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 1-15 were originally filed May 16, 2022.
The preliminary amendment received May 16, 2022 amended claims 3-5, 8-11, 14, and 15 and cancelled claim 13.
Please note: claim 5 does not have a status identifier.
The amendment received September 16, 2025 amended claims 1, 4, 10, 12, and 15; cancelled claim 14; and added new claims 16-18.
Please note: claim 5 does not have a status identifier.
The amendment received February 24, 2026 amended claims 1, 5, 10, and 17 and cancelled claims 2 and 4.
Please note: the text of cancelled claims should not be present (see claims 2 and 4). See MPEP § 714 and 37 CFR 1.121.
Claims 1, 3, 5-12 and 15-18 are currently pending.
Claims 1, 5, 6, 10, and 17 are currently under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-12, 17, and 18) in the reply filed on September 16, 2025 is acknowledged.
Please note: present new claim 16 is Group IV drawn to a method of detection. The same reference utilized to break Unity of Invention for Groups I-III applies to new Group IV.
Claims 15 and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected methods, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 16, 2025.
Applicant’s election without traverse of SEQ ID NO: 1, a ligand of integrins avb6 and avb8, a macrocyclic structure with all residues that comprise a triazole-bridged macrocyclic scaffold that stabilizes the a-helix of the peptide, and a radioisotope or cytotoxic drug or an antibody fragment as the “species” in the reply filed on September 16, 2025 is acknowledged.
Claims 3, 7-9, 11, 12, and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.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 September 16, 2025.
Please note: a macrocyclic structure with all residues that comprise a triazole-bridged macrocyclic scaffold that stabilizes the a-helix of the peptide is not a single, specific species. The election is a subgenus, therefore, the subgenus was searched.
Please note: a radioisotope or cytotoxic drug or an antibody fragment is not a single, specific species.
Please note: the comments of record regarding the Greek letters in present claim 9 is noted. However, it is respectfully noted that the numbering in present claims 7 and 9 does not correspond with the 25mer of present SEQ ID NO: 1. It is noted that the numbering appears to correspond with wildtype chromogranin A. However, this should be clarified in the claims. The numbering also calls to question what is required by the claim (e.g. fragment or full length chromogranin A). Furthermore, regarding X1 and X2 of present claim 9, all variables residues must be defined in the claim. It is improper to import claim limitations from the specification. See MPEP § 2111.01 II. Furthermore, it is unclear if the limitations in parentheses in claim 7 are part of the claim or not.
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/EP2020/082257 which claims foreign priority to EP 19209484.5 filed November 15, 2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on February 5, 2026 is being considered by the examiner.
Specification
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.
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.
Withdrawn Objections
The objection to the disclosure regarding an embedded hyperlink and/or other form of browser-executable code is withdrawn in view of the amendment received February 24, 2026 and March 31, 2026.
The objection to the disclosure regarding two boxes with question marks is withdrawn in view of the amendment received February 24, 2026 and March 31, 2026.
The objection to claim 1 regarding the spacing of line 2 should be corrected is withdrawn in view of the amendment received February 24, 2026.
The objection to claims 2, 4-6, 10, and 17 regarding the preamble of the dependent claim should match the independent claim is withdrawn in view of the amendment received February 24, 2026.
The objection to claim 10 regarding “being fused” should simply be “fused” to show a structure for the product instead of a potential method step is withdrawn in view of the amendment received February 24, 2026.
The objection to claim 17 regarding the spacing of lines 4 and 6 should be corrected is withdrawn in view of the amendment received February 24, 2026.
Maintained Objection
Claim Objections
Claim 17 is objected to because of the following informalities: the Markush group should have a single conjunction. Appropriate correction is required. Please also see claim 18.
Arguments and Response
Applicants’ arguments directed to the objection for claim 17 were considered but are not persuasive for the following reasons.
Applicants contend that claim 17 was amended to contain a single conjunction.
Applicants’ arguments are not convincing since claim 17 still contains multiple conjunctions (see lines 2, 5).
Withdrawn Rejections
The rejection of claim 5 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 is withdrawn in view of the amendment received February 24, 2026.
The rejection of claim 2 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of the amendment received February 24, 2026 which cancelled the claim.
New Rejections Necessitated by Amendment
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.
