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 .
Status of the Claims
Claims 1-11 were originally filed March 9, 2023.
The preliminary amendment received March 9, 2023 amended claims 3-5, 7, 8, and 11 and canceled claim 10.
Claims 1-9 and 11 are currently pending.
Claims 1, 2, and 5-8 are currently under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-9) in the reply filed on December 3, 2025 is acknowledged.
Claim 11 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 3, 2025.
Applicant’s election without traverse of SEQ ID NO: 1, intramolecular disulfide bond connecting X and Y, SEQ ID NO: 5, acylation, amidation, and SEQ ID NO: 10 as the species in the reply filed on December 3, 2025 is acknowledged.
Please note: the election of SEQ ID NO: 10 (Ac-(D-Cys)(D-Ala)(D-Arg)(D-Arg)(D-Arg)(D-Ala)(D-Arg)-NH2) wherein Cys is linked to SEQ ID NO: 5 via a disulfide bond does not correlate with the election of SEQ ID NO: 1 (Ac-CysAlaArgArgArg(D-Ala)Arg). The election of SEQ ID NO: 1 is considered controlling.
Claims 3, 4, and 9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 3, 2025.
Please note: claim 3 is withdrawn because the Markush group for Xaa2 does not contain Aib (a-aminoisobutyric acid; SEQ ID NO: 5 - TyrAibPheGlyGlyCys). Xaa2 contains 2-aminoisobutyric acid (AiB) as a member.
Please note: claim 4 is withdrawn because a cyclic peptide was not elected.
Please note: claim 9 is withdrawn because each amino acid in Y (top sequence) is in the D form. Elected SEQ ID NO: 1 is (Ac-CysAlaArgArgArg(D-Ala)Arg).
Potential Rejoinder
Applicant elected claims directed to a product. If a product claim is subsequently found allowable, withdrawn process claims that depend from or otherwise include all the limitations of the allowable product claim will be rejoined in accordance with the provisions of MPEP § 821.04. Process claims that depend from or otherwise include all the limitations of the patentable product will be entered as a matter of right if the amendment is presented prior to final rejection or allowance, whichever is earlier. Amendments submitted after final rejection are governed by 37 CFR 1.116; amendments submitted after allowance are governed by 37 CFR 1.312.
In the event of rejoinder, the requirement for restriction between the product claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all the criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103, and 112. Until an elected product claim is found allowable, an otherwise proper restriction requirement between product claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowed product claim will not be rejoined. See “Guidance on Treatment of Product and Process Claims in light of In re Ochiai, In re Brouwer and 35 U.S.C. § 103(b),” 1184 O.G. 86 (March 26, 1996). Additionally, in order to retain the right to rejoinder in accordance with the above policy, applicant is advised that the process claims should be amended during prosecution either to maintain dependency on the product claims or to otherwise include the limitations of the product claims. Failure to do so may result in a loss of the right to a rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Priority
The present application is a 371 (National Stage) of PCT/CN2021/088266 filed April 20, 2021 which claims foreign priority to China 202010946404.5 filed September 10, 2020.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome any rejection of record because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on March 20, 2023 and September 13, 2024 are being considered by the examiner.
Please note: only English language portions of the references were considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE 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).
See page 18, lines 24 and 25 and paragraphs 191, 192, 200, 202, 204, 205, 207, 210, 211, 213, and 214.
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.
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located at page 10, lines 24 and 25 (i.e. (GlySer)2, (GlySer)3, SGGSGGS). See n = 2 or 3.
See claim 7.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Specification
Throughout the specification, 2-aminoisobutyric acid (AiB) is referred to. However, SEQ ID NOs: 5 and 14 contain Aib (a-aminoisobutyric acid). It is unclear if this is in error or not. No new matter may be added.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 2 is objected to because of the following informalities: utilization of formula (IIa) and formula (IIb) twice is unnecessary. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: a conjunction should be present between “formula (IIa)” and “formula (IIb)”. See line 3. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: “set forth in formula (IIa) or formula (IIb)”; “formula (IIa)”; and “formula (IIb)” should be deleted. The claim correctly labels the variable sequences as amino acid sequences. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: “peptide chain” should read “peptide sequence”. Appropriate correction is required.
