Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims/Rejections
Applicants remark file 09/12/25 regarding the objections to a sequence listing and the obviousness type double patenting rejection were found unpersuasive and will be addressed below. Claims 82-103 are pending and under examination.
Restriction/Election
Applicant’s election with partial traverse of group I, claims 82 and 87-104, in the reply filed on 01/28/25 is acknowledged. Applicants partially traversed the restriction, and assert that Group I should include claims 82 and 87-104 rather than 82 and 97-104, which was found persuasive.
Claims 83-86 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/28/25.
Claims 82 and 87-104 were searched an found to be free of the prior art insofar as the sequences could be searched as defined in the sequence listing, as will be discussed in the below objections.
Objections
Claims objected to because of the following informalities: The claims are drawn to SEQ ID NOs: 1, 4, 6-9, 12, 14-16 and 76, which comes up as undefined in the sequence listing. Appropriate correction is required.
The disclosure is objected to because of the following informalities: The XML listings for SEQ ID NOs: 1, 4, 6-9, 12, 14-16 and 76 come up as undefined. A replacement sequence listing in a readable XML format for these sequences must be provided in order to comply with the sequence listing rules and to provide a searchable reference sequence for each SEQ ID NO in ABSS/SCORE.
In addition to the previous claim objections, sequences of claim 1: fftky, ffgkf, ftfcy, ffgcy, ffgcf all comprise 5 specifically defined amino acids, thus requiring a sequence identifier.
Additionally, where there are four or more specifically defined amino acids, as there are in claim 104 and in the specification at [0070, 0128], a sequence identified is required.
Response to Arguments/Remarks
Applicants have responded that according to 37 CFR 1.831(b)(1), patent applications disclosing amino acid sequences and/or nucleotide sequences must have a computer readable Sequence Listing in XML format for "[a]n unbranched sequence or linear region of a branched sequence containing 4 or more specifically defined amino acids," or "[a]n unbranched sequence or linear region of a branched sequence of 10 or more specifically defined nucleotides," where "specifically defined" is defined in paragraph 3(k) of the WIPO Standard ST.26 Manual to mean "any amino acid than other those represented by the symbol "X" and "any nucleotide other than those represented by the symbol "n." SEQ ID NOs: 1, 4, 6- 9, 12, and 14-16 contain modified amino acids that are defined as "X", and thus are not unbranched sequences or linear regions of a branched sequence containing 4 or more specifically defined amino acids. SEQ ID NO: 76 contains modified nucleotides that are defined as "n," and thus are not unbranched sequences or linear regions of a branched sequence of 10 or more.
Regarding the ST.26 rules, although, the ST.26 manual does state that where a peptide is represented by “X” and has less than 4 specifically defined amino acids is not required to be in the listing, where it is a linear sequence of a branched peptide. However, the peptides, as defined in the specification are not represented by X and the peptides in the claims not recited as X.
The specification states that the sequences of claim 1 are listed as follows: napthylacetyl-FFKY (SEQ ID NO: 1), napthylacetyl-FFFKY (SEQ ID NO: 2), napthylacetyl-FFGKY (SEQ ID NO: 3), napthylacetyl-FFGK (SEQ ID NO: 4), napthylacetyl-FFGKF (SEQ ID NO: 5), napthylacetyl-ftky, napthylacetyl-fftky, napthylacetyl-ffgky, napthylacetyl-ffgk, napthylacetyl-ffgkf, napthylacetyl-FFK(Dmt) (SEQ ID NO: 6), napthylacetyl-FFFK(Dmt) (SEQ ID NO: 7), napthylacetyl-FFGK(Dmt) (SEQ ID NO: 8), napthylacetyl-ftk(dmt), napthylacetyl-fftk(dmt), napthylacetyl-ffgk(dmt), napthylacetyl-FFCY (SEQ ID NO: 9), napthylacetyl-FFFCY (SEQ ID NO: 10), napthylacetyl-FFGCY (SEQ ID NO: 11), napthylacetyl-FFGC (SEQ ID NO: 12), napthylacetyl-FFGCF (SEQ ID NO: 13), napthylacetyl-ffcy, napthylacetyl-ftfcy, napthylacetyl-ffgcy, napthylacetyl-ffge, napthylacetyl-ffgcf, napthylacetyl-FFC(Dmt) (SEQ ID NO: 14), napthylacetyl-FFFC(Dmt) (SEQ ID NO: 15), napthylacetyl-FFGC(Dmt) (SEQ ID NO: 16), napthylacetyl-ffc(dmt), napthylacetyl-fffc(dmt), napthylacetyl-ffgc(dmt), where Dmt is 2,6-dimethyl-L-tyrosine and dmt is 2,6-dimethyl-D-tyrosine [0063].
