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 .
Power of Attorney
The attorney who signed the most recent correspondence dated June 30, 2025, John G. Tutunjian, does not appear to be included in the power of attorney on record. In order to facilitate compact prosecution, including the use of interviews, Applicant is advised to file an updated power of attorney if needed.
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:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
The sequence disclosures are located in claims 101, 115, 116, 118, and 119 and pages 33-35 of the specification. The sequence RVPSTSSVPTKTSAISMLYL is presented as structure coordinates, which constitutes a specific enumeration of an amino acid sequence of four or more amino acids in length. This sequence is SEQ ID NO: 6612.
The sequence disclosures are located in claims 101, 115, 116, 118, and 119. The sequences SAIS, NAIS, and SPIS are specific enumerations of an amino acid sequence of four or more amino acids in length. These sequences are SEQ ID NOs: 6360, 6357, and 6364, respectively.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, 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.
Election/Restrictions
Applicant's election with traverse of Group I and “the species corresponding to SEQ ID NO: 102 (RVPSTSSVPTKTSAISMLYL)” in the reply filed on June 30, 2025, is acknowledged.
There is confusion regarding the election of species. The sequence listing has the following entry for SEQ ID NO: 102:
PNG
media_image1.png
400
623
media_image1.png
Greyscale
Therefore, the sequence associated with SEQ ID NO: 102 is not RVPSTSSVPTKTSAISMLYL. In addition, RVPSTSSVPTKTSAISMLYL is not a species of SEQ ID NO: 102 because it lacks the N-terminal cysteine. The sequence RVPSTSSVPTKTSAISMLYL does not appear to be one of the 6622 entries in the sequence listing. For the purposes of search and examination, SEQ ID NO: 102, as it is defined in the sequence listing, is being treated as the elected species.
The traversal is on the ground(s) that the method of use claim is not materially different in scope and that there is no burden to examine Groups I and II together. This is not found persuasive because the test for distinct inventions is whether the product as claimed can be used in a materially different process. In the instant case, the product could be used in methods of determining the three dimensional structure of the product, which is different than the tissue regeneration methods of Group II. Furthermore, the product and method claims raise different and complex issues under 35 U.S.C. 112 and 101.
Applicant traverses the election of species on the grounds that unity of invention exists. However, the restriction was issued under US practice. Applicant argues that the species in claims 103, 105, and 107 share a unifying structural feature of PEP1 and a common conformational constraint. This argument is not persuasive. First, the presence of PEP1 and length of less than 30 is not sufficient to yield a peptide with RMSD less than 2.45 Å relative to PEPREF, as evidenced by Table 6 in the specification. Therefore, PEP1 is not a substantial structural feature from which flows a common use. In addition, most peptides in the art are not reported with an RMSD relative to PEPREF. As a result, this feature creates a substantial search burden for each claimed species.
The requirement is still deemed proper and is therefore made FINAL.
Claims 115-119 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Elected species SEQ ID NO: 102 was searched. This species is free of the prior art but is subject to a non-statutory double patenting rejection.
The search was extended and prior art was found on SEQ ID NO: 6612, which is included in the scope of claims 101, 108-114, and 120-121, and 106 as being a peptide with up to 25 amino acids in length. The search was not extended further in accordance with MPEP § 803.02.
Claim Interpretation
BRI of claim 101 is a peptide or peptidomimetic that is up to 30 amino acids in length comprising PEP1, wherein PEP1 is selected from SAIS (SEQ ID NO: 6360), NAIS (SEQ ID NO: 6357), and SPIS (SEQ ID NO: 6364), wherein the RMSD value of the structure coordinates of said peptide or peptidomimetic with respect to PEPREF is 2.45 Å or less. The claim is given this construction in view of the definition of “peptide” on page 17, lines 30-36 of the specification, which states that the claim term “peptide” includes peptides and peptidomimetics. This construction is consistent with the language in lines 4-5 of the claim “said peptide or peptidomimetic”. The antecedent basis for “said peptidomimetic” is found in the definition of “peptide,” the term that appears earlier in the claim and which is defined in the specification to include peptidomimetic. The term “PEP1” is selected from “SAIS, NAIS, and SPIS” which are each limited to tetrapeptides consisting of the alpha-amino acids set forth in the respective sequences. That is, “SAIS” means serine-alanine-isoleucine-serine and excludes peptidomimetics of SAIS because S is given the plain meaning serine, A is given the plain meaning alanine, and I is given the plain meaning isoleucine, consistent with the specification and amino acid single letter code naming convention in the art. In this construction, the other up to 26 amino acids in the peptide may be peptidomimetics but the portion corresponding to PEP1 is not a peptidomimetic.