Claim 5 is objected to because of the following informalities: “modification” at line 3 is redundant and unnecessary. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: the repetition of “wherein ID is an intramolecular disulfide bond or a linker formed between X and Y” from claim 1 is unnecessary. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: the numbers (e.g. “(1)”, “(2)”) should be removed as the numbers are unnecessary. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: the numbers (e.g. “(1)”, “(2)”) should be removed as the numbers are unnecessary. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: the inclusion of the N- and C-terminus is unnecessary and should be removed (e.g. H2N and OH for SEQ ID NOs: 2-6, 12, and 13). Anyone of skill in the art would know what the structure of the N- and C-terminus is. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: “L” should be removed because it could be interpreted as L/Leu/leucine. Anyone of skill in the art would know that the amino acid is in the L form. It is also unclear why only some amino acids are designated as L. See SEQ ID NOs: 2, 3, 5, 6, and 12-16. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: for clarity regarding “D”, the amino acids in D form should be written as follows: (D-Tyr). For example SEQ ID NO: 3 should be written as (D-Tyr)Cys(D-Phe)GlyGly. D may be interpreted as D/Asp/aspartic acid as presently found in the claims. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: “peptide chain” should read “peptide sequence”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: utilization of SEQ ID NO: 2-6 and 12-18 twice is redundant. Appropriate correction is required.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3. Any claim requiring a specific percent identity, necessarily requires at least the recited percent identity.
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.
Claims 1, 2, and 5-8 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. This is a written description rejection.
With regard to the written description requirement, the attention of the Applicant is directed to The Court of Appeals for the Federal Circuit which held that a “written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1405 (1997), quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original) [The claims at issue in University of California v. Eli Lilly defined the invention by function of the claimed DNA (encoding insulin)] (the case is referred to herein as “Lilly”).
Additionally, it is noted that written description is legally distinct from enablement: “Although the two concepts are entwined, they are distinct and each is evaluated under separate legal criteria. The written description requirement, a question of fact, ensures that the inventor conveys to others that he or she had possession of the claimed invention; whereas, the enablement requirement, a question of law, ensures that the inventor conveys to others how to make and use the claimed invention.” See 1242 OG 169 (January 30, 2001) citing University of California v. Eli Lilly & Co.
Although directed to DNA compounds, this Eli Lilly holding would be deemed to be applicable to any compound or a generic of compounds; which requires a representative sample of compounds and/or a showing of sufficient identifying characteristics; to demonstrate possession of the compound or generic(s). In this regard, applicant is further referred to University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997); “Guidelines for Examination of Patent Applications Under the 35 USC 112, first paragraph, ‘Written Description’ Requirement” published in 1242 OG 168-178 (January 30, 2001); and Univ. Of Rochester v G. D. Searle and Co. 249 F. Supp. 2d 216 (W.D.N.Y. 2003) affirmed by the CAFC on February 13, 2004 (03-1304) publication pending.
Additionally, Lilly sets forth a two part test for written description:
A description of a genus of cDNA’s may be achieved by means of a recitation of:
a representative number of cDNA’s, defined by nucleotide sequence, falling within the scope of the genus OR of a recitation of structural features common to the members of the genus.
See Regents of the University of California v. Eli Lilly & Co. 119 F.3d 1559 (Fed. Cir. 1997) at 1569.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Additionally, Cf. University of Rochester v G.D. Searle & Co., Inc., Monsanto Company, Pharmacia Corporation, and Pfizer Inc., No. 03-1304, 2004 WL 260813 (Fed. Cir., Feb. 13, 2004) held that:
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
In the present instance, the specification discloses only limited examples that are not representative of the claimed genus of a “calcium-sensing receptor agonist” or an “osteogenic growth peptide-like peptide or a stimulator of bone marrow mesenchymal stem cells”; nor do the claims recite sufficient structural features which are common to members of the genus sufficient to demonstrate possession of the genus. The instant claims define a Y as a “calcium-sensing receptor agonist” and X as an “osteogenic growth peptide-like peptide or a stimulator of bone marrow mesenchymal stem cells”. Y as presently claimed in independent claim 1 can be any calcium-sensing receptor agonist including small molecules, RNAi, polypeptides, etc. While the preamble requires a polypeptide compound, the entire structure of Y-ID-X or X-ID-Y does not have to be a polypeptide (e.g. the “compound” could contain other structures as long as one of the structures is a polypeptide). X as claimed in independent claim 1 is either an “osteogenic growth peptide-like peptide or a stimulator of bone marrow mesenchymal stem cells”. The stimulator of bone marrow mesenchymal stem cells can be anything including small molecules, polynucleotides, polypeptides, etc. While the preamble requires a polypeptide compound, the entire structure of Y-ID-X or X-ID-Y does not have to be a polypeptide (e.g. the “compound” could contain other structures as long as one of the structures is a polypeptide). The “osteogenic growth peptide-like peptide” does require a peptide. The claimed “Y” and “X” are only defined by functional properties (e.g. “calcium-sensing receptor agonist”, an “osteogenic growth peptide-like peptide, or a stimulator of bone marrow mesenchymal stem cells”) except that the “osteogenic growth peptide-like peptide” is a peptide. The CAFC held that a functional definition is insufficient to adequately describe a product, therefore, an adequate written description not based on a functional definition is necessary.