Claim 6 is 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 new matter rejection. Support in the originally filed specification for a head-to-tail cyclic form comprising a triazole-bridge is not present. Triazole bridges are only referred to in the form of a staple and not a head-to tail orientation. See pages 3, 5-7, 14, 21, and 27 of the originally filed specification.
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, 5, 6, 10, and 17 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 presently claimed peptide or functional fragment thereof. For example, it is unclear what the scope of “comprises FETLRGDLRILSIL (SEQ ID NO: 2)” is (see the above Sequence Interpretation section; e.g. is the full-length sequence require or not, is 100% identity required or not, etc.).
Claims 1, 5, 6, 10, and 17 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.
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 1 recites the broad recitation SEQ ID NO: 2 (14mer; peptide or peptide fragment), and the claim also recites SEQ ID NO: 1 (25mer; peptide) 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. Please note: if “the peptide” was deleted from line 5, the rejection would be withdrawn.
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. One of skill in the art would not be able to determine the scope of the presently claimed peptide or functional fragment thereof. For example, the originally filed specification does not refer to a head-to-tail cyclic form in which a triazole bridge is utilized. Therefore, it is unclear if the triazole bridge can be present or not.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 6 depends on claim 5. Claim 5 requires a head-to-tail cyclic form while claim 6 requires a triazole bridge. A triazole bridge between the N- and C-terminus is not taught in the present specification. Therefore, it appears that claim 6 fails to further limit claim 5. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Maintained and/or Modified* Rejections
*wherein the modification is due to amendment
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 10, and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to chromogranin A without significantly more. The claims recite a peptide with at least 80% identity with SEQ ID NO: 1 (i.e. fragment of chromogranin A) or a functional fragment thereof of SEQ ID NO: 2 (i.e. FETLRGDLRILSIL). This judicial exception is not integrated into a practical application because the present claims are drawn to the peptide only. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because an “agent” and/or a “therapeutic agent” may be interpreted as simply the remainder of the full-length chromogranin A.
RESULT 1
G1QDB7_MYOLU
ID G1QDB7_MYOLU Unreviewed; 115 AA.
AC G1QDB7;
DT 19-OCT-2011, integrated into UniProtKB/TrEMBL.
DT 19-OCT-2011, sequence version 1.
DT 05-FEB-2025, entry version 48.
DE RecName: Full=Chromogranin-A {ECO:0000256|ARBA:ARBA00040787};
GN Name=LOC102439979 {ECO:0000313|Ensembl:ENSMLUP00000021700.1};
OS Myotis lucifugus (Little brown bat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Chiroptera; Yangochiroptera; Vespertilionidae;
OC Myotis.
OX NCBI_TaxID=59463 {ECO:0000313|Ensembl:ENSMLUP00000021700.1, ECO:0000313|Proteomes:UP000001074};
RN [1] {ECO:0000313|Ensembl:ENSMLUP00000021700.1, ECO:0000313|Proteomes:UP000001074}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0000313|Ensembl:ENSMLUP00000021700.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (OCT-2024) to UniProtKB.
CC -!- FUNCTION: Strongly inhibits glucose induced insulin release from the
CC pancreas. {ECO:0000256|ARBA:ARBA00037544}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, neuronal
CC dense core vesicle {ECO:0000256|ARBA:ARBA00037849}. Secreted
CC {ECO:0000256|ARBA:ARBA00004613}.
CC -!- SIMILARITY: Belongs to the chromogranin/secretogranin protein family.
CC {ECO:0000256|ARBA:ARBA00005723}.
CC ---------------------------------------------------------------------------
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DR EMBL; AAPE02071497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; G1QDB7; -.
DR STRING; 59463.ENSMLUP00000021700; -.
DR Ensembl; ENSMLUT00000025207.1; ENSMLUP00000021700.1; ENSMLUG00000022877.1.
DR eggNOG; ENOG502RZBD; Eukaryota.
DR GeneTree; ENSGT00940000154206; -.
DR HOGENOM; CLU_2114512_0_0_1; -.
DR InParanoid; G1QDB7; -.
DR Proteomes; UP000001074; Unassembled WGS sequence.
DR GO; GO:0042583; C:chromaffin granule; IEA:TreeGrafter.
DR GO; GO:0005615; C:extracellular space; IEA:TreeGrafter.
DR GO; GO:0098992; C:neuronal dense core vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0086030; P:adenylate cyclase-activating adrenergic receptor signaling pathway involved in cardiac muscle relaxation; IEA:TreeGrafter.
