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 Group I, claims 16-32, in addition to the species of SEQ ID NO: 5, with a C-terminal CONH2 group, in D-amino acids, not linked to another peptide or substance, in the reply filed on 5/6/2026 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)).
Upon further search and examination, the species election was broadened to include SEQ ID NO: 1-4 and 6-7 in addition to the elected SEQ ID NO: 5.
Claim Status
Claims 16-35 are pending and new. Claims 33-35 are hereby withdrawn as non-elected inventions.
Priority
The instant application is the 371 national stage entry of PCT/EP2022/057456, filed 3/22/202, which claims priority to DE10 2021 107 061.9, filed 3/22/2021. The priority date of 3/22/2021 is acknowledged although it is noted that there is no translation of record.
Information Disclosure Statement
The IDS filed on 1/24/2025 is under consideration. Any strikethrough is owed to lack of a legible copy.
Drawings
The drawings are objected to because it is difficult to distinguish the types of treatments depicted in the non-bar graphs of Figures 1, 9, 13, 14, and 16-18 because all of the lines are in similar shades of gray. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
1. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specifically, see Figures 9, 14, and 16; the relevant SEQ ID NO’s can be included in the Figures themselves or their corresponding legends in the Specification.
2. Specific deficiency – The "Sequence Listing" has not been entered into the application because the required statement of no new matter is missing. See 37 CFR 1.825(a)(4) or 1.825(b)(5).
Required response – Applicant must provide:
A proper statement of no new matter.
Because the latest CRFE was filed after the initial filing date, a statement of no new matter is required, and one was not found in the Applicant Remarks filed on 4/3/2024.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see Pg 2, line 2). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms HiPrep and HiLoad (Pg 18, lines 24 and 29), LoBind (Pg 20, line 24), Agilent 1260 Infinity II System (Pg 21, line 19 and Pg 24, line 16), TopSpin (Pg 23, line 32), Eppendorf (Pg 23, line 32 and Pg 24, line 23), Lipofectamine (Pg 26, lines 31 and 38 and Pg 26, line 7), CellTiterGlo (Pg 26, lines 24 and 29), Fluostar (Pg 26, line 31), Triton X-100 (Pg 26, line 39 and Pg 27, line 32), Tween 20 (Pg 27, lines 3 and 5 and Pg 29 line 39), and NanoWizard (Pg 24, line 38; Pg 33, line 12; Pg 34, line 11), which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 17 is objected to because of the following informalities: line 1 reads “The peptide of claim 16, wherein peptide comprises an amino acid…”. Amend the claim such that line 1 reads “The peptide of claim 16, wherein the peptide comprises an amino acid…” (emphasis added). Appropriate correction is required.
Claim Interpretation
SEQ ID NO: 1-7 are being interpreted as consisting of only D-amino acids, as specified in the Sequence Listing.
Claim 16 recites “the peptide comprises an amino acid sequence...” (emphasis added). This claim is being interpreted as a peptide encompassing or containing the entirety of one of SEQ ID NO: 1-7 meets the limitation of the claim. Conversely, smaller fragments encompassed by SEQ ID NO: 1-7 (i.e., dipeptides) are being interpreted as not meeting the limitations of the claim. The “an amino acid” limitations of claims 17 and 21 are being interpreted in this same manner.
A “substance” as recited in claim 22 is being interpreted as a medicine or active ingredient (see instant Pg 13, lines 1-4).
Claims 30-32 each recite functional rather than structural elements of the instant invention. As such, the claims are being interpreted based upon the structural limitations (a peptide comprising SEQ ID NO: 1-7 or a homolog, fragment or portion thereof), where the functional limitations are properties endowed by the structure.
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.
Claim 20 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 20 recites that the peptide “consists substantially” of D-amino acids, wherein the instant specification defines “substantially consist of D-enantiomeric amino acids” as monomers formed to at least 50-100% D-enantiomeric amino acids (see instant Pg 12, lines 22-26). This limitation renders the claim indefinite as it is unclear whether the claim requires at least 50% D-amino acids, more than 50%, or 100%. Per the claim interpretation above, the peptides are being interpreted as consisting of 100% D-form amino acids.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 20 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 20 recites that the peptides consists substantially of D-amino acids. Based upon the claim interpretation, all of SEQ ID NO: 1-7 as recited in claim 16 are 100% D-amino acids. Thus, claim 20 does not further limit its parent claim 16. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 16-18, 20, 22, and 30-32 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 drawn to peptides comprising an amino acid sequence selected from SEQ ID NO: 1-7 and homologs, fragments, or portions thereof; additional claims further recite homologs having 80% sequence identity to one of SEQ ID NO: 1-7 (claim 17) as well as peptides, homologs, fragments, or portions thereof retaining certain binding characteristics and other functionalities (claims 30-32). The rejection is based on the limitation “homologs, fragments, or portions thereof”, which does not disclose sufficient structure-function relationship to meet the written description requirement.