Claim Objections
Claim 101 is objected to because of the following informalities: the numbering of the amino acids in the structure coordinates includes an error at the alanine following serine 13. This alanine is misnumbered as amino acid 13 but should be 14. The amino acids C-terminal to this alanine are likewise misnumbered. Appropriate correction is required.
Claims 101 and 104 are objected to because of the following informalities: a period is missing at the end of the claims as required by MPEP § 608.01(m). Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 101-106, 108-109, 111-114, and 120-121 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.
I. Indefiniteness of “structural coordinates” in claim 101
In claim 101, the indefinite language is “the structural coordinates”. The language is indefinite because the structural coordinates of a peptide depend on the chemical structure (i.e. the amino acid sequence and backbone structure) of the peptide as well as the environment and conditions of the peptide and the presence or absence of binding partners. Because peptide structure is sensitive to environmental conditions such as pH, solvent, temperature, peptide concentration, and additive concentrations, as well as the presence of binding ligands, the structural coordinates of a single sequence can vary in response to these conditions. In addition, the structural coordinates are sensitive to constraints provided by the context of the full protein and its ligands, as evidenced by Zhao et al.1 Therefore, the term “structural coordinates” in claim 101 is a relative term which renders the claim indefinite. The term is relative because structural coordinates are dynamic and sensitive to environment. The term “structural coordinates” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Dependent claims 102-106, 108-109, 111-114, and 120-121 fail to remedy this issue and are likewise rejected.
II. Indefiniteness of “RMSD” in claim 101
In claim 1, the indefinite language is: “the RMSD value of the structure coordinates of said peptide or peptidomimetic with respect to PEPREF is 2.45 Å or less”. A method for determining the RMSD is presented in the specification beginning on page 30. The first step requires creating a 3-dimensional model of a peptide by obtaining a set of polypeptide 3D structure coordinates based on the alignment of the peptide sequence using BLAST, setting the database in the BLAST search to Protein Data Bank Proteins, and selecting the 3D structure coordinates of the ten structures having the highest sequence homology to the peptide of interest. New proteins continue to be deposited in the Protein Data Bank as new three-dimensional structures are obtained by researchers. Therefore, the results of this search will vary depending on when the search is conducted. In addition, the results could yield structures of single proteins as well as proteins in complex with ligands. The conformation of the peptide of interest will be influenced by its location within a larger protein as well as by a complex with other ligands, as evidenced by Zhao et al. As a result, the 3D structure coordinates for the peptide of interest from which the RMSD is calculated are a function of the BLAST search results at the time the search is conducted and will change depending on which proteins and which protein complexes the coordinates are based on. Therefore, the claimed RMSD as defined by the instant specification is a relative term, rendering the metes and bounds of claim 1 indefinite.
Dependent claims 102-106, 108-109, 111-114, and 120-121 fail to remedy this issue and are likewise rejected.
III. Indefiniteness of the list of alternatives in claim 102
Claim 102 recites “wherein the pair PEP9:PEP1 is selected from the group consisting of”. The list of alternatives that follows this phrase does not include the word “and” between the last and second to last option in the list. As a result, it is unclear what other alternatives are intended to be encompassed by the claim. See MPEP § 2173.05(h).