DR GO; GO:0042742; P:defense response to bacterium; IEA:TreeGrafter.
DR GO; GO:0033604; P:negative regulation of catecholamine secretion; IEA:TreeGrafter.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:TreeGrafter.
DR InterPro; IPR001819; Chromogranin_AB.
DR InterPro; IPR018054; Chromogranin_CS.
DR InterPro; IPR001990; Granin.
DR PANTHER; PTHR10583; CHROMOGRANIN; 1.
DR PANTHER; PTHR10583:SF1; CHROMOGRANIN-A; 1.
DR Pfam; PF01271; Granin; 1.
DR PRINTS; PR00659; CHROMOGRANIN.
DR PROSITE; PS00423; GRANINS_2; 1.
PE 3: Inferred from homology;
KW Cytoplasmic vesicle {ECO:0000256|ARBA:ARBA00023329};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157};
KW Reference proteome {ECO:0000313|Proteomes:UP000001074};
KW Secreted {ECO:0000256|ARBA:ARBA00022525}; Signal {ECO:0000256|SAM:SignalP}.
FT SIGNAL 1..18
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 19..115
FT /note="Chromogranin-A"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5003419499"
FT REGION 88..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 115 AA; 12809 MW; C5AD4ED0A8E6C3CC CRC64;
Query Match 89.4%; Score 59; Length 115;
Best Local Similarity 92.9%;
Matches 13; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 FETLRGDLRILSIL 14
||||||| ||||||
Db 57 FETLRGDERILSIL 70
RESULT 1
G1QDB7_MYOLU
ID G1QDB7_MYOLU Unreviewed; 115 AA.
AC G1QDB7;
DT 19-OCT-2011, integrated into UniProtKB/TrEMBL.
DT 19-OCT-2011, sequence version 1.
DT 05-FEB-2025, entry version 48.
DE RecName: Full=Chromogranin-A {ECO:0000256|ARBA:ARBA00040787};
GN Name=LOC102439979 {ECO:0000313|Ensembl:ENSMLUP00000021700.1};
OS Myotis lucifugus (Little brown bat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Chiroptera; Yangochiroptera; Vespertilionidae;
OC Myotis.
OX NCBI_TaxID=59463 {ECO:0000313|Ensembl:ENSMLUP00000021700.1, ECO:0000313|Proteomes:UP000001074};
RN [1] {ECO:0000313|Ensembl:ENSMLUP00000021700.1, ECO:0000313|Proteomes:UP000001074}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0000313|Ensembl:ENSMLUP00000021700.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (OCT-2024) to UniProtKB.
CC -!- FUNCTION: Strongly inhibits glucose induced insulin release from the
CC pancreas. {ECO:0000256|ARBA:ARBA00037544}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, neuronal
CC dense core vesicle {ECO:0000256|ARBA:ARBA00037849}. Secreted
CC {ECO:0000256|ARBA:ARBA00004613}.
CC -!- SIMILARITY: Belongs to the chromogranin/secretogranin protein family.
CC {ECO:0000256|ARBA:ARBA00005723}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AAPE02071497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; G1QDB7; -.
DR STRING; 59463.ENSMLUP00000021700; -.
DR Ensembl; ENSMLUT00000025207.1; ENSMLUP00000021700.1; ENSMLUG00000022877.1.
DR eggNOG; ENOG502RZBD; Eukaryota.
DR GeneTree; ENSGT00940000154206; -.
DR HOGENOM; CLU_2114512_0_0_1; -.
DR InParanoid; G1QDB7; -.
DR Proteomes; UP000001074; Unassembled WGS sequence.
DR GO; GO:0042583; C:chromaffin granule; IEA:TreeGrafter.
DR GO; GO:0005615; C:extracellular space; IEA:TreeGrafter.
DR GO; GO:0098992; C:neuronal dense core vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0086030; P:adenylate cyclase-activating adrenergic receptor signaling pathway involved in cardiac muscle relaxation; IEA:TreeGrafter.
DR GO; GO:0042742; P:defense response to bacterium; IEA:TreeGrafter.
DR GO; GO:0033604; P:negative regulation of catecholamine secretion; IEA:TreeGrafter.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:TreeGrafter.
DR InterPro; IPR001819; Chromogranin_AB.
DR InterPro; IPR018054; Chromogranin_CS.
DR InterPro; IPR001990; Granin.
DR PANTHER; PTHR10583; CHROMOGRANIN; 1.
