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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 20, 2026 has been entered.
Status of the Claims
Claims 1-85 were originally filed March 15, 2022.
The preliminary amendment received March 15, 2022 canceled claims 2 and 23-85 and amended claims 3-6, 13, 15, 17, 18, and 20-22.
The amendment received March 20, 2025 changed the status identifiers only.
The amendment received October 10, 2025 amended claims 1, 3, 5, 13-16, and 18.
The amendment received March 20, 2026 amended claims 1 and 7.
Claims 1 and 3-22 are currently pending.
Claims 1, 3, 5, 7, and 9-12 are currently under consideration.
Election/Restrictions
Applicants elected, without traverse, DPR, an N-terminal amino acid side chain that is cyclized to a C-terminal amino acid side chain with a lactam bridge, and SEQ ID NO: 12 (N-terminal Glu and C-terminal Lys) as the species in the reply filed on March 20, 2025. Claims 4, 6, 8, and 13-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Please note: applicants neglected to elect the functions for species A-C, therefore, the functional claims (except claims 3 and 5) are withdrawn.
Please note: SEQ ID NO: 12 has DPR at residues 6-8.
Please note: applicants neglected to designate each region of SEQ ID NO: 12.
Priority
The present application is a 371 (National Stage) of PCT/US2021/035799 filed June 3, 2021 which claims the benefit of 63/034,395 filed June 3, 2020.
Withdrawn Objections
The objection to the drawings regarding Figures 5B, 5C, 5F, 5I, and 11A as being illegible is withdrawn. It is respectfully noted that if the application is ever allowed, publications may object to the drawings as being illegible.
The objection to claim 7 regarding “comprises a one or more” should read “comprises one or more” is withdrawn in view of the amendment received March 20, 2026.
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 deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
See Figures 1B, 1C, and 2. Figures 1B and 1C are chemical structures for peptides. The peptides have more than four specifically defined amino acid residues and, therefore, require a SEQ ID NO: and inclusion in the CRF and the sequence listing. Figure 2 has at least four cysteine residues and requires a SEQ ID NO: and inclusion in the CRF and the sequence listing.
Applicants contend that the figures are only meant as illustrative examples. Applicants arguments are not persuasive because Figures 1B, 1C, and 2 contain amino acid sequences as discussed above.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
B. Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825. This application contains a “Sequence Listing” as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3)). A copy of the "Sequence Listing" in computer readable form (CRF) has been submitted; however, the content of the CRF does not comply with one or more of the requirements of 37 CFR 1.822 through 1.824, as indicated in the "Error Report" that indicates the "Sequence Listing" could not be accepted. Refer to attachment or document "Computer Readable Form (CRF) for Sequence Listing – Defective" dated 4/16/2026 (i.e. ST.25 format required but ST.26 format was filed).
Required response – Applicant must provide:
A replacement "Sequence Listing" part of the disclosure, as described above in item 1); together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 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 replacement "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 and
An amendment to the specification to remove the “Sequence Listing previously submitted as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3))
If the replacement "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, Applicant must also provide:
A CRF in accordance with 1.821(e)(1) or 1.821(e)(2) as required by 37 CFR 1.825(b)(6)(ii); and
Statement according to item 2) a) or b) above.
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.
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.
Withdrawn Rejections
The rejection of claims 1, 3, 5, 7, and 9-12 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 March 20, 2026.
The rejection of claims 1, 3, 5, 7, 9, and 11 under 35 U.S.C. 102(a)(1) as being anticipated by McIntosh WO 2014/194284 published December 4, 2014 is withdrawn in view of the amendment received March 20, 2026.
Maintained and/or Modified Rejections
Claim Rejections - 35 USC § 112
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 3 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 3 depends on independent claim 1. Independent claim 1 requires the structure of SEQ ID NOs: 7-12, 17-19, 24, or 25. Claim 3 simply refers to the function of the sequences. Therefore, claim 3 fails to further limit the scope of independent claim 1. 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.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(d) as being of improper dependent form for claim 3 were considered but are not persuasive for the following reasons.
Applicants contend that since claim 3 refers to a 5% binding affinity, that the claim further limits independent claim 1.
Applicants’ arguments are not convincing since a more accurate argument would be providing the binding affinity for each of SEQ ID NOs: 7-12, 17-19, 24, and 25 and then limiting claim 3 to any SEQ ID NO: which has 5 % binding affinity.
Claim 5 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 5 depends on independent claim 1. Independent claim 1 requires the structure of SEQ ID NOs: 7-12, 17-19, 24, or 25. Claim 5 simply refers to the function of the sequences. Therefore, claim 3 fails to further limit the scope of independent claim 1. 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.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(d) as being of improper dependent form for claim 5 were considered but are not persuasive for the following reasons.
Applicants contend that since claim 5 refers to a specific IC50 value, that the claim further limits independent claim 1.
Applicants’ arguments are not convincing since a more accurate argument would be providing the IC50 value for each of SEQ ID NOs: 7-12, 17-19, 24, and 25 and then limiting claim 5 to any SEQ ID NO: which has the recited IC50 value.
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, 3, and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Iadonato et al. WO 2016/073949 published May 12, 2016.
For present claims 1, 3, and 5, Iadonato et al. teach a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NO: 28 (100% identity except for the missing N-terminal Glu and C-terminal Lys of present SEQ ID NO: 12) wherein X can be Tyr, mono-iodo-tyrosine, or 3-iodo-tyrosine, and lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5). Iadonato et al. also teach SEQ ID NO: 5 which has the same length and 100% identity to present SEQ ID NOs: 17-19 (i.e. GCCTDPRCCit3-iodo-YQCY; see Table 1 wherein X11 is citrulline and X12 is 3-iodo-tyrosine).
RESULT 4
BCQ37026
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
ID BCQ37026 standard; peptide; 13 AA.
XX
AC BCQ37026;
XX
DT 30-JUN-2016 (first entry)
XX
DE Conus regius alpha-conotoxin RgIA analog peptide, SEQ ID:28.
XX
KW Alpha-conotoxin RgIA; analgesic; antiinflammatory; cancer;
KW chronic inflammation; endometriosis; fibromyalgia;
KW inflammatory bowel disease; inflammatory disease; metabolic disorder;
KW neuropathic pain; neuropathy; neuroprotective; pain; protein therapy;
KW sarcoidosis; sepsis; skin burns; therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Disulfide-bond 2..8
FT Disulfide-bond 3..12
FT Modified-site 10
FT /note= "3-iodo-Tyrosine"
FT Modified-site 13
FT /note= "C-terminal amide"
XX
CC PN WO2016073949-A1.
XX
CC PD 12-MAY-2016.
XX
CC PF 06-NOV-2015; 2015WO-US059613.
XX
PR 07-NOV-2014; 2014US-0123123P.
XX
CC PA (KINE-) KINETA THREE LLP.
XX
CC PI Iadonato SP, Munoz EJ;
XX
DR WPI; 2016-290272/35.
XX
CC PT New conotoxin peptide is alpha-9-alpha-10 subtype of nicotinic
CC PT acetylcholine receptor inhibitor, useful for treating a condition that is
CC PT pain, neuropathy, cancer, and inflammatory condition e.g. sepsis,
CC PT endometriosis and fibromyalgia.
XX
CC PS Example 1; SEQ ID NO 28; 58pp; English.