IV. Indefiniteness of “pair PEP9:PEP1” in claims 102 and 104
Claims 102 and 104 recite “the pair PEP9:PEP1”. The language is indefinite because the structural relationship between PEP9 and PEP1 in the peptide is unclear. BRI of this limitation includes multiple, plausible constructions: 1) PEP9 is required to be N-terminal to the PEP1 in the peptide; 2) PEP9 may be N- or C-terminal to PEP1; and 3) in both 1) and 2) PEP9 and PEP1 may be joined directly or separated by intervening amino acids. The confusion comes from the word “pair” which implies but does not explain a connectivity. In addition, the word pair is not conventionally used to define peptide sequences. The language is indefinite because it is not clear which construction is covered (e.g., because there is more than one reasonable interpretation of what construction is included in the claim). See MPEP § 2173.04.
The rejection could be overcome by amending claim 102 to: The peptide of claim 101 wherein when PEP1 is SAIS, the peptide further comprises PEP9, wherein PEP9 is selected from…, when PEP1 is NAIS, the peptide further comprises PEP9, wherein PEP9 is selected from…, and when PEP1 is SPIS, the peptide further comprises PEP9, wherein PEP9 is selected from….
The rejection could be overcome by amending claim 104 to: The peptide of claim 101 wherein PEP1 is SAIS and the peptide further comprises PEP9, wherein PEP9 is selected from…
V. Indefiniteness of the list of alternatives in claim 104
Claim 104 recites “wherein the pair PEP9:PEP1 is selected from the group consisting of”. The list of alternatives that follows this phrase does not include the word “and” between the last and second to last option in the list. In addition, the claim ends in a comma rather than a period. As a result, it is unclear what other alternatives are intended to be encompassed by the claim. See MPEP § 2173.05(h).
Claim Rejections - 35 USC § 112(a)
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 101-106, 108-109, 111-114, and 120-121 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.
Scope of the claims
The claims are drawn to peptides up to 30 amino acids in length, comprising a four-amino acid PEP1 selected from SAIS, NAIS, and SPIS, and having a RMSD of less than 2.45 Å relative to PEPREF.
Actual Reduction to Practice
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. 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.
In the instant case, several embodiments of the invention were reduced to practice: see Tables 4, 5 and 7 and Examples 4-17.
Species wherein PEP1 is SAIS (PEP3 and PEP1 underlined)
1 GSAGPSSVPTKMSAISMLYL
2 AAPASSSVPTRLSAISMLYL
3 STPPTSSVPTRLSAISMLYL
12 HVPKPSSAPTKLSAISMLYL
14 RNVQSRPTQVQLSAISMLYL
15 ASASPSSVSQDLSAISMLYL
18 TVPKPSSAPTQLSAISMLYL
19 AVPKASSAPTKLSAISMLYL
20 KVGKASSVPTKLSAISMLYL
21 GGGKASSVPTKLSAISMLYL
22 WWFWGSAGPSSTPTKMSAISMLYL
23 GTPGPHVTKPTSVPTKLSAISMLYL
26 GTPGPASSVPTKLSAISMLYL
27 GTPGPVPTGQSAISMLYL
28 GTPGPVPTEESAISMLYL
33 WWFWGKASKASSVPTKLSAISMLYL
34 GTPGPGSAGPSSTPTKMSAISMLYL
35 GTPGPAAPASSSVPARLSAISMLYL
95 VPTGQSAISMLYL
96 NDEGLESVPTEESAISMLYL
102 RVPSTSSVPTKTSAISMLYL
1071 RVPSTSSVPTELSAISVLYL
1144 RVPSTSSVPTGQSAISTLYL
1154 STPPTSSSRVQLSAISMLYL
1155 RVPSTSSTQVKMSAISMLYL
Species wherein PEP1 is NAIS (PEP3 and PEP1 underlined)
4 NDEGLESAPTEENAISVLYF
5 NDEGLESAPTGQNAISVLYF
11 RNVQSRPTQVQLNAISVLYF
17 NDEGLESVPTGQNAISVLYF
31 GTPGPNDEGLESAPTGQNAISVLYF
101 YVPKPSSAPTKLNAISVLYF
1074 RVPSTSSVPQQLNAISTLYF
1145 RVPSTSSAPTKMNAISMLYF
1158 AASKASSTPTDLNAISTLYF
1159 RVPSTSSTQVDLNAISVLYF
Species wherein PEP1 is SPIS (PEP3 and PEP1 underlined)
8 GSAGPSSVPTKMSPISVLYK
16 HVPKPSSVPTKLSPISVLYK
25 GTPGPVPTELSPISVLYK
29 GTPGPPTSVPTKLSPISVLYK
30 GTPGPPSSVPTKLSPISVLYK
32 WWFWGAAPASSSVPTRLSPISVLYK
43 RVPSTSSVPAKTSPISILYI
44 ASAAPSSVPAALSPISILYI
45 NDEGLESVPAEESPISILYI