DR PANTHER; PTHR10583:SF1; CHROMOGRANIN-A; 1.
DR Pfam; PF01271; Granin; 1.
DR PRINTS; PR00659; CHROMOGRANIN.
DR PROSITE; PS00423; GRANINS_2; 1.
PE 3: Inferred from homology;
KW Cytoplasmic vesicle {ECO:0000256|ARBA:ARBA00023329};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157};
KW Reference proteome {ECO:0000313|Proteomes:UP000001074};
KW Secreted {ECO:0000256|ARBA:ARBA00022525}; Signal {ECO:0000256|SAM:SignalP}.
FT SIGNAL 1..18
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 19..115
FT /note="Chromogranin-A"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5003419499"
FT REGION 88..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 115 AA; 12809 MW; C5AD4ED0A8E6C3CC CRC64;
Query Match 94.3%; Score 116; Length 115;
Best Local Similarity 96.0%;
Matches 24; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 FETLRGDLRILSILRHQNLLKELQD 25
||||||| |||||||||||||||||
Db 57 FETLRGDERILSILRHQNLLKELQD 81
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 101 as being drawn to a judicial exception for claims 1, 10, and 17 were considered but are not persuasive for the following reasons.
Applicants contend that both the peptide and the functional fragment thereof must contain a leucine at residue 8 of either SEQ ID NO: 1 or 2 which provides a different function from chromogranin A (i.e. ligand for both avb6 and avb8).
Applicants’ arguments are not convincing since a leucine at position 8 of either SEQ ID NO: 1 or 2 is not required by the present claims (see 80% identical to SEQ ID NO: 1 and open comprises language for SEQ ID NO: 2). Applicants should clarify the structure of the presently claimed peptides.
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, 10, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Steward et al. U.S. Patent Application Publication 2008/0032930 published February 7, 2008.
For present claims 1, 2, 4, 10, and 17, Steward et al. teach chromogranin A of SEQ ID NO: 94 (94.3% identity with present SEQ ID NO: 1) fused to linkers or spacers (i.e. agent) and further fused to a therapeutic agent (please refer to the entire specification particularly the abstract; paragraphs 88-93, 235-239, 269, 270).
Therefore, the teachings of Steward et al. anticipate the presently claimed peptide.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102 (a)(1) as being anticipated by Steward et al. for claims 1, 10, and 17 were considered but are not persuasive for the following reasons.
Applicants contend that both the peptide and the functional fragment thereof must contain a leucine at residue 8 of either SEQ ID NO: 1 or 2.
Applicants’ arguments are not convincing since the teachings of Steward et al. anticipate the peptides of the instant claims. A leucine at position 8 of either SEQ ID NO: 1 or 2 is not required by the present claims (see 80% identical to SEQ ID NO: 1 and open comprises language for SEQ ID NO: 2). Applicants should clarify the structure of the presently claimed peptides.
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, 5, 6, 10, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Steward et al. U.S. Patent Application Publication 2008/0032930 published February 7, 2008 and Lau et al., 2015, A two-component ‘double-click’ approach to peptide stapling, Nature Protocols, 10(4): 585-594.
For present claims 1, 5, 6, 10, and 17, Steward et al. teach chromogranin A of SEQ ID NO: 94 (94.3% identity with present SEQ ID NO: 1) fused to linkers or spacers (i.e. agent) and further fused to a therapeutic agent (please refer to the entire specification particularly the abstract; paragraphs 88-93, 235-239, 269, 270).
For present claims 1, 5, 6, 10, and 17, Lau et al. teach utilizing methods of double click stapling to form macrocyclic peptides comprising a triazole bridge to enhance the binding affinity, proteolytic stability, and cellular activity of peptides wherein the staple is formed head-to-tail (e.g. N-terminus to C-terminus) (please refer to the entire reference particularly the abstract; Introduction, Development and applications of the protocol; Figure 1).
The claims would have been obvious because a particular known technique (i.e. double click stapling to form macrocyclic peptides comprising a triazole bridge) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Steward et al. and Lau et al. for claims 1, 5, 6, 10, and 17 were considered but are not persuasive for the following reasons.
Applicants contend that both the peptide and the functional fragment thereof must contain a leucine at residue 8 of either SEQ ID NO: 1 or 2.