XX
CC The present invention relates to novel modified conotoxin analog peptides
CC or cone snail proteins (CSP) of alpha-conotoxin peptide RgIA derived from
CC predatory marine snails (e.g., Conus regius). The conotoxin analog
CC peptides block the alpha-9-alpha-10 subtype of the nicotinic
CC acetylcholine receptor (nAChR). The invention further discloses: (1) a
CC pharmaceutical composition comprising the conotoxin peptide and a
CC pharmaceutically acceptable salt; and (2) a method for treating at least
CC one condition associated with the alpha-9-alpha-10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject, which involves
CC administering to the subject a therapeutically effective amount of the
CC conotoxin peptide or the composition comprising the conotoxin peptide,
CC thereby treating the condition. The conotoxin peptide and pharmaceutical
CC composition of the invention are useful for treating at least one
CC condition associated with nAChR in a subject, where: the condition is
CC pain, an inflammatory condition or neuropathy; the pain includes general
CC pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain
CC and/or pain induced by peripheral nerve damage, inflammatory disorder, a
CC metabolic disorder, cancer, chemotherapy, surgical procedure or burn, or
CC cancer-related chronic pain and/or cancer-related neuropathy;
CC inflammatory condition comprises inflammation, chronic inflammation,
CC rheumatic disease, sepsis, fibromyalgia, inflammatory bowel disease,
CC sarcoidosis, endometriosis, uterine fibroids, an inflammatory skin
CC disease, an inflammatory condition of lungs, a disease associated with
CC inflammation of nervous system, periodontal disease or cardiovascular
CC disease; the inflammatory condition is mediated by immune cells, and the
CC inflammatory condition is long-term inflammation and peripheral
CC neuropathy following injury; and the condition is cancer. The present
CC sequence represents a Conus regius alpha-conotoxin RgIA analog peptide
CC which is used in preparing the pharmaceutical composition.
XX
SQ Sequence 13 AA;
Query Match 89.2%; Score 83; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCY 14
|||||||||||||
Db 1 GCCTDPRCRXQCY 13
Therefore, the teachings of Iadonato et al. anticipate the presently claimed a-RgIA4 peptide analog.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102 (a)(1) as being anticipated by Iadonato et al. for claims 1, 3, and 5 were considered but are not persuasive for the following reasons.
Applicants contend that a sequence with 100% identity to present SEQ ID NO: 12 is required by independent claim 1 and Iadonato et al. teach a peptide with less than 100% identity to present SEQ ID NO: 12 due to the missing N-terminal Glu and C-terminal Lys of present SEQ ID NO: 12.
Applicants’ arguments are not convincing since the teachings of Iadonato et al. anticipate the a-RgIA4 peptide analog of the instant claims.
Iadonato et al. also teach SEQ ID NO: 5 which has the same length and 100% identity to present SEQ ID NOs: 17-19 (i.e. GCCTDPRCCit3-iodo-YQCY; see Table 1 wherein X11 is citrulline and X12 is 3-iodo-tyrosine).
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, 3, 5, 7, and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Iadonato et al. WO 2016/073949 published May 12, 2016 and Schumann et al., 2002, Synthesis and biological activities of new side chain and backbone cyclic bradykinin analogues, J Peptide Res, 60: 128-140.
For present claims 1, 3, 5, 7, and 9-12, Iadonato et al. teach a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NO: 28 (100% identity except for the missing N-terminal Glu and C-terminal Lys of present SEQ ID NO: 12) wherein X can be Tyr, mono-iodo-tyrosine, or 3-iodo-tyrosine, and lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5). Iadonato et al. also teach SEQ ID NO: 5 which has the same length and 100% identity to present SEQ ID NOs: 17-19 (i.e. GCCTDPRCCit3-iodo-YQCY; see Table 1 wherein X11 is citrulline and X12 is 3-iodo-tyrosine).
RESULT 4
BCQ37026
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
ID BCQ37026 standard; peptide; 13 AA.
XX
AC BCQ37026;
XX
DT 30-JUN-2016 (first entry)
XX
DE Conus regius alpha-conotoxin RgIA analog peptide, SEQ ID:28.
XX
KW Alpha-conotoxin RgIA; analgesic; antiinflammatory; cancer;
KW chronic inflammation; endometriosis; fibromyalgia;
KW inflammatory bowel disease; inflammatory disease; metabolic disorder;
KW neuropathic pain; neuropathy; neuroprotective; pain; protein therapy;
KW sarcoidosis; sepsis; skin burns; therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Disulfide-bond 2..8
FT Disulfide-bond 3..12
FT Modified-site 10
FT /note= "3-iodo-Tyrosine"
FT Modified-site 13
FT /note= "C-terminal amide"
XX
CC PN WO2016073949-A1.
XX
CC PD 12-MAY-2016.
XX
CC PF 06-NOV-2015; 2015WO-US059613.
XX
PR 07-NOV-2014; 2014US-0123123P.
XX
CC PA (KINE-) KINETA THREE LLP.
XX
CC PI Iadonato SP, Munoz EJ;
XX
DR WPI; 2016-290272/35.
XX
CC PT New conotoxin peptide is alpha-9-alpha-10 subtype of nicotinic
CC PT acetylcholine receptor inhibitor, useful for treating a condition that is
CC PT pain, neuropathy, cancer, and inflammatory condition e.g. sepsis,
CC PT endometriosis and fibromyalgia.
XX
CC PS Example 1; SEQ ID NO 28; 58pp; English.
XX
CC The present invention relates to novel modified conotoxin analog peptides
CC or cone snail proteins (CSP) of alpha-conotoxin peptide RgIA derived from
CC predatory marine snails (e.g., Conus regius). The conotoxin analog
CC peptides block the alpha-9-alpha-10 subtype of the nicotinic
CC acetylcholine receptor (nAChR). The invention further discloses: (1) a
CC pharmaceutical composition comprising the conotoxin peptide and a
CC pharmaceutically acceptable salt; and (2) a method for treating at least
CC one condition associated with the alpha-9-alpha-10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject, which involves
CC administering to the subject a therapeutically effective amount of the
CC conotoxin peptide or the composition comprising the conotoxin peptide,
CC thereby treating the condition. The conotoxin peptide and pharmaceutical
CC composition of the invention are useful for treating at least one
CC condition associated with nAChR in a subject, where: the condition is
CC pain, an inflammatory condition or neuropathy; the pain includes general
CC pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain
CC and/or pain induced by peripheral nerve damage, inflammatory disorder, a
CC metabolic disorder, cancer, chemotherapy, surgical procedure or burn, or
CC cancer-related chronic pain and/or cancer-related neuropathy;
CC inflammatory condition comprises inflammation, chronic inflammation,
CC rheumatic disease, sepsis, fibromyalgia, inflammatory bowel disease,
CC sarcoidosis, endometriosis, uterine fibroids, an inflammatory skin
CC disease, an inflammatory condition of lungs, a disease associated with
CC inflammation of nervous system, periodontal disease or cardiovascular
CC disease; the inflammatory condition is mediated by immune cells, and the
CC inflammatory condition is long-term inflammation and peripheral
CC neuropathy following injury; and the condition is cancer. The present
CC sequence represents a Conus regius alpha-conotoxin RgIA analog peptide
CC which is used in preparing the pharmaceutical composition.
XX
SQ Sequence 13 AA;
Query Match 89.2%; Score 83; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCY 14
|||||||||||||
Db 1 GCCTDPRCRXQCY 13
For present claims 1, 3, 5, 7, and 9-12, Schumann et al. teach that Glu can be added to the N-terminus and Lys can be added to the C-terminus to make lactam bridges (please refer to the entire reference particularly the abstract; Tables 1-3).
All the claimed elements (i.e. N-terminal Glu and C-terminal Lys to form a lactam bridge instead of cyclization via a linker) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results 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. linker for N- to C-terminal cyclization) for another (i.e. N-terminal Glu and C-terminal Lys for lactam bridge formation) would have yielded predictable results (i.e. cyclization of the peptide) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. N-terminal Glu and C-terminal Lys for lactam bridge formation) 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).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Iadonato et al. and Schumann et al. for claims 1, 3, 5, 7, and 9-12 were considered but are not persuasive for the following reasons.
Applicants contend that that the results would be unpredictable and that hindsight reasoning was utilized.
Applicants’ arguments are not convincing since the teachings of Iadonato et al. and Schumann et al. render the a-RgIA4 peptide analog of the instant claims prima facie obvious.
Applicants’ representative should provide proof when alleging unpredictability (e.g. NPL, etc.).
Iadonato et al. teach a-RgIA/conotoxin peptide analog with lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide to increase therapeutic potential (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5).
Schumann et al. teach that Glu can be added to the N-terminus and Lys can be added to the C-terminus to make lactam bridges (please refer to the entire reference particularly the abstract; Tables 1-3).