The claims require peptides comprising SEQ ID NO: 1-7 or homologs, fragments, or portions thereof. The instant specification defines a homolog as an amino acid sequence that has at least 50-100% identity to one of the aforementioned SEQ ID NO’s (instant Pg 8, lines 12-16); in other words, a peptide that exhibits only 50% sequence identity to any one of SEQ ID NO: 1-7 would meet the limitations of the claims, or, as recited in claim 17, some homologs may have 80% identity to one of SEQ ID NO: 1-7. Further, a peptide comprising a fragment or portion of one of SEQ ID NO: 1-7 would include any peptide comprising at least a dipeptide derived from SEQ ID NO: 1-7. Thus, the breadth of the peptides that would meet the limitations of claim 16 based upon the “homologs, fragments, or portions thereof” limitation is substantial.
Subsequent dependent claims indicate that the breadth of peptides described above should retain certain functional characteristics. Per claims 30-32, said peptides, homologs, fragments, or portions thereof exhibit binding capabilities to α-synuclein peptide with a certain KD value, prevent formation of α-synuclein oligomers and/or aggregates, and detox existing oligomers and/or aggregates. However, the core structure or the residue(s) of SEQ ID NO: 1-7 that mediate these functionalities is unknown and untested in the instant application. The claims do not indicate any positional information (i.e., where alterations should occur in the sequence or where certain residues should be preserved) nor restrict the type amino acid mutation (i.e., it does not specify substituting one type of amino acid for another, adding amino acids, etc.). Without such information, it would be extremely difficult for one skilled in the art be able to derive homologs, fragments or portions of SEQ ID NO: 1-7 that that would retain said functionalities.
Regarding potential homologs of SEQ ID NO: 1-7, for example, the elected SEQ ID NO: 5 is 21 amino acids; sequences having at least 80% sequence identity would require 17 of the amino acids to be maintained (i.e. 5/21*100 = 81%) and would allow up to 4 amino acids (i.e. 21-5 = 4) to be substituted. Consequently, there are more than 5900 possible ways to select up to 4 residues from the 21 residues in the sequence that are free to be modified (i.e. x = n!/(r!(n-r)!)). Homologs with only 50% identity would necessarily result in an even larger number of potential variants, which would be in addition to any peptide comprising at least a single dipeptide from any of SEQ ID NO: 1-7 or a larger portion thereof. It should also be noted that Applicants have not disclosed any homologs, fragments, or portions thereof in the instant application.
Kelly et al. (US 20060058228, published 3/16/2006) discuss a phage display screen to identify peptides that distinguish between well-differentiated (HCT116) and poorly-differentiated (HT29) colon cancer cell lines. Analysis of the selected library resulted in the identification of a nine amino acid, disulfide-constrained peptide having a three amino acid (arg-pro-met, “RPM”) motif that specifically binds HT29 cells ([0032]). Substituting each of RPM with alanine significantly limited or abolished the ability of the peptide to compete with wild type RPM in a binding assay, indicating that these three residues alone accounted for the ability to bind to HT29 cells ([0034]). In contrast to this example, it is unknown which residues of SEQ ID NO: 1-7 must be preserved in order to retain their functionality. Thus, one cannot extrapolate homologs, fragments, or portions thereof that would similarly result in the same functional outcomes.
Consequently, it is unknown whether all variants encompassed within “homologs, fragments, or portions thereof” would retain the structural, chemical, and/or physical properties of SEQ ID NO: 1-7. Therefore, the instant specification does not provide adequate written description to possess the broad genus described above since the specification does not disclose a correlation between the necessary structure of the sequence and the claimed function to be maintained.
Improper Markush
Claim 18 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of a C-terminal modification or a cyclized peptide is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: they do not share a common structure.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Allowable Subject Matter
Peptides comprising or consisting of SEQ ID NO: 1-7, wherein the peptides are composed entirely of D-enantiomer amino acids, are free of the art. The closest art for each of the peptides is as follows:
SEQ ID NO: 243747 of US20040214272A1 (filed 4/28/2003) exhibits 48.5% sequence identity to SEQ ID NO: 1
SEQ ID NO: 853111 of US20070083334A1 (filed 5/31/2006) exhibits 54.7%, 57%, and 57.1% sequence identity to SEQ ID NO: 2, 4, and 6, respectively
SEQ ID NO: 164864 of US20070271630A1 (filed 2/24/2006) exhibits 57.9% sequence identity to SEQ ID NO: 3
SEQ ID NO: 771958 of US20070083334A1 (filed 5/31/2006) exhibits 42.1% sequence identity to SEQ ID NO: 5
SEQ ID NO: 86118 of US20110214205A1 (filed 2/26/2010) exhibits 49.2% sequence identity to SEQ ID NO: 7
Additionally, none of the above closest art peptides are in the D-enantiomeric form. Based on the low sequence identity between the instantly claimed peptides and the closest art, they are novel and non-obvious.
Further, claims 19, 21, and 23-29 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
In summary, claims 16-18, 20, 22, and 30-32 are rejected and claims 19, 21, and 23-29 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sara Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
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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
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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