The Examiner further notes the present claims stated by Applicant are broader in scope that those that were held to be impermissible in Lilly because, unlike Lilly, Applicants’ claims encompass a vast number of “calcium-sensing receptor agonist” and an “osteogenic growth peptide-like peptide or a stimulator of bone marrow mesenchymal stem cells”. Here, the Applicant claims “Y” and “X” by function only except that the “osteogenic growth peptide-like peptide” is a peptide. The scope of these claims include a vast number of sequences and/or structures because the specification and claims do not place any limit on the number of components (e.g. common core for function, length, etc.) or the type of components (e.g. chemical structure, polynucleotide, polypeptide). Furthermore, the specification and claims do not place any limit on the number of components or the types of components. Therefore, Applicant is using an inadequately described “Y” and “X” to inadequately describe the claimed “polypeptide compound”. Consequently, there is no teaching that would allow a person of skill in the art to determine a priori that the Applicant was in possession of the full scope of the claimed invention at the time of filing because there is no common structural attributes that can link together all of the claimed “Y” or “X”.
While the general knowledge and level of skill in the art for making polypeptide compounds is high, this knowledge and level of skill does not supplement the omitted description because specific, not general, guidance is needed for “Y” and “X”. Since the disclosure fails to describe the common attributes or characteristics that identify all of the members of the genus or even a substantial portion thereof, and because the genus is vast and highly variant (e.g. small chemical, polynucleotide, polypeptides), the limited examples in the specification (please refer to SEQ ID NOs: 1, 7-11, and 19-27 for “Y” and SEQ ID NOs: 2-18 for “X”) are insufficient to teach the entire genus.
For “Y”, the originally filed specification teaches SEQ ID NOs: 1, 7-11, and 21-27 which are all the same sequence (Ac-CARRRAR-NH2) with or without various D amino acids.
“Y” is also CRKKRAR (SEQ ID NO: 19).
“Y” is also CRRARAR (SEQ ID NO: 20).
Thus, the originally filed specification teaches three peptide sequences for “Y” with a common core of CX1X2X3RAR wherein X1 is A or R, X2 is R or K, and X3 is R, K, or A.
For “X”, the originally filed specification teaches SEQ ID NOs: 2-4 which are all YCFGG with or without D amino acids.
“X” is also YAibFGGC which is linear (SEQ ID NO: 5) or cyclic (SEQ ID NO: 14).
“X” is also YRFGGC which is linear (SEQ ID NO: 6) or cyclic (SEQ ID NO: 15).
“X” is also YHYGGC (SEQ ID NO: 12).
“X” is also YPFGGC (SEQ ID NO: 13).
“X” is also YGFGGC which is linear (SEQ ID NO: 16) or cyclic (SEQ ID NO: 17) and CGGFGY (SEQ ID NO: 18) which is the reverse of SEQ ID NO: 16.
Thus, the originally filed specification teaches six peptide sequences for “X” with a common core of YX1FGGX2 wherein X1 is C, Aib, R, H, G, or P and X2 is C or absent.
The specification discloses only limited examples that are not representative of the claimed genus of a “Y” or “X”; nor do the claims recite sufficient structural features which are common to members of the genus sufficient to demonstrate possession of the genus. Therefore, the teachings in the specification are general teachings relating without guidance as to the individual components of the product. In addition, there are numerous polypeptides, small molecules, and polynucleotides that could be employed in the invention with little direction or guidance for one of skill in the art to practice the claimed invention. The expedient statements in the specification do not relate to an adequate disclosure or how to make and use the claimed invention. Consequently, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to adequately describe the vast genus. Thus, Applicant does not appear to be in possession of the claimed genus.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, and 5-8 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if “having a structure represent by” is open, closed, etc. (see claim 1). It is also unclear if “set forth in” is open, closed, etc. (see claim 2).
Claim 2 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.
Regarding claim 2, the phrase "preferable" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 2 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if applicants are presuming that one of skill in the art would interpret the amino acids as both in the L and D form without explicitly stating so in the claims (see lines 6-12 and lines 15-24). One of skill in the art would presume the amino acids are in the L form unless explicitly stated as being in the D form in the claim.
Claim 5 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 5 recites the limitation "the chemical modification" in lines 2-4 (twice). There is insufficient antecedent basis for this limitation in the claim.