The experimentation is not undo particularly considering that a-RgIA4 peptides already form disulfide bridges. However, RgIA is known in the art to being susceptible to poor oral bioavailability, short biological half-life, and low stability wherein cyclization can help improve these characteristics (see the art of record and, at least, Halai et al., 2011, Effects of Cyclization on Stability, Structure, and Activity of a-Conotoxin RgIA at the a9a10 Nicotinic Acetylcholine Receptor and GABAb Receptor, Journal of Medicinal Chemistry, 54: 6984-6992; additional references will be provided upon request). Therefore, one of skill in the art would look to cyclization methods to increase oral bioavailability, biological half-life, and stability of a-RgIA4 peptides and a-RgIA4 peptide analogs. The utilization of lactam bridges for cyclization is well-understood, routine, and conventional in the prior art. Additional reference will be provided upon request.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Claims 1, 3, 5, 7, and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over McIntosh WO 2014/194284 published December 4, 2014; Iadonato et al. WO 2016/073949 published May 12, 2016; and Schumann et al., 2002, Synthesis and biological activities of new side chain and backbone cyclic bradykinin analogues, J Peptide Res, 60: 128-140.
For present claims 1, 3, 5, 7, and 9-12, McIntosh teaches a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NOs: 13 and 18 (100% identity except for the missing N-terminal Glu, Tyr instead of 3-iodo-tyrosine, and a C-terminal Arg instead of Lys of present SEQ ID NO: 12), utilizing mono-iodo-Tyr instead of Tyr to increase potency, conservative amino acid substitutions including Lys for Arg (i.e. C-terminal Lys), and adding an N-terminal pyroglutamate (i.e. conservative amino acid substitution for Glu) wherein the N-terminal pyroglutamate and the C-terminal Lys may form a lactam bridge to “protect” the disulfide cysteine bridges (please refer to the entire specification particularly the abstract; paragraphs 3-7, 13, 15-25, 28, 30-35, 45, 59, 100, 102; Table 1; claims). Please note: McIntosh also teaches sequences broader in scope than SEQ DI NOs: 13 and 18 (e.g. SEQ ID NO: 22, paragraph 17).
RESULT 2
BBR01953
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BBR01953 standard; peptide; 14 AA.
XX
AC BBR01953;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 18, SEQ ID 18.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 18; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 14 AA;
Query Match 91.4%; Score 85; Length 14;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
RESULT 3
BBR01948
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BBR01948 standard; peptide; 15 AA.
XX
AC BBR01948;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 13, SEQ ID 13.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 13; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 15 AA;
Query Match 91.4%; Score 85; Length 15;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
For present claims 1, 3, 5, 7, and 9-12, Iadonato et al. teach a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NO: 28 (100% identity except for the missing N-terminal Glu and C-terminal Lys of present SEQ ID NO: 12) wherein X can be Tyr, mono-iodo-tyrosine, or 3-iodo-tyrosine, and lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5). Iadonato et al. also teach SEQ ID NO: 5 which has the same length and 100% identity to present SEQ ID NOs: 17-19 (i.e. GCCTDPRCCit3-iodo-YQCY; see Table 1 wherein X11 is citrulline and X12 is 3-iodo-tyrosine).
RESULT 4
BCQ37026
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
ID BCQ37026 standard; peptide; 13 AA.
XX
AC BCQ37026;
XX
DT 30-JUN-2016 (first entry)
XX
DE Conus regius alpha-conotoxin RgIA analog peptide, SEQ ID:28.
XX
KW Alpha-conotoxin RgIA; analgesic; antiinflammatory; cancer;
KW chronic inflammation; endometriosis; fibromyalgia;
KW inflammatory bowel disease; inflammatory disease; metabolic disorder;
KW neuropathic pain; neuropathy; neuroprotective; pain; protein therapy;
KW sarcoidosis; sepsis; skin burns; therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Disulfide-bond 2..8
FT Disulfide-bond 3..12
FT Modified-site 10
FT /note= "3-iodo-Tyrosine"
FT Modified-site 13
FT /note= "C-terminal amide"
XX
CC PN WO2016073949-A1.
XX
CC PD 12-MAY-2016.
XX
CC PF 06-NOV-2015; 2015WO-US059613.
XX
PR 07-NOV-2014; 2014US-0123123P.
XX
CC PA (KINE-) KINETA THREE LLP.
XX
CC PI Iadonato SP, Munoz EJ;
XX
DR WPI; 2016-290272/35.
XX
CC PT New conotoxin peptide is alpha-9-alpha-10 subtype of nicotinic
CC PT acetylcholine receptor inhibitor, useful for treating a condition that is
CC PT pain, neuropathy, cancer, and inflammatory condition e.g. sepsis,
CC PT endometriosis and fibromyalgia.
XX
CC PS Example 1; SEQ ID NO 28; 58pp; English.
XX
CC The present invention relates to novel modified conotoxin analog peptides
CC or cone snail proteins (CSP) of alpha-conotoxin peptide RgIA derived from
CC predatory marine snails (e.g., Conus regius). The conotoxin analog
CC peptides block the alpha-9-alpha-10 subtype of the nicotinic
CC acetylcholine receptor (nAChR). The invention further discloses: (1) a
CC pharmaceutical composition comprising the conotoxin peptide and a
CC pharmaceutically acceptable salt; and (2) a method for treating at least
CC one condition associated with the alpha-9-alpha-10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject, which involves
CC administering to the subject a therapeutically effective amount of the
CC conotoxin peptide or the composition comprising the conotoxin peptide,
CC thereby treating the condition. The conotoxin peptide and pharmaceutical
CC composition of the invention are useful for treating at least one
CC condition associated with nAChR in a subject, where: the condition is
CC pain, an inflammatory condition or neuropathy; the pain includes general
CC pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain
CC and/or pain induced by peripheral nerve damage, inflammatory disorder, a
CC metabolic disorder, cancer, chemotherapy, surgical procedure or burn, or
CC cancer-related chronic pain and/or cancer-related neuropathy;
CC inflammatory condition comprises inflammation, chronic inflammation,
CC rheumatic disease, sepsis, fibromyalgia, inflammatory bowel disease,
CC sarcoidosis, endometriosis, uterine fibroids, an inflammatory skin
CC disease, an inflammatory condition of lungs, a disease associated with
CC inflammation of nervous system, periodontal disease or cardiovascular
CC disease; the inflammatory condition is mediated by immune cells, and the
CC inflammatory condition is long-term inflammation and peripheral
CC neuropathy following injury; and the condition is cancer. The present
CC sequence represents a Conus regius alpha-conotoxin RgIA analog peptide
CC which is used in preparing the pharmaceutical composition.
XX
SQ Sequence 13 AA;
Query Match 89.2%; Score 83; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCY 14
|||||||||||||
Db 1 GCCTDPRCRXQCY 13
For present claims 1, 3, 5, 7, and 9-12, Schumann et al. teach that Glu can be added to the N-terminus and Lys can be added to the C-terminus to make lactam bridges (please refer to the entire reference particularly the abstract; Tables 1-3).
All the claimed elements (i.e. N-terminal Glu and C-terminal Lys to form a lactam bridge) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results 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. N-terminal pyroglutamate) for another (i.e. N-terminal Glu) would have yielded predictable results (i.e. cyclization of the peptide) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. N-terminal Glu and C-terminal Lys for lactam bridge formation) 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).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over McIntosh, Iadonato et al., and Schumann et al. for claims 1, 3, 5, 7, and 9-12 were considered but are not persuasive for the following reasons.
Applicants contend that that the results would be unpredictable and that hindsight reasoning was utilized.
Applicants’ arguments are not convincing since the teachings of McIntosh, Iadonato et al., and Schumann et al. render the a-RgIA4 peptide analog of the instant claims prima facie obvious.
Applicants’ representative should provide proof when alleging unpredictability (e.g. NPL, etc.).
