DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of SEQ ID NO:45, SEQ ID NO:3 and Serotype A in the reply filed on 6/25/2026 is acknowledged. The traversal is on the ground(s) that the proteins share a common structure comprising a light chain and operate under the same mechanism. Applicants do however state that the species differ in the type of toxin and structural variations. This is not found persuasive because as acknowledged by applicant and as presented in the Species Election, the species of Group A lack unity of invention because they do not share the same or corresponding technical feature, for example the amino acid sequences of SEQ ID NO:31-58 are different. The same is true for the sequences of Group B and the serotypes of Group C.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-10, 17 are pending and have been considered on the merits herein.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
It is noted that neither of the certified priority documents are in English.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-10, 17 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Lee et al. (US10300118).
Regarding claim 1, Lee teaches a method of treating pain comprising administering a therapeutically effective amount of a composition comprising a botulinum toxin recombinant protein, wherein the recombinant protein has a cell penetrating peptide fused to the light chain of the botulinum toxin (abstract, col. 1, lines 17-21, col. 9, lines 33-38). The composition is for transdermal delivery of the cell penetrating botulinum toxin recombinant protein used to treat the skin (abstract, col. 3, lines 51-col. 4, lines 1-4, col. 7, lines 35-42). The cell penetrating peptide consists of the amino acid sequence of SEQ ID NO:1 (see SEQ ID NO:1 of Lee).
Query Match 100.0%; Score 69; Length 13;
Best Local Similarity 100.0%; Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KAMININKFLNQC 13
|||||||||||||
Db 1 KAMININKFLNQC 13
Regarding claim 2, the botulinum toxin recombinant protein consists of the amino acid sequence of SEQ ID NO:45 (see SEQ ID NO:45 of Lee).
OTHER INFORMATION: TD1-BoNT/A Light chain Amino Acid Sequence with hexahistidine
Query Match 100.0%; Score 2480; Length 469;
Best Local Similarity 100.0%;
Matches 469; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKAMININKFLNQCPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKAMININKFLNQCPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPE 60
Qy 61 RDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRML 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRML 120
Qy 121 LTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKS 180
Qy 181 FGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 FGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIH 240
Qy 241 AGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYY 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYY 300
Qy 301 NKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 NKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTE 360
Qy 361 IYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTE 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 IYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTE 420
Qy 421 INNMNFTKLKNFTGLFEFYKLLCVRGIITSKTKSLDKGYNKLEHHHHHH 469
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 INNMNFTKLKNFTGLFEFYKLLCVRGIITSKTKSLDKGYNKLEHHHHHH 469
Regarding claim 3, the botulinum toxin light chain consists of the amino acid sequence of SEQ ID NO:3 (SEQ ID NO:17, 38, 52).
OTHER INFORMATION: BoNT/A Light chain Amino Acid Sequence with hexahistidine
Query Match 100.0%; Score 2354; Length 468;
Best Local Similarity 100.0%;
Matches 448; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN 80
Qy 61 PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG 140
Qy 121 STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY 200
Qy 181 GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN 260
Qy 241 RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 261 RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA 320
Qy 301 KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 321 KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV 380
Qy 361 LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 381 LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT 440
Qy 421 GLFEFYKLLCVRGIITSKTKSLDKGYNK 448
||||||||||||||||||||||||||||
Db 441 GLFEFYKLLCVRGIITSKTKSLDKGYNK 468
Regarding claim 4, the botulinum toxin light chain further includes a hexahistidine tag at one end (col. 9, lines 63, 64, and SEQ ID NO:17 and 52 as seen above).
Regarding claim 5, the botulinum toxin light chain is selected from serotypes A, B, C, D, E, F, and G (col. 9, lines 58-60).
Regarding claim 6, the cell penetrating peptide is fused to a carboxyl, an amino terminus (col. 8, lines 62-65, col. 9, lines 33-52).
Regarding claim 7, the fusion is achieved by a peptide bond or a covalent bond (col. 9, lines 39-43).
Regarding claim 8, the protein relieves muscle tension as it treats migraines (col. 5, line 4, for example).
Regarding claim 9, the pain to be treated includes migraines, physical pain as it treats dystonia, torticollis, temporomandibular disorder, facial and eyelid spasms, for example (col. 5, lines 18-35, 50).
Regarding claim 10, the composition is for transdermal administration (col. 5, lines 5-7, 22-23, col. 6, lines 1-7, for example)
Regarding claim 17, the composition is a pharmaceutical composition (col. 5, lines 5-7) or cosmetic composition (col. 5, lines 11-13).
Thus, the reference anticipates the claimed subject matter.
Claim(s) 1, 3-10, 17 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Collier et al. (US20180251740).
Collier teaches a method of treating pain comprising administering a composition comprising a fusion protein comtaining a botulinum toxin recombinant protein and a cell-penetrating peptide consisting of the amino acid sequence of SEQ ID NO:1 fused to the end or both ends of a botulinum toxin light chain (abstract, 0004-0006, 0099).
Regarding claims 1, 3, the cell-penetrating peptide consists of the amino acid sequence of SEQ ID NO:1 and contains the botulinum light chain of SEQ ID NO:3. See Collier SEQ ID NO:20, 30. (0210).
Query Match 100.0%; Score 69; Length 842;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KAMININKFLNQC 13
|||||||||||||
Db 779 KAMININKFLNQC 791
Query Match 99.8%; Score 2350; Length 448;
Best Local Similarity 99.8%;
Matches 447; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN 60
|||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||
Db 1 MPFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN 60
Qy 61 PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG 120
Qy 121 STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY 180
Qy 181 GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN 240
Qy 241 RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA 300
Qy 301 KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV 360
Qy 361 LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT 420
Qy 421 GLFEFYKLLCVRGIITSKTKSLDKGYNK 448
||||||||||||||||||||||||||||
Db 421 GLFEFYKLLCVRGIITSKTKSLDKGYNK 448
Regarding claim 4, the light chain includes a hexahistidine tag, i.e., HHHHHH (SEQ ID NO:61, 0305)
Regarding claim 5, the botulinum toxin light chain is from serotypes, A-G (0210, for example).
Regarding claim 6, the peptide is fused to at least the N or C-terminus (0199, 0207).
Regarding claim 7, the fusion is by a peptide bond (0199).
Regarding claims 8 and 9, the relieves muscle tension and the pain is chronic pain, diabetic neuropathy, fibromyalgia, pain disorders, cancer pain and nociception (0004-0006, 0099, 0101, 0102).
Regarding claim 10, the composition is for transdermal administration (0424).
Regarding claim 17, the composition is a pharmaceutical composition (0116, for example).
Thus, the reference anticipates the claimed subject matter.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIFFANY M GOUGH/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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