Claim 6 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 6 recites the broad recitation “alkylation”, and the claim also recites “C1-6 alkylation or aralkylation” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 7 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 7 recites the broad recitation “wherein ID is an intramolecular disulfide bond or a linker formed between X and Y”, and the claim also recites “wherein the intramolecular disulfide bond is formed between cysteine, …”, “the linker is selected from the group consisting of an amino-substituted C1-8 alkyl acid…” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 7 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 7 recites the broad recitation “the linker is selected from the group consisting of…a peptide fragment consisting of 1-10 amino acids”, and the claim also recites “the amino acid in the peptide fragment is selected from the group consisting of proline, arginine…” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 7 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 7 recites the broad recitation “the amino acid in the peptide fragment is selected from the group consisting of proline, arginine…”, and the claim also recites “the linker is selected from the group consisting of…(Gly-Ser)n wherein n is…” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 7 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear how the linker can be nothing (i.e. (Gly-Ser)n where n = 0). Is this simply a fusion polypeptide where the amino acids are directly linked? One of skill in the art would expect a linker to be more than a normal amino acid linkage.
Claim 8 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if the transitional phrase provides clarification for the sequences in the wherein clause or not. The transitional phrase should be directly linked to the sequences.
Please note: due to the myriad of objections and 35 USC 112 issues with the claims, applicant is respectfully requested to carefully review the claims for any additional issues. Applicant is also respectfully requested to extrapolate the above objections and 35 USC 112 rejections to the withdrawn claims. The claims are unnecessarily convoluted and are required to be amended.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 2, 5, 6, and 7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Karim et al. WO 2011/014707 published February 3, 2011 (provided with the Restriction Requirement mailed on October 8, 2025).
For present claims 1, 2, 5, 6, and 7, Karim et al. teach polypeptides which modulate PTH in order to modulate calcium levels (i.e. peptides which are “calcium-sensing receptor agonist” and “osteogenic growth peptide-like peptide or stimulator of bone marrow mesenchymal stem cells”) including CARRRAR (SEQ ID NOs: 2, 3, 12, 26, 146; present SEQ ID NOs: 1, 7-11, and 21-27) or CRRARAR (SEQ ID NO: 25; present SEQ ID NO: 20) and variable peptide sequences which encompass CRKKRAR (present SEQ ID NO: 19) wherein all L amino acids are utilized, all D amino acids are utilized, or a mixture of L and D amino acids are utilized; the N- and/or C-terminus is modified wherein the modification is acetylation, amidation, PEGylation, benzoyl, alkylation, sulfonylation, sulfonamide; a peptide with a cysteine/thiol-containing group are linked to another peptide with a cysteine/thiol-containing group to form disulfide bonds wherein the peptides with cysteine/thiol-containing groups are the same or different; thiol-containing group may also be homocysteine (please refer to the entire specification particularly the abstract; paragraphs 3-22, 25-33, 41, 43-49, 51-53, 60, 62-64, 71, 73, 74, 81, 89-91, 93-99, 102, 103, 107-109, 111, 116, 127-144, 153; Tables).
Therefore, the teachings of Karim et al. anticipate the presently claimed polypeptide.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 2, and 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Karim et al. WO 2011/014707 published February 3, 2011 (provided with the Restriction Requirement mailed on October 8, 2025) and Newcomb et al. U.S. Patent 6,653,460 issued November 25, 2003.
For present claims 1, 2, and 5-8, Karim et al. teach polypeptides which modulate PTH in order to modulate calcium levels (i.e. peptides which are “calcium-sensing receptor agonist” and “osteogenic growth peptide-like peptide or stimulator of bone marrow mesenchymal stem cells”) including CARRRAR (SEQ ID NOs: 2, 3, 12, 26, 146; present SEQ ID NOs: 1, 7-11, and 21-27) or CRRARAR (SEQ ID NO: 25; present SEQ ID NO: 20) and variable peptide sequences which encompass CRKKRAR (present SEQ ID NO: 19; K is a conservative amino acid substitution for R also) wherein all L amino acids are utilized, all D amino acids are utilized, or a mixture of L and D amino acids are utilized; the N- and/or C-terminus is modified wherein the modification is acetylation, amidation, PEGylation, benzoyl, alkylation, sulfonylation, sulfonamide; a peptide with a cysteine/thiol-containing group are linked to another peptide with a cysteine/thiol-containing group to form disulfide bonds wherein the peptides with cysteine/thiol-containing groups are the same or different (i.e. both are “calcium-sensing receptor agonist” and/or “osteogenic growth peptide-like peptide or stimulator of bone marrow mesenchymal stem cells”); thiol-containing group may also be homocysteine (please refer to the entire specification particularly the abstract; paragraphs 3-22, 25-33, 41, 43-49, 51-53, 60, 62-64, 71, 73, 74, 81, 89-91, 93-99, 102, 103, 107-109, 111, 116, 127-144, 153; Tables).