McIntosh teaches a-RgIA/conotoxin peptide analogs wherein the N-terminal pyroglutamate and the C-terminal Lys may form a lactam bridge to “protect” the disulfide cysteine bridges (please refer to the entire specification particularly the abstract; paragraphs 3-7, 13, 15-25, 28, 30-35, 45, 59, 100, 102; Table 1; claims). McIntosh teaches various cyclization methods (please refer to the entire specification particularly paragraphs 30, 31).
Iadonato et al. teach a-RgIA/conotoxin peptide analog with lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide to increase therapeutic potential (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5).
Schumann et al. teach that Glu can be added to the N-terminus and Lys can be added to the C-terminus to make lactam bridges (please refer to the entire reference particularly the abstract; Tables 1-3).
The experimentation is not undo particularly considering that a-RgIA4 peptides already form disulfide bridges. However, RgIA is known in the art to being susceptible to poor oral bioavailability, short biological half-life, and low stability wherein cyclization can help improve these characteristics (see the art of record and, at least, Halai et al., 2011, Effects of Cyclization on Stability, Structure, and Activity of a-Conotoxin RgIA at the a9a10 Nicotinic Acetylcholine Receptor and GABAb Receptor, Journal of Medicinal Chemistry, 54: 6984-6992; additional references will be provided upon request). Therefore, one of skill in the art would look to cyclization methods to increase oral bioavailability, biological half-life, and stability of a-RgIA4 peptides and a-RgIA4 peptide analogs. The utilization of lactam bridges for cyclization is well-understood, routine, and conventional in the prior art. Additional reference will be provided upon request.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
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, 3, 5, 7, and 9-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 19-40, 47, and 53 of copending Application No. 18/567,010 in view of Iadonato et al. WO 2016/073949 published May 12, 2016; McIntosh WO 2014/194284 published December 4, 2014; and Schumann et al., 2002, Synthesis and biological activities of new side chain and backbone cyclic bradykinin analogues, J Peptide Res, 60: 128-140.
Copending Application No. 18/567,010 claims a-RgIA/conotoxin peptide analogs comprising DPR motifs and any amino acid at the C-terminus particularly Arg.
Iadonato et al. teach a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NO: 28 (100% identity except for the missing N-terminal Glu and C-terminal Lys of present SEQ ID NO: 12) wherein X can be Tyr, mono-iodo-tyrosine, or 3-iodo-tyrosine, and lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5). Iadonato et al. also teach SEQ ID NO: 5 which has the same length and 100% identity to present SEQ ID NOs: 17-19 (i.e. GCCTDPRCCit3-iodo-YQCY; see Table 1 wherein X11 is citrulline and X12 is 3-iodo-tyrosine).
RESULT 4
BCQ37026
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
ID BCQ37026 standard; peptide; 13 AA.
XX
AC BCQ37026;
XX
DT 30-JUN-2016 (first entry)
XX
DE Conus regius alpha-conotoxin RgIA analog peptide, SEQ ID:28.
XX
KW Alpha-conotoxin RgIA; analgesic; antiinflammatory; cancer;
KW chronic inflammation; endometriosis; fibromyalgia;
KW inflammatory bowel disease; inflammatory disease; metabolic disorder;
KW neuropathic pain; neuropathy; neuroprotective; pain; protein therapy;
KW sarcoidosis; sepsis; skin burns; therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Disulfide-bond 2..8
FT Disulfide-bond 3..12
FT Modified-site 10
FT /note= "3-iodo-Tyrosine"
FT Modified-site 13
FT /note= "C-terminal amide"
XX
CC PN WO2016073949-A1.
XX
CC PD 12-MAY-2016.
XX
CC PF 06-NOV-2015; 2015WO-US059613.
XX
PR 07-NOV-2014; 2014US-0123123P.
XX
CC PA (KINE-) KINETA THREE LLP.
XX
CC PI Iadonato SP, Munoz EJ;
XX
DR WPI; 2016-290272/35.
XX
CC PT New conotoxin peptide is alpha-9-alpha-10 subtype of nicotinic
CC PT acetylcholine receptor inhibitor, useful for treating a condition that is
CC PT pain, neuropathy, cancer, and inflammatory condition e.g. sepsis,
CC PT endometriosis and fibromyalgia.
XX
CC PS Example 1; SEQ ID NO 28; 58pp; English.
XX
CC The present invention relates to novel modified conotoxin analog peptides
CC or cone snail proteins (CSP) of alpha-conotoxin peptide RgIA derived from
CC predatory marine snails (e.g., Conus regius). The conotoxin analog
CC peptides block the alpha-9-alpha-10 subtype of the nicotinic
CC acetylcholine receptor (nAChR). The invention further discloses: (1) a
CC pharmaceutical composition comprising the conotoxin peptide and a
CC pharmaceutically acceptable salt; and (2) a method for treating at least
CC one condition associated with the alpha-9-alpha-10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject, which involves
CC administering to the subject a therapeutically effective amount of the
CC conotoxin peptide or the composition comprising the conotoxin peptide,
CC thereby treating the condition. The conotoxin peptide and pharmaceutical
CC composition of the invention are useful for treating at least one
CC condition associated with nAChR in a subject, where: the condition is
CC pain, an inflammatory condition or neuropathy; the pain includes general
CC pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain
CC and/or pain induced by peripheral nerve damage, inflammatory disorder, a
CC metabolic disorder, cancer, chemotherapy, surgical procedure or burn, or
CC cancer-related chronic pain and/or cancer-related neuropathy;
CC inflammatory condition comprises inflammation, chronic inflammation,
CC rheumatic disease, sepsis, fibromyalgia, inflammatory bowel disease,
CC sarcoidosis, endometriosis, uterine fibroids, an inflammatory skin
CC disease, an inflammatory condition of lungs, a disease associated with
CC inflammation of nervous system, periodontal disease or cardiovascular
CC disease; the inflammatory condition is mediated by immune cells, and the
CC inflammatory condition is long-term inflammation and peripheral
CC neuropathy following injury; and the condition is cancer. The present
CC sequence represents a Conus regius alpha-conotoxin RgIA analog peptide
CC which is used in preparing the pharmaceutical composition.
XX
SQ Sequence 13 AA;
Query Match 89.2%; Score 83; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCY 14
|||||||||||||
Db 1 GCCTDPRCRXQCY 13
McIntosh teaches a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NOs: 13 and 18 (100% identity except for the missing N-terminal Glu, Tyr instead of 3-iodo-tyrosine, and a C-terminal Arg instead of Lys of present SEQ ID NO: 12), utilizing mono-iodo-Tyr instead of Tyr to increase potency, conservative amino acid substitutions including Lys for Arg (i.e. C-terminal Lys), and adding an N-terminal pyroglutamate (i.e. conservative amino acid substitution for Glu) wherein the N-terminal pyroglutamate and the C-terminal Lys may form a lactam bridge to “protect” the disulfide cysteine bridges (please refer to the entire specification particularly the abstract; paragraphs 3-7, 13, 15-25, 28, 30-35, 45, 59, 100, 102; Table 1; claims). Please note: McIntosh also teaches sequences broader in scope than SEQ DI NOs: 13 and 18 (e.g. SEQ ID NO: 22, paragraph 17).
RESULT 2
BBR01953
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BBR01953 standard; peptide; 14 AA.
XX
AC BBR01953;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 18, SEQ ID 18.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 18; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 14 AA;
Query Match 91.4%; Score 85; Length 14;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
RESULT 3
BBR01948
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BBR01948 standard; peptide; 15 AA.
XX
AC BBR01948;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 13, SEQ ID 13.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 13; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 15 AA;
Query Match 91.4%; Score 85; Length 15;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
Schumann et al. teach that Glu can be added to the N-terminus and Lys can be added to the C-terminus to make lactam bridges (please refer to the entire reference particularly the abstract; Tables 1-3).
All the claimed elements (i.e. N-terminal Glu and C-terminal Lys to form a lactam bridge) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results 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. N-terminal pyroglutamate) for another (i.e. N-terminal Glu) would have yielded predictable results (i.e. cyclization of the peptide) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. N-terminal Glu and C-terminal Lys for lactam bridge formation) 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).