The claims do not recite napthylacetyl, and the SEQ ID NOs of the specification do not define them as “X,” but as the first residue of the sequence, “F.” The sequence listing is intended to standardize these sequences, and here the claims, specification and listing are not consistent with the rules of ST.26 for specifically defined amino acids. The sequences listing defines the first residue as “X”, which is not congruent with the listing rules.
ST.26 states: “A modified amino acid must be further described in the feature table (see paragraph 60 et seq.). Where applicable, the feature keys “CARBOHYD” or “LIPID” should be used together with the qualifier “note”. The feature key “MOD_RES” should be used for other post-translationally modified amino acids together with the qualifier “note”; otherwise the feature key “SITE” together with the qualifier “note” should be used. The value for the qualifier “note” must either be an abbreviation set forth in Annex I (see Section 4, Table 4), or the complete, unabbreviated name of the modified amino acid. The abbreviations set forth in Table 4 referred to above or the complete, unabbreviated names must not be used in the sequence itself.” (p. 3.26.vi 59, ST.26, WIPO Handbook on Intellectual Property Information and Documentation).
Although the first residue is modified by napthylacetyl, it is attached to the specifically defined phenylalanine. For reference, see specifically examples 7.16 and 7.18, p. 3.26.i.47, which refer to similar modified residues. Here, the Claimed Phenylalanine residues are not X in that they can be alternative residues, they are specifically defined, but they have a napthylacetyl group attached to the C-terminus, meaning SEQ ID NOs: 1-16 all have four defined amino acids, as discussed above and as can be seen in the claims and specification.
Here, applicants have described the first phenylalanine as F in the claims, but as X in the sequence listing, which does not comply with ST.26. As this is a complex sequence listing issue and the rules have changed to ST.26 from ST.25 in the parent application, please request an Examiner interview to discuss and resolve the issue, seek guidance from the USPTO sequence help desk at 571-272-2510 or email SequenceHelpDesk@uspto.gov.
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 82 and 87-104 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,191,724 in view of Gron et al. (US2008/0268015). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims teach the following:
1. A branched peptide comprising: a first peptide chain and a second peptide chain having its C-terminal amino acid covalently linked to a sidechain of an amino acid residue of the first peptide chain, wherein the first peptide chain comprises a plurality of aromatic amino acids and an aromatic group linked to an amino terminus of the first peptide chain, and comprises the amino acid sequence of napthylacetyl-FFKY (SEQ ID NO: 1), napthylacetyl-FFFKY (SEQ ID NO: 2), napthylacetyl-FFGKY (SEQ ID NO: 3), napthylacetyl-FFGK (SEQ ID NO: 4), FFGKF (SEQ ID NO: 5), napthylacetyl-ffky, napthylacetyl-fffky, napthylacetyl-ffgky, napthylacetyl-ffgk, napthylacetyl-ffgkf, napthylacetyl-FFK(Dmt) (SEQ ID NO: 6), napthylacetyl-FFFK(Dmt) (SEQ ID NO: 7), napthylacetyl-FFGK(Dmt) (SEQ ID NO: 8), napthylacetyl-ffk(dmt), napthylacetyl-fffk(dmt), napthylacetyl-ffgk(dmt), napthylacetyl-FFCY (SEQ ID NO: 9), napthylacetyl-FFFCY (SEQ ID NO: 10), napthylacetyl-FFGCY (SEQ ID NO: 11), napthylacetyl-FFGC (SEQ ID NO: 12), napthylacetyl-FFGCF (SEQ ID NO: 13), napthylacetyl-ffcy, napthylacetyl-fffcy, napthylacetyl-ffgcy, napthylacetyl-ffgc, napthylacetyl-ffgcf, napthylacetyl-FFC(Dmt) (SEQ ID NO: 14), napthylacetyl-FFFC(Dmt) (SEQ ID NO: 15), napthylacetyl-FFGC(Dmt) (SEQ ID NO: 16), napthylacetyl-ffc(dmt), napthylacetyl-fffc(dmt), or napthylacetyl-ffgc(dmt), wherein Dmt is 2,6-dimethyl-L-tyrosine and dmt is 2,6-dimethyl-D-tyrosine; and wherein the second peptide chain comprises a plurality of hydrophilic amino acids and an enzyme cleavage site, and comprises the amino acid sequence of DDDDK (SEQ ID NO: 17), KDDDK (SEQ ID NO: 18), DDDDR (SEQ ID NO: 19), KDDDR (SEQ ID NO: 20), DADDK (SEQ ID NO: 21), KADDK (SEQ ID NO: 22), DADDR (SEQ ID NO: 23), KADDR (SEQ ID NO: 24), DEDDK (SEQ ID NO: 25), KEDDK (SEQ ID NO: 26), DEDDR (SEQ ID NO: 27), KEDDR (SEQ ID NO: 28), EDDDK (SEQ ID NO: 29), EDDDR (SEQ ID NO: 30), EEDDK (SEQ ID NO: 31), EEDDR (SEQ ID NO: 32), DLYDDDDK (SEQ ID NO: 33), DLYDDDDR (SEQ ID NO: 34), DYKDDDDK (SEQ ID NO: 35), DYKDDDDR (SEQ ID NO: 36), DYKDADDK (SEQ ID NO: 37), DYKDADDR (SEQ ID NO: 38), DYKDEDDK (SEQ ID NO: #39), DYKDEDDR (SEQ ID NO: 40), DYKEDDDK (SEQ ID NO: 41), DYKEDDDR (SEQ ID NO: 42), DYKEEDDK (SEQ ID NO: 43), DYKEEDDR (SEQ ID NO: 44), or LKGDR (SEQ ID NO: 45).
2. The branched peptide according to claim 1, wherein the plurality of aromatic amino acids are selected from the group consisting of phenylalanine, tyrosine, and tryptophan.
3. The branched peptide according to claim 1, wherein the amino acid residue having the sidechain covalently linked to the C-terminal amino acid of the second peptide chain is: (i) Lys, and the covalent bond is —NH—C(O)—; or (ii) Cys, and the covalent bond is —S—C(O)—.
4. The branched peptide according to claim 1, wherein the first peptide is less than 20 amino acids in length.
5. The branched peptide according to claim 1, wherein the branched peptide is capable of forming micelle structures in an aqueous medium and, following enzymatic cleavage of the second peptide chain at the enzyme cleavage site, is capable of self-assembling to form a hydrogel in an aqueous medium.
6. The branched peptide according to claim 1, wherein the first peptide chain is selected from the group consisting of napthylacetyl-FFKY (SEQ ID NO: 1), napthylacetyl-FFFKY (SEQ ID NO: 2), napthylacetyl-FFGKY (SEQ ID NO: 3), napthylacetyl-FFGK (SEQ ID NO: 4), napthylacetyl-FFGKF (SEQ ID NO: 5), napthylacetyl-ffky, napthylacetyl-fffky, napthylacetyl-ffgky, napthylacetyl-ffgk, napthylacetyl-ffgkf, napthylacetyl-FFK(Dmt) (SEQ ID NO: 6), napthylacetyl-FFFK(Dmt) (SEQ ID NO: 7), napthylacetyl-FFGK(Dmt) (SEQ ID NO: 8), napthylacetyl-ffk(dmt), napthylacetyl-fffk(dmt), napthylacetyl-ffgk(dmt), wherein Dmt is 2,6-dimethyl-L-tyrosine and dmt is 2,6-dimethyl-D-tyrosine.
