. That fact combined with the level of unpredictability and complexity in the art, the relative skill in the art, and the lack of specific guidance in the specification, poses an undue burden of experimentation on one of ordinary skill in the art seeking to practice the claimed methods. The specification is an invitation to undertake a research program to identify additional compositions that could be used to carry out different embodiments of the claims. As such, the specification fails to meet the enablement provision of 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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 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 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Evgin et al. (US 2021/0030858 A1; hereafter “EVGIN”).
EVGIN teaches the peptide YKNMRETLVYLTHLDYVDTEI (SEQ ID NO: 291), which is a peptide comprising instant (A1) wherein (A1) consists of SEQ ID NO: 2 (underlined). BRI of claim 1 does not exclude the additional, unrecited N-terminal sequence YKNM or the additional, unrecited C-terminal sequence YVDTEI because of the open transitional phrase in the preamble of the claim (see MPEP § 2111.03(II)). Therefore, SEQ ID NO: 291 of EEVGIN meets all of the structural requirements of instant claim 1.
MPEP § 2112.01(II) states: "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
In the instant case, the prior art teaches a peptide that meets all of the structural requirements of instant claim 1 but is silent as to its function as an a-synuclein aggregation inhibitor. Because the prior art teaches a composition that meets all of the structural and physical limitations of the claim, the claimed property of a-synuclein aggregation inhibition is inherent to the prior art composition. The inventors have found a new property of an old composition and such a discovery does not constitute a new composition.
Therefore, EVGIN anticipates claim 1.
Regarding claim 2-3, SEQ ID NO: 291 is a peptide wherein a peptide of (A1) includes SEQ ID NOs: 2. Therefore, EVGIN anticipates claim 2.
Claims 1, 3-4, 6-8, and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Blaschuk et al. (U.S. Patent No. 6,358,920 B1; hereafter “BLASCHUK”).
BLASCHUK teaches the peptide KIDDTE (SEQ ID NO: 1931; col 41, lines 42-43), which is a peptide consisting of a peptide of instant (A2), wherein (A2) is a peptide of six consecutive amino acid residues of instant SEQ ID NO: 1, wherein the peptide includes instant SEQ ID NO: 3, and two amino acid substitutions thereof (underlined):
BLASHUK SEQ ID NO: 1931 KIDDTE
Instant SEQ ID NO: 3 DYDDTE
Therefore, SEQ ID NO: 1931 of BLASHCUK meets all of the structural requirements of instant claim 1.
MPEP § 2112.01(II) states: "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
In the instant case, the prior art teaches a peptide that meets all of the structural requirements of instant claim 1, part (A2) but is silent as to its function as an a-synuclein aggregation inhibitor. Because the prior art teaches a composition that meets all of the structural and physical limitations of the claim, the claimed property of a-synuclein aggregation inhibition is inherent to the prior art composition. The inventors have found a new property of an old composition and such a discovery does not constitute a new composition.
Therefore, BLASCHUK anticipates claim 1.
Regarding claim 3, SEQ ID NO: 1931 is a peptide wherein a peptide of (A1) that is SEQ ID NO: 3 is modified with two substitutions. Therefore, BLASCHUK anticipates claim 3.
Regarding claims 4 and 6-8, BLASHCUK teaches that the peptide KIDDTE is an example of a modulating agent (SEQ ID NO: 1931; col 41, lines 42-43). BLASHCUK teaches that modulating agents may be included in an effective amount in a pharmaceutical composition (col 75-76). Because the prior art teaches a composition that meets all of the structural and physical limitations of the claims, the claimed properties of a-synuclein aggregation inhibition, treating/preventing a disease caused by a-synuclein, treating/preventing Parkinson’s disease are inherent to the prior art composition. The inventors have found a new property of an old composition and such a discovery does not constitute a new composition.
Regarding claim 26, BLASHCUK teaches that the pharmaceutical composition may further comprise a pharmaceutically-acceptable carrier (col 75-76).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4-5, 7-8, and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/559,482 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because reference claims anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claim 6 recites an aggregation inhibitor having the sequence of SEQ ID NO: 3, which is identical to instant SEQ ID NO: 2. Because the reference claim recites a peptide of the structural and physical limitations of instant claims 1-2, the claimed property of a-synuclein aggregation inhibition is inherently met. Therefore, reference claim 6 anticipates instant claims 1-2.
Reference claim 10 recites a pharmaceutical composition for an amyloid b-disease caused by b-amyloid aggregation having the sequence of SEQ ID NO: 3, which is identical to instant SEQ ID NO: 2. Because the reference claim recites a composition of the structural and physical limitations of instant claims 4-5 and 7-8, the claimed properties of a-synuclein aggregation inhibition and disease treatment/prevention are inherently met. Therefore, reference claim 10 anticipates instant claims 4-5 and 7-8.
Regarding claim 26, it would have been obvious to include a carrier in the pharmaceutical composition of reference claim 10.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 8:30 am - 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CHRISTINA M MARCHETTI BRADLEY
Primary Examiner
Art Unit 1654
/CHRISTINA M MARCHETTI BRADLEY/ Primary Examiner, Art Unit 1654