This is a provisional nonstatutory double patenting rejection.
Arguments and Response
Applicants’ arguments directed to the provisional rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over copending Application No. 18/567,010 in view of Iadonato et al.; McIntosh; and Schumann et al. for claims 1, 3, 5, 7, and 9-12 were considered but are not persuasive for the following reasons.
Applicants request that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of copending Application No. 18/567,010 in view of Iadonato et al.; McIntosh; and Schumann et al. renders obvious the a-RgIA/conotoxin peptide analogs 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, 3, 5, 7, and 9-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 9,717,775 in view of Iadonato et al. WO 2016/073949 published May 12, 2016; McIntosh WO 2014/194284 published December 4, 2014; and Schumann et al., 2002, Synthesis and biological activities of new side chain and backbone cyclic bradykinin analogues, J Peptide Res, 60: 128-140.
U.S. Patent 9,717,775 claim a-RgIA/conotoxin peptide analogs comprising DPR domains.
Iadonato et al. teach a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NO: 28 (100% identity except for the missing N-terminal Glu and C-terminal Lys of present SEQ ID NO: 12) wherein X can be Tyr, mono-iodo-tyrosine, or 3-iodo-tyrosine, and lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5). Iadonato et al. also teach SEQ ID NO: 5 which has the same length and 100% identity to present SEQ ID NOs: 17-19 (i.e. GCCTDPRCCit3-iodo-YQCY; see Table 1 wherein X11 is citrulline and X12 is 3-iodo-tyrosine).
RESULT 4
BCQ37026
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
ID BCQ37026 standard; peptide; 13 AA.
XX
AC BCQ37026;
XX
DT 30-JUN-2016 (first entry)
XX
DE Conus regius alpha-conotoxin RgIA analog peptide, SEQ ID:28.
XX
KW Alpha-conotoxin RgIA; analgesic; antiinflammatory; cancer;
KW chronic inflammation; endometriosis; fibromyalgia;
KW inflammatory bowel disease; inflammatory disease; metabolic disorder;
KW neuropathic pain; neuropathy; neuroprotective; pain; protein therapy;
KW sarcoidosis; sepsis; skin burns; therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Disulfide-bond 2..8
FT Disulfide-bond 3..12
FT Modified-site 10
FT /note= "3-iodo-Tyrosine"
FT Modified-site 13
FT /note= "C-terminal amide"
XX
CC PN WO2016073949-A1.
XX
CC PD 12-MAY-2016.
XX
CC PF 06-NOV-2015; 2015WO-US059613.
XX
PR 07-NOV-2014; 2014US-0123123P.
XX
CC PA (KINE-) KINETA THREE LLP.
XX
CC PI Iadonato SP, Munoz EJ;
XX
DR WPI; 2016-290272/35.
XX
CC PT New conotoxin peptide is alpha-9-alpha-10 subtype of nicotinic
CC PT acetylcholine receptor inhibitor, useful for treating a condition that is
CC PT pain, neuropathy, cancer, and inflammatory condition e.g. sepsis,
CC PT endometriosis and fibromyalgia.
XX
CC PS Example 1; SEQ ID NO 28; 58pp; English.
XX
CC The present invention relates to novel modified conotoxin analog peptides
CC or cone snail proteins (CSP) of alpha-conotoxin peptide RgIA derived from
CC predatory marine snails (e.g., Conus regius). The conotoxin analog
CC peptides block the alpha-9-alpha-10 subtype of the nicotinic
CC acetylcholine receptor (nAChR). The invention further discloses: (1) a
CC pharmaceutical composition comprising the conotoxin peptide and a
CC pharmaceutically acceptable salt; and (2) a method for treating at least
CC one condition associated with the alpha-9-alpha-10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject, which involves
CC administering to the subject a therapeutically effective amount of the
CC conotoxin peptide or the composition comprising the conotoxin peptide,
CC thereby treating the condition. The conotoxin peptide and pharmaceutical
CC composition of the invention are useful for treating at least one
CC condition associated with nAChR in a subject, where: the condition is
CC pain, an inflammatory condition or neuropathy; the pain includes general
CC pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain
CC and/or pain induced by peripheral nerve damage, inflammatory disorder, a
CC metabolic disorder, cancer, chemotherapy, surgical procedure or burn, or
CC cancer-related chronic pain and/or cancer-related neuropathy;
CC inflammatory condition comprises inflammation, chronic inflammation,
CC rheumatic disease, sepsis, fibromyalgia, inflammatory bowel disease,
CC sarcoidosis, endometriosis, uterine fibroids, an inflammatory skin
CC disease, an inflammatory condition of lungs, a disease associated with
CC inflammation of nervous system, periodontal disease or cardiovascular
CC disease; the inflammatory condition is mediated by immune cells, and the
CC inflammatory condition is long-term inflammation and peripheral
CC neuropathy following injury; and the condition is cancer. The present
CC sequence represents a Conus regius alpha-conotoxin RgIA analog peptide
CC which is used in preparing the pharmaceutical composition.
XX
SQ Sequence 13 AA;
Query Match 89.2%; Score 83; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCY 14
|||||||||||||
Db 1 GCCTDPRCRXQCY 13
McIntosh teaches a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NOs: 13 and 18 (100% identity except for the missing N-terminal Glu, Tyr instead of 3-iodo-tyrosine, and a C-terminal Arg instead of Lys of present SEQ ID NO: 12), utilizing mono-iodo-Tyr instead of Tyr to increase potency, conservative amino acid substitutions including Lys for Arg (i.e. C-terminal Lys), and adding an N-terminal pyroglutamate (i.e. conservative amino acid substitution for Glu) wherein the N-terminal pyroglutamate and the C-terminal Lys may form a lactam bridge to “protect” the disulfide cysteine bridges (please refer to the entire specification particularly the abstract; paragraphs 3-7, 13, 15-25, 28, 30-35, 45, 59, 100, 102; Table 1; claims). Please note: McIntosh also teaches sequences broader in scope than SEQ DI NOs: 13 and 18 (e.g. SEQ ID NO: 22, paragraph 17).
RESULT 2
BBR01953
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BBR01953 standard; peptide; 14 AA.
XX
AC BBR01953;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 18, SEQ ID 18.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 18; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 14 AA;
Query Match 91.4%; Score 85; Length 14;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
RESULT 3
BBR01948
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BBR01948 standard; peptide; 15 AA.
XX
AC BBR01948;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 13, SEQ ID 13.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 13; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 15 AA;
Query Match 91.4%; Score 85; Length 15;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
Schumann et al. teach that Glu can be added to the N-terminus and Lys can be added to the C-terminus to make lactam bridges (please refer to the entire reference particularly the abstract; Tables 1-3).
All the claimed elements (i.e. N-terminal Glu and C-terminal Lys to form a lactam bridge) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results 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. N-terminal pyroglutamate) for another (i.e. N-terminal Glu) would have yielded predictable results (i.e. cyclization of the peptide) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. N-terminal Glu and C-terminal Lys for lactam bridge formation) 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).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 9,717,775 in view of Iadonato et al.; McIntosh; and Schumann et al. for claims 1, 3, 5, 7, and 9-12 were considered but are not persuasive for the following reasons.
Applicants request that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 9,717,775 in view of Iadonato et al.; McIntosh; and Schumann et al. renders obvious the a-RgIA/conotoxin peptide analogs 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, 3, 5, 7, and 9-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9,284,358 in view of Iadonato et al. WO 2016/073949 published May 12, 2016; McIntosh WO 2014/194284 published December 4, 2014; and Schumann et al., 2002, Synthesis and biological activities of new side chain and backbone cyclic bradykinin analogues, J Peptide Res, 60: 128-140.
U.S. Patent 9,284,358 claim a-RgIA/conotoxin peptide analogs comprising DPR motifs a N-terminal pyroglutamic acid.