7. The branched peptide according to claim 1, wherein the second peptide chain comprises not more than 50 amino acid residues between the enzyme cleavage site and the covalent bond.
8. The branched peptide according to claim 1, wherein the second peptide chain comprises an enterokinase cleavage site.
9. The branched peptide according to claim 7, wherein the second peptide chain comprises a single amino acid residue between the cleavage site and the covalent bond, where the single amino acid is other than Trp or Pro.
10. The branched peptide according to claim 1, wherein the second peptide chain comprises the amino acid sequence of DDDDK (SEQ ID NO: 17), KDDDK (SEQ ID NO: 18), DDDDR (SEQ ID NO: 19), KDDDR (SEQ ID NO: 20), DYKDDDDK (SEQ ID NO: 35), or DYKDDDDR (SEQ ID NO: 36).
11. The branched peptide according to claim 1, wherein the second peptide chain comprising the amino acid sequence of SEQ ID NO: 17 is DDDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 46), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 18 is KDDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 47), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 19 is DDDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 48), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 20 is KDDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 49), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 21 is DADDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 50), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 22 is KADDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 51), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 23 is DADDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 52), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 24 is KADDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 53), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 25 is DEDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 54), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 26 is KEDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 55), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 27 is DEDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 56), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 28 is KEDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 57), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 29 is EDDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 58), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 30 is EDDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 59), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 31 is EEDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 60), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 32 is EEDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 61), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 33 is DLYDDDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 62), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 34 is DLYDDDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 63), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 35 is DYKDDDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 64), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 36 is DYKDDDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 65), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 37 is DYKDADDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 66), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 38 is DYKDADDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 67), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 39 is DYKDEDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 68), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 40 is DYKDEDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 69), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 41 is DYKEDDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 70), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 42 is DYKEDDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 71), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 43 is DYKEEDDK(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 72), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 44 is DYKEEDDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 73), or the second peptide chain comprising the amino acid sequence of SEQ ID NO: 45 is LKGDR(G/A/T/S/Y/H/Q/E/N/D/R/K) (SEQ ID NO: 74).