46 VPAGQSPISILYI
47 NDEGLESVPAEESPISILYI
48 VPAEESPISILYI
49 GIPEPSSVPAKMSPISILYI
85 RNVQSRPVPTQLSPISVLYK
86 KIPKASSVPTELSPISVLYK
97 NDEGLESVPTEESPISILYI
98 VVVKSQPSRVHHSPISILYI
99 SSVKSQPSRVHHSPISILFI
100 RNVQSRPTQVQLSPISILFI
1076 RVPSTSSAPVEESPISTLYI
1077 RVPSTSSTQVRLSPISMLFI
1147 STPPTSSVPTELSPISTLYK
1162 STPPTSSAPVGQSPISMLYI
1163 KIPKASSTPTRLSPISMLFI
The specification states that these species have a RMSD of less than 2.45 Å relative to PEPREF and have the ability to induce tissue regeneration (Tables 4 and 5 and Examples 4-17). Each of these species comprises PEP1, with significant conservation at the four amino acids C-terminal to PEP1. Although these variations are allowed by the claims, they are not represented in the reduction to practice. In addition, the specification fails to include a reduction to practice of a peptidomimetic; all of the species are peptides.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
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 thereof.
i. Complete structure
As stated above, the complete structure of the peptides in Tables 4, 5 and 7 are disclosed.
ii. Partial structure:
The specification states that as a partial structure the peptides must comprise PEP1. Table 6 discloses numerous peptides that meet this requirement but that have an RMSD of greater than 2.45 Å and a less efficient ability to induce tissue regeneration (Table 6). Examination of the species from Table 6 shows that they have very similar sequences to the functional species in Tables 4 and 5.
For example, compare the following peptides from Table 6 comprising PEP1 of SAIS to the peptides from Tables 4, 5 and 7 comprising PEP1 of SAIS. Both sets of peptides comprise
[CS]-PEP3-XX-PEP1-xLY in many species.
KIPKPSSAPTELSAISMLC
KIPKPSSAPTELSAISMLYC
CIPKPSSAPTELSAISMLYL
CKIPKPSSAPTELSAISMLYL
AETLHTLGLSAPVIESAISDAI
MRTESTPTTASAISYECLWSPPSNEAAKLHFDS
CCAPTELSAISVLYFDDSSNVILKKYRNMVVRACGCR
CCAPTQLSAISVLYFDDSSNVILKKYRNMVVRACGCR
KPCCAPTQLSAISVLYFDDSSNVILKKYRNMVVRACGCR
KPCCAPTELSAISVLYFDDSSNVILKKYRNMVVRACGCR
Because the sequences with RMSD less than 2.45 Å and functional ability to induce tissue regeneration are so similar to the sequences with RMSD greater than 2.45 Å, it is unclear from the partial structure which additional elements are necessary to meet all of the claimed properties of the genus.
iii. Physical and/or chemical properties:
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 RMSD less than 2.45 Å and therefore do not describe which substitutions, deletions or additions could be made while preserving this conformation. Understanding the physical basis for having an RMSD less than 2.45 Å is critical to determining which of the sequences that meet the sequence requirements of the genus also meet this additional conformational requirement of the genus.
iv. Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification does not describe a general correlation between sequence and structural coordinates for the claimed genus. As a result, it is impossible to predict, based on the specification, how changing any position will affect the RMSD relative to PEPREF.
v. Method of making the claim invention
Solid state peptide synthesis and the cloning, recombinant expression and purification of proteins is well-known in the art. It is not disputed that one of ordinary skill in the art could isolate, albeit with route experimentation and optimization, a peptide of a given sequence provided that the sequence is known. Where the specification fails to provide description is in the structure of the peptide to make. 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 sequence requirements of the claims would also have a conformation with RMSD less than 2.45 Å. In other words, the specification does not describe which peptides to make.