Applicants’ arguments are not convincing since the teachings of Steward et al. and Lau et al. render the peptide of the instant claims prima facie obvious. A leucine at position 8 of either SEQ ID NO: 1 or 2 is not required by the present claims (see 80% identical to SEQ ID NO: 1 and open comprises language for SEQ ID NO: 2). Applicants should clarify the structure of the presently claimed peptides. Regarding Table 3a, SEQ ID NO: 16 still has activity for both avb6 and avb8 simply at a higher dose than SEQ ID NO: 1. Regarding stapling, applicants have deleted stapling from the present claims.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 10, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/844,832 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both the present claims and the claims of copending Application No. 18/844,832 (reference application) are drawn to SEQ ID NO: 3 (i.e. present SEQ ID NO: 1) with linkers/spacers (i.e. agent) and therapeutic agents.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over copending Application No. 18/844,832 (reference application) for claims 1, 10, and 17 were considered but are not persuasive for the following reasons.
Applicants request that the provisional rejection be deferred until allowable subject matter is indicated.
Applicants’ arguments are not convincing since the claimed invention of copending Application No. 18/844,832 (reference application) renders obvious the peptides of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Claims 1, 5, 6, 10, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/844,832 in view of Lau et al., 2015, A two-component ‘double-click’ approach to peptide stapling, Nature Protocols, 10(4): 585-594.
Both the present claims and the claims of copending Application No. 18/844,832 (reference application) are drawn to SEQ ID NO: 3 (i.e. present SEQ ID NO: 1) with linkers/spacers (i.e. agent) and therapeutic agents.
Lau et al. teach utilizing methods of double click stapling to form macrocyclic peptides comprising a triazole bridge to enhance the binding affinity, proteolytic stability, and cellular activity of peptides wherein stapling is head-to-tail (please refer to the entire reference particularly the abstract; Introduction, Development and applications of the protocol; Figure 1).
The claims would have been obvious because a particular known technique (i.e. double click stapling to form macrocyclic peptides comprising a triazole bridge) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
This is a provisional nonstatutory double patenting rejection.
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over copending Application No. 18/844,832 in view of Lau et al. for claims 1, 5, 6, 10, and 17 were considered but are not persuasive for the following reasons.
Applicants request that the provisional rejection be deferred until allowable subject matter is indicated.
Applicants’ arguments are not convincing since the claimed invention of copending Application No. 18/844,832 in view of Lau et al. renders obvious the peptide of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Claims 1, 10, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 19/113,135 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both the present claims and the claims of copending Application No. 19/113,135 (reference application) are drawn to SEQ ID NOs: 8-10 (present SEQ ID NO: 1) fused to antitumoral agents.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over copending Application No. 19/113,135 (reference application) for claims 1, 10, and 17 were considered but are not persuasive for the following reasons.
Applicants request that the provisional rejection be deferred until allowable subject matter is indicated.
Applicants’ arguments are not convincing since the claimed invention of copending Application No. 19/113,135 (reference application) renders obvious the peptide of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Claims 1, 5, 6, 10, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 19/113,135 in view of Lau et al., 2015, A two-component ‘double-click’ approach to peptide stapling, Nature Protocols, 10(4): 585-594.
Both the present claims and the claims of copending Application No. 19/113,135 (reference application) are drawn to SEQ ID NOs: 8-10 (present SEQ ID NO: 1) fused to antitumoral agents.
Lau et al. teach utilizing methods of double click stapling to form macrocyclic peptides comprising a triazole bridge to enhance the binding affinity, proteolytic stability, and cellular activity of peptides in a head-to-tail formation (please refer to the entire reference particularly the abstract; Introduction, Development and applications of the protocol; Figure 1).
The claims would have been obvious because a particular known technique (i.e. double click stapling to form macrocyclic peptides comprising a triazole bridge) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
This is a provisional nonstatutory double patenting rejection.
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over copending Application No. 19/113,135 in view of Lau et al. for claims 1, 5, 6, 10, and 17 were considered but are not persuasive for the following reasons.
Applicants request that the provisional rejection be deferred until allowable subject matter is indicated.
Applicants’ arguments are not convincing since the claimed invention of copending Application No. 19/113,135 in view of Lau et al. renders obvious the peptide of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
U.S. Patent Application Publication 2015/0376579
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Future Communications
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER D STEELE whose telephone number is (571)272-5538. The examiner can normally be reached M-F 8-5.
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/AMBER D STEELE/Primary Examiner, Art Unit 1658
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