12. A branched peptide comprising a first peptide chain and a second peptide chain having its C-terminal amino acid covalently linked to a sidechain of a lysine residue of the first peptide chain wherein the branched peptide is selected from the group consisting of: Nap-FFK(.sup.εG-KDDDDKYD-NH.sub.2)Y, Nap-ffk(.sup.εG-KDDDDKYD-NH.sub.2)y, Nap-FFK(.sup.εG-RDDDDKYD-NH.sub.2)Y, Nap-ffk(.sup.εG-RDDDDKYD-NH.sub.2)y, Nap-FFK(.sup.εG-KDDDDKYD-NH.sub.2)(Dmt), Nap-ffk(.sup.εG-KDDDDKYD-NH.sub.2)(dmt), Nap-FFK(.sup.εG-RDDDDKYD-NH.sub.2)(Dmt), Nap-ffk(.sup.εG-RDDDDKYD-NH.sub.2)(dmt), Nap-FFK(.sup.εG-KDDDDK(DmOD-NH.sub.2)Y, Nap-ffk(.sup.εG-KDDDDK(DmOD-NH.sub.2)y, Nap-FFK(.sup.εG-RDDDDK(DmOD-NH.sub.2)Y, Nap-ffk(.sup.εG-RDDDDK(DmOD-NH.sub.2)y, Nap-FFK(.sup.εG-KDDDDK(DmOD-NH.sub.2)(Dmt), Nap-ffk(.sup.εG-KDDDDK(DmOD-NH.sub.2)(dmt), Nap-FFK(.sup.εG-RDDDDK(DmOD-NH.sub.2)(Dmt), Nap-ffk(.sup.εG-RDDDDK(DmOD-NH.sub.2)(dmt), Nap-FFK(.sup.εG-KDDDDKYD-NH.sub.2)Y—Z, Nap-ffk(.sup.εG-KDDDDKYD-NH.sub.2)y-Z, Nap-FFK(.sup.εG-RDDDDKYD-NH.sub.2)Y—Z, Nap-ffk(.sup.εG-RDDDDKYD-NH.sub.2)y-Z, Nap-FFK(.sup.εG-KDDDDKYD-NH.sub.2)(Dmt)-Z, Nap-ffk(.sup.εG-KDDDDKYD-NH.sub.2)(dmt)-Z, Nap-FFK(.sup.ε-RDDDDKYD-NH.sub.2)(Dmt)-Z, Nap-ffk(.sup.εG-RDDDDKYD-NH.sub.2)(dmt)-Z, Nap-FFK(.sup.εG-KDDDDK(DmOD-NH.sub.2)Y—Z, Nap-ffk(.sup.ε-KDDDDK(DmOD-NH.sub.2)y-Z, Nap-FFK(.sup.εG-RDDDDK(DmOD-NH.sub.2)Y—Z, Nap-ffk(.sup.εG-RDDDDK(DmOD-NH.sub.2)y-Z, Nap-FFK(.sup.εG-KDDDDK(DmOD-NH.sub.2)(Dmt)-Z, Nap-ffk(.sup.εG-KDDDDK(DmOD-NH.sub.2)(dmt)-Z, Nap-FFK(.sup.εG-RDDDDK(DmOD-NH.sub.2)(Dmt)-Z, Nap-ffk(.sup.εG-RDDDDK(DmOD-NH.sub.2)(dmt)-Z, wherein the lowercase letters denote D-amino acids and the uppercase letters denote L-amino acids, wherein Nap is napthylacetyl, wherein Z is a therapeutic agent covalently bonded to the C-terminal residue of the first peptide chain, and wherein Dmt is 2,6-dimethyl-L-tyrosine and dmt is 2,6-dimethyl-D-tyrosine.
13. The branched peptide according to claim 1, wherein the first peptide chain further comprises a therapeutic agent, Z, covalently bonded to the C-terminal residue of first peptide chain.
14. The branched peptide according to claim 13, wherein the therapeutic agent, Z, is selected from the group consisting of antioxidants, coenzymes, vitamins, metabolites, analgesics, anti-inflammatory agents, antihelminthics, anti-arrhythmic agents, anti-bacterial agents, anti-viral agents, anti-coagulants, anti-depressants, anti-diabetics, anti-epileptics, anti-fungal agents, anti-gout agents, anti-hypertensive agents, anti-thrombogenic agents, anti-claudication agents, anti-atherosclerotic drugs, vascular agents, anti-malarials, anti-migraine agents, anti-muscarinic agents, anti-neoplastic agents, erectile dysfunction improvement agents, immunosuppressants, anti-protozoal agents, anti-thyroid agents, anxiolytic agents, sedatives, hypnotics, neuroleptics, β-blockers, cardiac inotropic agents, corticosteroids, diuretics, anti-parkinsonian agents, gastro-intestinal agents, histamine receptor antagonists, keratolyptics, lipid regulating agents, anti-anginal agents, Cox-2 inhibitors, leukotriene inhibitors, macrolides, muscle relaxants, nutritional agents, opioid analgesics, protease inhibitors, sex hormones, stimulants, anti-osteoporosis agents, anti-obesity agents, cognition enhancers, anti-urinary incontinence agents, anti-benign prostate hypertrophy agents, essential fatty acids, non-essential fatty acids, cytokines, growth factors, antibodies, radioprotective agents, and cardioprotective agents.