Iadonato et al. teach a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NO: 28 (100% identity except for the missing N-terminal Glu and C-terminal Lys of present SEQ ID NO: 12) wherein X can be Tyr, mono-iodo-tyrosine, or 3-iodo-tyrosine, and lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5). Iadonato et al. also teach SEQ ID NO: 5 which has the same length and 100% identity to present SEQ ID NOs: 17-19 (i.e. GCCTDPRCCit3-iodo-YQCY; see Table 1 wherein X11 is citrulline and X12 is 3-iodo-tyrosine).
RESULT 4
BCQ37026
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
ID BCQ37026 standard; peptide; 13 AA.
XX
AC BCQ37026;
XX
DT 30-JUN-2016 (first entry)
XX
DE Conus regius alpha-conotoxin RgIA analog peptide, SEQ ID:28.
XX
KW Alpha-conotoxin RgIA; analgesic; antiinflammatory; cancer;
KW chronic inflammation; endometriosis; fibromyalgia;
KW inflammatory bowel disease; inflammatory disease; metabolic disorder;
KW neuropathic pain; neuropathy; neuroprotective; pain; protein therapy;
KW sarcoidosis; sepsis; skin burns; therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Disulfide-bond 2..8
FT Disulfide-bond 3..12
FT Modified-site 10
FT /note= "3-iodo-Tyrosine"
FT Modified-site 13
FT /note= "C-terminal amide"
XX
CC PN WO2016073949-A1.
XX
CC PD 12-MAY-2016.
XX
CC PF 06-NOV-2015; 2015WO-US059613.
XX
PR 07-NOV-2014; 2014US-0123123P.
XX
CC PA (KINE-) KINETA THREE LLP.
XX
CC PI Iadonato SP, Munoz EJ;
XX
DR WPI; 2016-290272/35.
XX
CC PT New conotoxin peptide is alpha-9-alpha-10 subtype of nicotinic
CC PT acetylcholine receptor inhibitor, useful for treating a condition that is
CC PT pain, neuropathy, cancer, and inflammatory condition e.g. sepsis,
CC PT endometriosis and fibromyalgia.
XX
CC PS Example 1; SEQ ID NO 28; 58pp; English.
XX
CC The present invention relates to novel modified conotoxin analog peptides
CC or cone snail proteins (CSP) of alpha-conotoxin peptide RgIA derived from
CC predatory marine snails (e.g., Conus regius). The conotoxin analog
CC peptides block the alpha-9-alpha-10 subtype of the nicotinic
CC acetylcholine receptor (nAChR). The invention further discloses: (1) a
CC pharmaceutical composition comprising the conotoxin peptide and a
CC pharmaceutically acceptable salt; and (2) a method for treating at least
CC one condition associated with the alpha-9-alpha-10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject, which involves
CC administering to the subject a therapeutically effective amount of the
CC conotoxin peptide or the composition comprising the conotoxin peptide,
CC thereby treating the condition. The conotoxin peptide and pharmaceutical
CC composition of the invention are useful for treating at least one
CC condition associated with nAChR in a subject, where: the condition is
CC pain, an inflammatory condition or neuropathy; the pain includes general
CC pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain
CC and/or pain induced by peripheral nerve damage, inflammatory disorder, a
CC metabolic disorder, cancer, chemotherapy, surgical procedure or burn, or
CC cancer-related chronic pain and/or cancer-related neuropathy;
CC inflammatory condition comprises inflammation, chronic inflammation,
CC rheumatic disease, sepsis, fibromyalgia, inflammatory bowel disease,
CC sarcoidosis, endometriosis, uterine fibroids, an inflammatory skin
CC disease, an inflammatory condition of lungs, a disease associated with
CC inflammation of nervous system, periodontal disease or cardiovascular
CC disease; the inflammatory condition is mediated by immune cells, and the
CC inflammatory condition is long-term inflammation and peripheral
CC neuropathy following injury; and the condition is cancer. The present
CC sequence represents a Conus regius alpha-conotoxin RgIA analog peptide
CC which is used in preparing the pharmaceutical composition.
XX
SQ Sequence 13 AA;
Query Match 89.2%; Score 83; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCY 14
|||||||||||||
Db 1 GCCTDPRCRXQCY 13
McIntosh teaches a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NOs: 13 and 18 (100% identity except for the missing N-terminal Glu, Tyr instead of 3-iodo-tyrosine, and a C-terminal Arg instead of Lys of present SEQ ID NO: 12), utilizing mono-iodo-Tyr instead of Tyr to increase potency, conservative amino acid substitutions including Lys for Arg (i.e. C-terminal Lys), and adding an N-terminal pyroglutamate (i.e. conservative amino acid substitution for Glu) wherein the N-terminal pyroglutamate and the C-terminal Lys may form a lactam bridge to “protect” the disulfide cysteine bridges (please refer to the entire specification particularly the abstract; paragraphs 3-7, 13, 15-25, 28, 30-35, 45, 59, 100, 102; Table 1; claims). Please note: McIntosh also teaches sequences broader in scope than SEQ DI NOs: 13 and 18 (e.g. SEQ ID NO: 22, paragraph 17).
RESULT 2
BBR01953
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BBR01953 standard; peptide; 14 AA.
XX
AC BBR01953;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 18, SEQ ID 18.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 18; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 14 AA;
Query Match 91.4%; Score 85; Length 14;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
RESULT 3
BBR01948
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BBR01948 standard; peptide; 15 AA.
XX
AC BBR01948;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 13, SEQ ID 13.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 13; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 15 AA;
Query Match 91.4%; Score 85; Length 15;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
Schumann et al. teach that Glu can be added to the N-terminus and Lys can be added to the C-terminus to make lactam bridges (please refer to the entire reference particularly the abstract; Tables 1-3).
All the claimed elements (i.e. N-terminal Glu and C-terminal Lys to form a lactam bridge) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results 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. N-terminal pyroglutamate) for another (i.e. N-terminal Glu) would have yielded predictable results (i.e. cyclization of the peptide) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. N-terminal Glu and C-terminal Lys for lactam bridge formation) 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).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 9,284,358 in view of Iadonato et al.; McIntosh; and Schumann et al. for claims 1, 3, 5, 7, and 9-12 were considered but are not persuasive for the following reasons.
Applicants request that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 9,284,358 in view of Iadonato et al.; McIntosh; and Schumann et al. renders obvious the a-RgIA/conotoxin peptide analogs 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, 3, 5, 7, and 9-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,633,417 in view of Iadonato et al. WO 2016/073949 published May 12, 2016; McIntosh WO 2014/194284 published December 4, 2014; and Schumann et al., 2002, Synthesis and biological activities of new side chain and backbone cyclic bradykinin analogues, J Peptide Res, 60: 128-140.
U.S. Patent 10,633,417 claim a-RgIA/conotoxin peptide analogs comprising DPR motifs and C-terminal Arg.
Iadonato et al. teach a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NO: 28 (100% identity except for the missing N-terminal Glu and C-terminal Lys of present SEQ ID NO: 12) wherein X can be Tyr, mono-iodo-tyrosine, or 3-iodo-tyrosine, and lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5). Iadonato et al. also teach SEQ ID NO: 5 which has the same length and 100% identity to present SEQ ID NOs: 17-19 (i.e. GCCTDPRCCit3-iodo-YQCY; see Table 1 wherein X11 is citrulline and X12 is 3-iodo-tyrosine).
RESULT 4
BCQ37026
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
ID BCQ37026 standard; peptide; 13 AA.
XX
AC BCQ37026;
XX
DT 30-JUN-2016 (first entry)
XX
DE Conus regius alpha-conotoxin RgIA analog peptide, SEQ ID:28.
XX
KW Alpha-conotoxin RgIA; analgesic; antiinflammatory; cancer;
KW chronic inflammation; endometriosis; fibromyalgia;
KW inflammatory bowel disease; inflammatory disease; metabolic disorder;
KW neuropathic pain; neuropathy; neuroprotective; pain; protein therapy;
KW sarcoidosis; sepsis; skin burns; therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Disulfide-bond 2..8
FT Disulfide-bond 3..12
FT Modified-site 10
FT /note= "3-iodo-Tyrosine"
FT Modified-site 13
FT /note= "C-terminal amide"
XX
CC PN WO2016073949-A1.