Conclusion
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.
Claim Rejections – Improper Markush Grouping
Claims 101-114 and 120-121 are rejected on the basis that they contain 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 claims 101-114 and 120-121 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: there is no common amino acid sequence amongst all of the recited peptides. It is well-established in the art that the function and properties of a peptide are governed by the sequence of amino acid side chains, not merely by the presence of a peptide or peptidomimetic backbone. Therefore, a peptide or peptidomimetic backbone is not a substantial structural feature from which flows a common use.
Applicant asserts that the unifying structural feature is PEP1 of (S or N)-(A or P)-I-S and a RMSD of 2.45 or less relative to PEPREF. This argument is not persuasive. The presence of PEP1 and length of less than 30 is not sufficient to yield a peptide with RMSD less than 2.45 relative to PEPREF, as evidenced by Table 6 in the specification which shows numerous examples of peptides having PEP1 and an RMSD exceeding 2.45. Therefore, PEP1 is not a substantial structural feature from which flows a common property and/or function.
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.
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 101, 106, 108-109, 111, 113-114, and 121 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
I. Claims 101 and 106 are ineligible
Regarding claim 101, BRI of the claim includes the peptide KIPKACCVPTELSAISMLYL because the peptide is 20 amino acids in length (i.e. up to 30 amino acids in length), comprises a peptide with four amino acids consisting of SAIS, and has an RMSD value of its structure coordinates of 0 Å (i.e. 2.45 Å or less) with respect to PEPREF because it is identical to PEPREF. Regarding claim 106, BRI of the claim includes the peptide KIPKACCVPTELSAISMLYL because the peptide is 20 amino acids in length (i.e. up to 25 amino acids in length)].
Step 1: Claims 101 and 106 are to a composition of matter.
Step 2A, Prong 1: Claims 101 and 106 are directed to a product of nature, the peptide KIPKACCVPTELSAISMLYL. The closest counterpart to the nature-based product is human bone morphogenetic protein 2 (BMP-2). The claimed peptide corresponds to residues 73-92 of human BMP-2, as evidenced by Uniprot U3N491_Human. The claimed peptide has a different structural characteristic than the natural peptide, i.e., the natural peptide has covalent bonds on its ends that connect it to the rest of the protein whereas the claimed peptide lacks these bonds. However, the claimed peptide is otherwise structurally identical to the natural peptide, e.g., it has the same peptide backbone and amino acid sequence as residues 73-92 of BMP-2 in nature. This difference is not a marked difference in view of MPEP § 2106.04(c)(II)(C)(2) and the Supreme Court decision in Myriad. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977. In addition, the property of the claimed peptide, an RMSD of less than 2.45 Å, is innate to the peptide itself, and was not created or altered by the inventor. See Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, the claimed peptide is different, but not markedly different, from its naturally occurring counterpart (residues 73-92 of human BMP-2), and thus is a natural phenomenon exception.
Step 2A, Prong 2: The claims only recite the peptide, which is a natural phenomenon exception. Because there are no additional claim elements besides the judicial exception, the judicial exception is not integrated into a practical application (MPEP § 2106.04(d)(III)).
Step 2B: The claims only recites the peptide, which is a natural phenomenon exception. Because there are no additional claim elements besides the judicial exception, the claim does not amount to significantly more than the judicial exception (MPEP § 2106.05).
Therefore, claims 101 and 106 are patent ineligible.