For present claims 1, 2, and 5-8, Newcomb et al. teach peptides that alter class E voltage-gated calcium channels including SEQ ID NO: 19 (CRYMFGGC; present SEQ ID NO: 5 YAibFGGC; P and G are conservative amino acid substitutions for M – present SEQ ID NOs: 13 and 16-18) with disulfide bridging patterns and N-terminal acetylation (please refer to the entire specification particularly the abstract; columns 1-5, 12, 13, 18, 24).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements (e.g. various calcium modulating peptides) as claimed by known methods (i.e. making dimers via disulfide linkage of cysteine residues) with no change in the respective function (e.g. function of the peptides is unchanged) and the combination would have yielded predictable results (e.g. multiple calcium modulating peptides) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of a peptide which modulates calcium; methionine) for another (i.e. species of a peptide - CRYMFGGC - which modulates calcium; conservative amino acid substitution of proline or glycine) would have yielded predictable results (i.e. modulation of calcium) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because a particular known technique (i.e. making peptide dimers via linking cysteine residues) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Claims 1, 2, and 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Karim et al. WO 2011/014707 published February 3, 2011 (provided with the Restriction Requirement mailed on October 8, 2025); Newcomb et al. U.S. Patent 6,653,460 issued November 25, 2003; and Tran et al., 2006, Designing amino acid residues with single-conformations, Protein Engineering, Design & Selection, 19(9): 401-408.
For present claims 1, 2, and 5-8, Karim et al. teach polypeptides which modulate PTH in order to modulate calcium levels (i.e. peptides which are “calcium-sensing receptor agonist” and “osteogenic growth peptide-like peptide or stimulator of bone marrow mesenchymal stem cells”) including CARRRAR (SEQ ID NOs: 2, 3, 12, 26, 146; present SEQ ID NOs: 1, 7-11, and 21-27) or CRRARAR (SEQ ID NO: 25; present SEQ ID NO: 20) and variable peptide sequences which encompass CRKKRAR (present SEQ ID NO: 19; K is a conservative amino acid substitution for R also) wherein all L amino acids are utilized, all D amino acids are utilized, or a mixture of L and D amino acids are utilized; the N- and/or C-terminus is modified wherein the modification is acetylation, amidation, PEGylation, benzoyl, alkylation, sulfonylation, sulfonamide; a peptide with a cysteine/thiol-containing group are linked to another peptide with a cysteine/thiol-containing group to form disulfide bonds wherein the peptides with cysteine/thiol-containing groups are the same or different (i.e. both are “calcium-sensing receptor agonist” and/or “osteogenic growth peptide-like peptide or stimulator of bone marrow mesenchymal stem cells”); thiol-containing group may also be homocysteine (please refer to the entire specification particularly the abstract; paragraphs 3-22, 25-33, 41, 43-49, 51-53, 60, 62-64, 71, 73, 74, 81, 89-91, 93-99, 102, 103, 107-109, 111, 116, 127-144, 153; Tables).
For present claims 1, 2, and 5-8, Newcomb et al. teach peptides that alter class E voltage-gated calcium channels including SEQ ID NO: 19 (CRYMFGGC; present SEQ ID NO: 5 YAibFGGC; P and G are conservative amino acid substitutions for M – present SEQ ID NOs: 13 and 16-18) with disulfide bridging patterns and N-terminal acetylation (please refer to the entire specification particularly the abstract; columns 1-5, 12, 13, 18, 24).
For present claims 1, 2, and 5-8, Tran et al. teach the benefits of adding Aib into peptides (i.e. substituting at least one amino acid for Aib) including increased peptide stability and decreased enzymatic degradation (please refer to the entire reference particularly the abstract; Introduction).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements (e.g. various calcium modulating peptides, addition of Aib for stability) as claimed by known methods (i.e. making dimers via disulfide linkage of cysteine residues) with no change in the respective function (e.g. function of the peptides is unchanged) and the combination would have yielded predictable results (e.g. multiple calcium modulating peptides with increased stability) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of a peptide which modulates calcium; methionine) for another (i.e. species of a peptide - CRYMFGGC - which modulates calcium; conservative amino acid substitution of proline or glycine; Aib) would have yielded predictable results (i.e. modulation of calcium; increased stability) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because a particular known technique (i.e. making peptide dimers via linking cysteine residues; substituting at least one amino acid with Aib for increased stability) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
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/AMBER D STEELE/Primary Examiner, Art Unit 1658