XX
CC PD 12-MAY-2016.
XX
CC PF 06-NOV-2015; 2015WO-US059613.
XX
PR 07-NOV-2014; 2014US-0123123P.
XX
CC PA (KINE-) KINETA THREE LLP.
XX
CC PI Iadonato SP, Munoz EJ;
XX
DR WPI; 2016-290272/35.
XX
CC PT New conotoxin peptide is alpha-9-alpha-10 subtype of nicotinic
CC PT acetylcholine receptor inhibitor, useful for treating a condition that is
CC PT pain, neuropathy, cancer, and inflammatory condition e.g. sepsis,
CC PT endometriosis and fibromyalgia.
XX
CC PS Example 1; SEQ ID NO 28; 58pp; English.
XX
CC The present invention relates to novel modified conotoxin analog peptides
CC or cone snail proteins (CSP) of alpha-conotoxin peptide RgIA derived from
CC predatory marine snails (e.g., Conus regius). The conotoxin analog
CC peptides block the alpha-9-alpha-10 subtype of the nicotinic
CC acetylcholine receptor (nAChR). The invention further discloses: (1) a
CC pharmaceutical composition comprising the conotoxin peptide and a
CC pharmaceutically acceptable salt; and (2) a method for treating at least
CC one condition associated with the alpha-9-alpha-10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject, which involves
CC administering to the subject a therapeutically effective amount of the
CC conotoxin peptide or the composition comprising the conotoxin peptide,
CC thereby treating the condition. The conotoxin peptide and pharmaceutical
CC composition of the invention are useful for treating at least one
CC condition associated with nAChR in a subject, where: the condition is
CC pain, an inflammatory condition or neuropathy; the pain includes general
CC pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain
CC and/or pain induced by peripheral nerve damage, inflammatory disorder, a
CC metabolic disorder, cancer, chemotherapy, surgical procedure or burn, or
CC cancer-related chronic pain and/or cancer-related neuropathy;
CC inflammatory condition comprises inflammation, chronic inflammation,
CC rheumatic disease, sepsis, fibromyalgia, inflammatory bowel disease,
CC sarcoidosis, endometriosis, uterine fibroids, an inflammatory skin
CC disease, an inflammatory condition of lungs, a disease associated with
CC inflammation of nervous system, periodontal disease or cardiovascular
CC disease; the inflammatory condition is mediated by immune cells, and the
CC inflammatory condition is long-term inflammation and peripheral
CC neuropathy following injury; and the condition is cancer. The present
CC sequence represents a Conus regius alpha-conotoxin RgIA analog peptide
CC which is used in preparing the pharmaceutical composition.
XX
SQ Sequence 13 AA;
Query Match 89.2%; Score 83; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCY 14
|||||||||||||
Db 1 GCCTDPRCRXQCY 13
McIntosh teaches a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NOs: 13 and 18 (100% identity except for the missing N-terminal Glu, Tyr instead of 3-iodo-tyrosine, and a C-terminal Arg instead of Lys of present SEQ ID NO: 12), utilizing mono-iodo-Tyr instead of Tyr to increase potency, conservative amino acid substitutions including Lys for Arg (i.e. C-terminal Lys), and adding an N-terminal pyroglutamate (i.e. conservative amino acid substitution for Glu) wherein the N-terminal pyroglutamate and the C-terminal Lys may form a lactam bridge to “protect” the disulfide cysteine bridges (please refer to the entire specification particularly the abstract; paragraphs 3-7, 13, 15-25, 28, 30-35, 45, 59, 100, 102; Table 1; claims). Please note: McIntosh also teaches sequences broader in scope than SEQ DI NOs: 13 and 18 (e.g. SEQ ID NO: 22, paragraph 17).
RESULT 2
BBR01953
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BBR01953 standard; peptide; 14 AA.
XX
AC BBR01953;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 18, SEQ ID 18.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 18; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 14 AA;
Query Match 91.4%; Score 85; Length 14;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
RESULT 3
BBR01948
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BBR01948 standard; peptide; 15 AA.
XX
AC BBR01948;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 13, SEQ ID 13.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 13; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 15 AA;
Query Match 91.4%; Score 85; Length 15;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
Schumann et al. teach that Glu can be added to the N-terminus and Lys can be added to the C-terminus to make lactam bridges (please refer to the entire reference particularly the abstract; Tables 1-3).
All the claimed elements (i.e. N-terminal Glu and C-terminal Lys to form a lactam bridge) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results 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. N-terminal pyroglutamate) for another (i.e. N-terminal Glu) would have yielded predictable results (i.e. cyclization of the peptide) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. N-terminal Glu and C-terminal Lys for lactam bridge formation) 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).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 10,633,417 in view of Iadonato et al.; McIntosh; and Schumann et al. for claims 1, 3, 5, 7, and 9-12 were considered but are not persuasive for the following reasons.
Applicants request that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 10,633,417 in view of Iadonato et al.; McIntosh; and Schumann et al. renders obvious the a-RgIA/conotoxin peptide analogs 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, 3, 5, 7, and 9-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 9,469,674 in view of Iadonato et al. WO 2016/073949 published May 12, 2016; McIntosh WO 2014/194284 published December 4, 2014; and Schumann et al., 2002, Synthesis and biological activities of new side chain and backbone cyclic bradykinin analogues, J Peptide Res, 60: 128-140.
U.S. Patent 9,469,674 claim a-RgIA/conotoxin peptide analogs comprising DPR motifs.
Iadonato et al. teach a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NO: 28 (100% identity except for the missing N-terminal Glu and C-terminal Lys of present SEQ ID NO: 12) wherein X can be Tyr, mono-iodo-tyrosine, or 3-iodo-tyrosine, and lactam bridges between Glu and Lys (internal to the peptide but “protecting” a disulfide bridge between cysteines) and wherein a linker can be utilized to generate an N-terminus to C-terminus cyclized peptide (please refer to the entire specification particularly the abstract; paragraphs 2-6, 8, 12, 18-37, 39, 52, 53, 112, 113, 128, 152, 153, 156, 157; Tables 1-8; claims; Figures 3A-3D, 4, 5). Iadonato et al. also teach SEQ ID NO: 5 which has the same length and 100% identity to present SEQ ID NOs: 17-19 (i.e. GCCTDPRCCit3-iodo-YQCY; see Table 1 wherein X11 is citrulline and X12 is 3-iodo-tyrosine).
RESULT 4
BCQ37026
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
ID BCQ37026 standard; peptide; 13 AA.
XX
AC BCQ37026;
XX
DT 30-JUN-2016 (first entry)
XX
DE Conus regius alpha-conotoxin RgIA analog peptide, SEQ ID:28.
XX
KW Alpha-conotoxin RgIA; analgesic; antiinflammatory; cancer;
KW chronic inflammation; endometriosis; fibromyalgia;
KW inflammatory bowel disease; inflammatory disease; metabolic disorder;
KW neuropathic pain; neuropathy; neuroprotective; pain; protein therapy;
KW sarcoidosis; sepsis; skin burns; therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Disulfide-bond 2..8
FT Disulfide-bond 3..12
FT Modified-site 10
FT /note= "3-iodo-Tyrosine"
FT Modified-site 13
FT /note= "C-terminal amide"
XX
CC PN WO2016073949-A1.
XX
CC PD 12-MAY-2016.
XX
CC PF 06-NOV-2015; 2015WO-US059613.
XX
PR 07-NOV-2014; 2014US-0123123P.
XX
CC PA (KINE-) KINETA THREE LLP.
XX
CC PI Iadonato SP, Munoz EJ;
XX
DR WPI; 2016-290272/35.
XX
CC PT New conotoxin peptide is alpha-9-alpha-10 subtype of nicotinic
CC PT acetylcholine receptor inhibitor, useful for treating a condition that is
CC PT pain, neuropathy, cancer, and inflammatory condition e.g. sepsis,
CC PT endometriosis and fibromyalgia.
XX
CC PS Example 1; SEQ ID NO 28; 58pp; English.