II. Claims 108, 111, 113-114, and 121 are ineligible
Regarding claim 108, BRI of the claim includes a functionalized biomaterial comprising a peptide and a biomaterial. BRI of the peptide includes KIPKACCVPTELSAISMLYL because the peptide is 20 amino acids in length (i.e. up to 30 amino acids in length), comprises a peptide with four amino acids consisting of SAIS, and has an RMSD value of its structure coordinates of 0 Å (i.e. 2.45 Å or less) with respect to PEPREF because it is identical to PEPREF. BRI of the biomaterial includes collagen, as evidence by dependent claims 114 and 121. BRI of claim 113 also includes collagen because collagen is polymeric (i.e. a polymer of amino acids). Regarding claim 111, BRI of the claim includes a composition intended for medical use comprising a peptide, a biomaterial and medically-acceptable carrier. BRI of the carrier includes water.
Step 1: Claims 108, 111, 113-114, and 121 are to a composition of matter.
Step 2A, Prong 1: Claims 108, 113-114, and 121 are directed to a product of nature, the peptide KIPKACCVPTELSAISMLYL and a biomaterial, which is a nature-based product such as collagen. Claim 111 is directed to the same plus the product of nature water. Because the peptide and collagen (and water) as claimed are not found together in nature, the closest counterpart to the nature-based products is residues 73-92 of human BMP-2 and collagen (and water). As determined in the analysis of claims 101 and 106 above, the claimed peptide is different, but not markedly different from residues 73-92 of human BMP-2. There is no evidence on record that mixing the claimed peptide with collagen (or collagen plus water) changes the structure, function, or other properties of either the peptide or collagen (or water) in a marked way. Thus, for at least one embodiment of the claim within the BRI (e.g. wherein the biomaterial is collagen and the carrier is water), the claimed mixture as whole does not display markedly different characteristics compared to the naturally-occurring counterparts. Instead, the peptide and collagen have the same characteristics in the mixture as the individual components, the same chemical structure and for the peptide, the same property of having an RMSD of 2.45 Å or less compared to PEPREF, and for the collagen, the same function of being a structural protein (and for water the same function of being a solvent). See Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948). Accordingly, each component, the peptide and the collagen (and water), is a natural phenomenon exception.
Step 2A, Prong 2: The claim only recites the peptide and the collagen (and water), which are natural phenomenon exceptions. Because there are no additional claim elements besides the judicial exceptions, the judicial exceptions are not integrated into a practical application (MPEP § 2106.04(d)(III)). In addition, because the preamble “functionalized” (or “medical”) does not actually provide a specific use, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception (MPEP § 2106.04(d)(2)).
Step 2B: Because the preamble “functionalized” (or “medical”) does not actually provide a specific use, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot be significantly more than the judicial exception (MPEP § 2106.04(d)(2)).
Therefore, claims 108, 111, 113-114, and 121 are patent ineligible.
III. Claim 109 is ineligible
Regarding claim 109, BRI of the claim includes a composition intended for medical use comprising a peptide and medically-acceptable carrier. BRI of the peptide includes KIPKACCVPTELSAISMLYL because the peptide is 20 amino acids in length (i.e. up to 30 amino acids in length), comprises a peptide with four amino acids consisting of SAIS, and has an RMSD value of its structure coordinates of 0 Å (i.e. 2.45 Å or less) with respect to PEPREF because it is identical to PEPREF. BRI of the carrier includes water.
Step 1: Claim 109 is to a composition of matter.
Step 2A, Prong 1: Claim 109 is directed to a product of nature, the peptide KIPKACCVPTELSAISMLYL and the medically acceptable carrier, which may be a nature-based product such as water. Because the peptide and water as claimed are not found together in nature, the closest counterpart to the nature-based products is residues 73-92 of human BMP-2 and water. As determined in the analysis of claims 101 and 106 above, the claimed peptide is different, but not markedly different from residues 73-92 of human BMP-2. There is no evidence on record that mixing the claimed peptide with water changes the structure, function, or other properties of either the peptide or water in a marked way. Thus, for at least one embodiment of the claim within the BRI (e.g. wherein the carrier is water), the claimed mixture as whole does not display markedly different characteristics compared to the naturally-occurring counterparts. Instead, the peptide and water have the same characteristics in the mixture as the individual components, the same chemical structure and for the peptide, the same property of having an RMSD of 2.45 Å or less compared to PEPREF, and for the water, the same function of being a solvent. See Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948). Accordingly, each component, the peptide and the carrier, is a natural phenomenon exception.
Step 2A, Prong 2: The claim only recites the peptide and the carrier, which are natural phenomenon exceptions. Because there are no additional claim elements besides the judicial exceptions, the judicial exceptions are not integrated into a practical application (MPEP § 2106.04(d)(III)). In addition, because the limitation “medical composition” does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration (MPEP § 2106.04(d)(2)).
Step 2B: Prior to applicant’s invention and at the time of filing the application, using water as a carrier for a peptide was well-understood, routine, and conventional, as evidenced by Global Pharma Tek2. Because mixing the peptide with a carrier at this high level of generality does not meaningfully limit the claim, the claim does not amount to significantly more than the judicial exception (MPEP § 2106.05). In addition, because the limitation “medical composition” does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot be significantly more than the judicial exception (MPEP § 2106.04(d)(2)).
Therefore, claim 109 is patent ineligible.
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 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.
I. Anticipation over Zouani et al.
Claims 101, 106, 108-109, and 111-113 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zouani et al. (Differentiation of pre-osteoblast cells on poly(ethylene terephthalate) grafted with RGD and/or BMPs mimetic peptides. Biomaterials 31 (2010) 8245-8253).
Zouani et al. teach three peptides in Figure 1e, KIPKACCVPTELSAISMLYL, TVPKPSSAPTQLNAISTLYF, and KVGKASSVPTKLSPISILYK, and report the RMSD value of the structure coordinates of each peptide relative to PEPREF.3
BRI of claim 101 includes each of these peptides:
KIPKACCVPTELSAISMLYL is 20 amino acids in length, comprises SAIS as PEP1, and has an RMSD value of 0 Å with respect to PEPREF;
TVPKPSSAPTQLNAISTLYF, is 20 amino acids in length, comprises NAIS as PEP1, and has an RMSD value of 1.88 Å with respect to PEPREF; and
KVGKASSVPTKLSPISILYK, is 20 amino acids in length, comprises SPIS as PEP1, and has an RMSD value of 1.94 Å with respect to PEPREF.
The requirement that the peptides comprise PEPI wherein PEP1 is SAIS, NAIS, or SPIS is met.
MPEP § 2131.03(I) states: "[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In re Petering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)).
In the instant case, the prior art peptide length 20 falls within the claimed range up to 30, and the prior art RMSD values 0, 1.88 and 1.94 fall within the claimed range less than 2.45. Therefore, the claimed ranges are anticipated by the prior art species.
Therefore, Zouani et al. anticipate claim 101.
With respect to claim 106, the prior art peptide length 20 falls within the claimed range up to 25.
With respect to claims 108 and 113, Zouani et al. teach PET surface preparation and covalent grafting of the peptides onto the PET surface (§ 2.2.2): “materials were modified in order to create COOH functions on PET surfaces. Next, PET-COOH samples were immersed in a solution of EDC (0.2 M) þ NHS (0.1 M) in MES buffer (0.1 M in MilliQ water) and then rinsed in MilliQ water (50 ml during 30 min). Same protocol was applied for each surface. Finally, immobilization of mimetic peptides was achieved in a solution of mimetic peptides (GRGDSPC and/or BMPs mimetic peptides)/PBS.”
BRI of claim 108 includes the peptides taught by Zouani et al. covalently linked to the polymer surfaces. The peptides meet the requirements of claim 101 for the reasons above. BRI of biomaterials include the polymer surfaces, as evidenced by dependent claim 113.
With respect to claims 109 and 111, Zouani et al. teach that the PET grafted with BMP-2 peptides are in water (§ 2.2.2). BRI of medically-acceptable carrier includes water.
With respect to claim 112, Zouani et al. is silent with respect to the stiffness of the biomaterial utilized. Burden is shifted to Applicant to determine if the biomaterials in the reference possess the property of stiffness recited in the claim.
II. Anticipation over Park et al.
Claims 101, 106, 108-109, 111-114, and 120-121 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Park et al. (US 7,897,163 B2).