XX
CC The present invention relates to novel modified conotoxin analog peptides
CC or cone snail proteins (CSP) of alpha-conotoxin peptide RgIA derived from
CC predatory marine snails (e.g., Conus regius). The conotoxin analog
CC peptides block the alpha-9-alpha-10 subtype of the nicotinic
CC acetylcholine receptor (nAChR). The invention further discloses: (1) a
CC pharmaceutical composition comprising the conotoxin peptide and a
CC pharmaceutically acceptable salt; and (2) a method for treating at least
CC one condition associated with the alpha-9-alpha-10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject, which involves
CC administering to the subject a therapeutically effective amount of the
CC conotoxin peptide or the composition comprising the conotoxin peptide,
CC thereby treating the condition. The conotoxin peptide and pharmaceutical
CC composition of the invention are useful for treating at least one
CC condition associated with nAChR in a subject, where: the condition is
CC pain, an inflammatory condition or neuropathy; the pain includes general
CC pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain
CC and/or pain induced by peripheral nerve damage, inflammatory disorder, a
CC metabolic disorder, cancer, chemotherapy, surgical procedure or burn, or
CC cancer-related chronic pain and/or cancer-related neuropathy;
CC inflammatory condition comprises inflammation, chronic inflammation,
CC rheumatic disease, sepsis, fibromyalgia, inflammatory bowel disease,
CC sarcoidosis, endometriosis, uterine fibroids, an inflammatory skin
CC disease, an inflammatory condition of lungs, a disease associated with
CC inflammation of nervous system, periodontal disease or cardiovascular
CC disease; the inflammatory condition is mediated by immune cells, and the
CC inflammatory condition is long-term inflammation and peripheral
CC neuropathy following injury; and the condition is cancer. The present
CC sequence represents a Conus regius alpha-conotoxin RgIA analog peptide
CC which is used in preparing the pharmaceutical composition.
XX
SQ Sequence 13 AA;
Query Match 89.2%; Score 83; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCY 14
|||||||||||||
Db 1 GCCTDPRCRXQCY 13
McIntosh teaches a-RgIA/conotoxin peptide analogs comprising DPR motifs, SEQ ID NOs: 13 and 18 (100% identity except for the missing N-terminal Glu, Tyr instead of 3-iodo-tyrosine, and a C-terminal Arg instead of Lys of present SEQ ID NO: 12), utilizing mono-iodo-Tyr instead of Tyr to increase potency, conservative amino acid substitutions including Lys for Arg (i.e. C-terminal Lys), and adding an N-terminal pyroglutamate (i.e. conservative amino acid substitution for Glu) wherein the N-terminal pyroglutamate and the C-terminal Lys may form a lactam bridge to “protect” the disulfide cysteine bridges (please refer to the entire specification particularly the abstract; paragraphs 3-7, 13, 15-25, 28, 30-35, 45, 59, 100, 102; Table 1; claims). Please note: McIntosh also teaches sequences broader in scope than SEQ DI NOs: 13 and 18 (e.g. SEQ ID NO: 22, paragraph 17).
RESULT 2
BBR01953
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BBR01953 standard; peptide; 14 AA.
XX
AC BBR01953;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 18, SEQ ID 18.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 18; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 14 AA;
Query Match 91.4%; Score 85; Length 14;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
RESULT 3
BBR01948
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BBR01948 standard; peptide; 15 AA.
XX
AC BBR01948;
XX
DT 29-JAN-2015 (first entry)
XX
DE Conus regius alpha-conotoxin peptide analog 13, SEQ ID 13.
XX
KW alpha-conotoxin; analgesic; antiinflammatory; breast tumor; cancer;
KW cancer pain; cardiovascular inflammation; cytostatic; dermatitis;
KW endometriosis; fibromyalgia; inflammatory bowel disease;
KW inflammatory disease; lung inflammation; mutein;
KW nervous system inflammation; neuropathic pain; neuropathy;
KW neuroprotective; pain; protein therapy; rheumatism; sarcoidosis; sepsis;
KW therapeutic; uterine fibroids.
XX
OS Conus regius.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 4
FT /note= "Wild-type Ser substituted by Thr"
FT Modified-site 10
FT /note= "Mono-iodo-tyrosine"
FT Misc-difference 11
FT /note= "Wild-type Arg substituted by Gln"
FT Misc-difference 13
FT /note= "Wild-type Arg substituted by Tyr"
XX
CC PN WO2014194284-A1.
XX
CC PD 04-DEC-2014.
XX
CC PF 30-MAY-2014; 2014WO-US040374.
XX
PR 31-MAY-2013; 2013US-0829633P.
PR 05-JUL-2013; 2013US-0843135P.
XX
CC PA (MCIN/) MCINTOSH J M.
XX
CC PI Mcintosh JM;
XX
DR WPI; 2014-V55529/01.
XX
CC PT New conotoxin peptide, useful for treating conditions associated with
CC PT alpha9alpha10 subtype of the nicotinic acetylcholine receptor such as
CC PT pain, inflammatory conditions, inflammation, and/or cancer.
XX
CC PS Claim 3; SEQ ID NO 13; 60pp; English.
XX
CC The present invention relates to a novel conotoxin peptide and its
CC applications. Also described are: (1) a pharmaceutical composition
CC comprising the conotoxin peptide; and (2) a method for treating at least
CC one condition associated with the alpha 9 alpha 10 subtype of the
CC nicotinic acetylcholine receptor (nAChR) in a subject by administering
CC the conotoxin peptide or the pharmaceutical composition. The composition
CC and peptide are used for treating pain (such as general pain, chronic
CC pain, neuropathic pain, nociceptive pain, inflammatory pain, pain induced
CC by peripheral nerve damage, pain induced by an inflammatory disorder,
CC pain induced by a metabolic disorder, pain induced by cancer, pain
CC induced by chemotherapy, pain induced by a surgical procedure, and/or
CC pain induced by a burn, and chemotherapy-related chronic pain and/or
CC chemotherapy-related neuropathy), inflammatory condition (such as chronic
CC inflammation, rheumatic disease, sepsis, fibromyalgia, inflammatory bowel
CC disease, sarcoidosis, endometriosis, uterine fibroids, an inflammatory
CC skin disease, an inflammatory condition of the lungs, a disease
CC associated with inflammation of the nervous system, periodontal disease
CC or cardiovascular disease), neuropathy and cancer (breast cancer). The
CC present sequence is a Conus regius alpha-conotoxin peptide analog of SEQ
CC ID NO: 1 (BBR01936), used in the invention for treating pain,
CC inflammation and breast cancer.
XX
SQ Sequence 15 AA;
Query Match 91.4%; Score 85; Length 15;
Best Local Similarity 85.7%;
Matches 12; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GCCTDPRCRXQCYK 15
|||||||||:|||:
Db 1 GCCTDPRCRYQCYR 14
Schumann et al. teach that Glu can be added to the N-terminus and Lys can be added to the C-terminus to make lactam bridges (please refer to the entire reference particularly the abstract; Tables 1-3).
All the claimed elements (i.e. N-terminal Glu and C-terminal Lys to form a lactam bridge) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results 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. N-terminal pyroglutamate) for another (i.e. N-terminal Glu) would have yielded predictable results (i.e. cyclization of the peptide) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. N-terminal Glu and C-terminal Lys for lactam bridge formation) 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).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 9,469,674 in view of Iadonato et al.; McIntosh; and Schumann et al. for claims 1, 3, 5, 7, and 9-12 were considered but are not persuasive for the following reasons.
Applicants request that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 9,469,674 in view of Iadonato et al.; McIntosh and Schumann et al. renders obvious the a-RgIA/conotoxin peptide analogs 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.
Taylor, 2002, The Synthesis and Study of Side-Chain Lactam-Bridged Peptides, Biopolymers, 66: 49-75.
U.S. Patents 6,172,041; 6,277,825; 6,399,574; 6,515,103; and 9,718,864.
Future Communications
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/AMBER D STEELE/Primary Examiner, Art Unit 1658
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