Park et al. teach a bone graft material and a scaffold, on the surfaces of which a cell adhesion-inducing peptide and/or tissue growth factor-derived peptide having pharmacological activity are immobilized so that the bone graft material and the scaffold have pharmacological activity, whereby their efficiency for the regeneration of bone tissue or other tissues can be increased (col 2, lines 40-46).
Park et al. teach that the peptide is the amino acid sequence at positions 73-92 of BMP-2 (SEQ ID NO: 8), which is KIPKACCVPTELSAISMLYL.
BRI of claim 101 includes SEQ ID NO: 8 taught by Park et al.:
the peptide KIPKACCVPTELSAISMLYL is 20 amino acids in length, comprises SAIS as PEP1, and has an RMSD value of 0 Å with respect to PEPREF because it is identical in sequence and length to PEPREF.
The requirement that the peptides comprise PEPI wherein PEP1 is SAIS is met.
MPEP § 2131.03(I) states: "[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In re Petering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)).
In the instant case, the prior art peptide length 20 falls within the claimed range up to 30, and the prior art RMSD value 0 falls within the claimed range less than 2.45. Therefore, the claimed ranges are anticipated by the prior art species.
Therefore, Park et al. anticipate claim 101.
With respect to claim 106, the prior art peptide length 20 falls within the claimed range up to 25.
With respect to claim 108, Park et al. teach in Example 5: “For use as tissue growth factor-derived peptides in this Example, peptides were chemically synthesized by adding a CGG spacer to the N-terminal end of each of amino acid sequences of SEQ ID NO: 3 and SEQ ID NOS: 6-9, which contain the cell adhesion and activation domain of bone morphogenetic protein BMP-2 so as to introduce cysteine into the N-terminal end. Bovine bone-derived bone mineral particles were washed with ethanol under reduced pressure and then left to stand in a vacuum oven at 100° C for 20 hours so as to remove impurities from the surface. The surface of the bone mineral particles was treated with a solution of 3-aminopropyl ethoxysilane (APTES) in hexane, followed by washing. This resulted in the formation of amine residues on the surface of particles, to which sulfo-SMCC as a crosslinker was then added at a concentration of 5 mg/ml. This mixture was stirred for 2 hours so as to introduce functional groups onto the surface of the bone graft material. After 2 hours of reaction at ambient temperature, the bone graft material was washed, and allowed to react with a solution of 10 mg of the peptides dissolved in 100 ml of phosphate buffer for 24 hours, followed by washing. This yielded the bone mineral particles with the peptides immobilized thereon.”
BRI of claim 108 includes the SEQ ID NO: 8 modified with CGG at the N-terminus and immobilized on bone mineral particles taught by Park et al. The peptide meets the requirements of claim 101 for the reasons above. BRI of biomaterials include the bone mineral particles. Therefore, claim 108 is anticipated.
Regarding claims 109 and 111, BRI of medically acceptable carrier includes phosphate buffer taught by Park et al. in Example 5. BRI of “medical composition” includes the tissue engineering contemplated by Park et al. (see claims).
With respect to claim 112, Park et al. is silent with respect to the stiffness of the biomaterial utilized. Burden is shifted to Applicant to determine if the biomaterials in the reference possess the property of stiffness recited in the claim.
Regarding claims 113-114 and 120, Park et al. teach that the biomaterial may be organism-derived bone mineral powders and porous blocks originated from autogeneous bone, bovine bone and porcine bone, synthetic hydroxyapatite powders and porous blocks, tricalcium phosphate powders and porous blocks, monocalcium phosphate powders and porous blocks, bone graft materials made of silicon dioxide (silica), bone-packing graft materials made of a mixture of silica and polymer, fine particles and porous scaffolds made of biocompatible polymers, including chitosan and polylactic acid, and titanium and three-dimensional scaffolds (col 4, lines 38-56).
Regarding claims 114 and 121, the bone materials taught by Park et al. contain Type I collagen, as evidenced by Amirrah et al. 4
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 101-112 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,578,110. Although the claims at issue are not identical, they are not patentably distinct from each other because