15. A pharmaceutical composition comprising the branched peptide according to claim 1 in an aqueous medium.
16. The pharmaceutical composition according to claim 15, wherein the branched peptides form micelle structures.
17. The pharmaceutical composition according to claim 16 further comprising a therapeutic agent encapsulated within micelle structures.
18. The pharmaceutical composition according to claim 17, wherein the therapeutic agent is selected from the group consisting of analgesics, anti-inflammatory agents, antihelminthics, anti-arrhythmic agents, anti-bacterial agents, anti-viral agents, anti-coagulants, anti-depressants, anti-diabetics, anti-epileptics, anti-fungal agents, anti-gout agents, anti-hypertensive agents, anti-thrombogenic agents, anti-claudication agents, anti-atherosclerotic drugs, vascular agents, anti-malarials, anti-migraine agents, anti-muscarinic agents, anti-neoplastic agents (e.g., antiproliferative or chemotherapeutic agents), erectile dysfunction improvement agents, immunosuppressants, anti-protozoal agents, anti-thyroid agents, anxiolytic agents, sedatives, hypnotics, neuroleptics, β-blockers, cardiac inotropic agents, corticosteroids, diuretics, anti-parkinsonian agents, gastro-intestinal agents, histamine receptor antagonists, keratolyptics, lipid regulating agents, anti-anginal agents, Cox-2 inhibitors, leukotriene inhibitors, macrolides, muscle relaxants, nutritional agents, opioid analgesics, protease inhibitors, sex hormones, stimulants, anti-osteoporosis agents, anti-obesity agents, cognition enhancers, anti-urinary incontinence agents, anti-benign prostate hypertrophy agents, essential fatty acids, non-essential fatty acids, antioxidants, and mixtures thereof.
19. A method of delivering a therapeutic agent into mitochondria comprising: encapsulating a therapeutic agent within a micelle structure of a pharmaceutical composition according to claim 15; and contacting a cell with the pharmaceutical composition, whereby micelle structures are taken up by the cell and targeted to mitochondria within the cell.
Taken together, claims 1 and 19 of ‘724 teach a method of delivering a branched peptide composition to the mitochondria of a cell, wherein the peptide composition is the same as those of instant claim 1. Claims 5 and 15 teach an aqueous medium.
The difference between the claims of ‘724 and the instant claims is that ‘724 does not teach a viral vector or nucleic acid construct for delivery.
Gron teaches similar peptide compositions (e.g., SEQ ID NOs: 40-44, Table 1) as those of the instant claims for pharmaceutical compositions for expression and delivery to cells [0048, 0094]. This reference teaches a specific embodiment that comprises a recombinant vector containing a polynucleotide encoding a binding domain, including a peptide having binding specificity for bone for the recombinant production of the peptide [0114]. This reference teaches that the polynucleotide may be positioned in a prokaryotic expression vector so that when the peptide is produced in bacterial host cells (i.e., a transgene), it is expressed as a fusion protein with other amino acid sequences that assist in purification of the peptide or as recombinantly coupled to a surface-binding domain [0114].
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the peptides of ‘724, and used a recombinant viral vector for delivery into cells because Gron teaches similar peptides for the same delivery method into cells. One would be motivated to use a viral vector because Gron teaches that they can increase (i.e., facilitate) expression of the peptides in the mitochondria. As such, there is a reasonable expectation of success that the peptides of ‘724 can be delivered into cells with a viral vector, as these are standard in the art of protein expression in pharmaceutical formulations.
This meets the limitations of claims 82 by teaching the same branched peptides, recombinant viral vector in a method of delivery to the mitochondria by contacting a cell. Claims 87-91 are met because Gron further teaches that mammalian cell lines having introduced to (e.g., transfected or electroporated with) the viral expression vectors using viruses such as a vaccinia virus, adenovirus, adeno-associated virus, and retrovirus, and that successful expression of the peptide requires that either the recombinant nucleic acid molecule, including the encoding sequence of the peptide, or the vector itself, contain the necessary control elements for transcription and translation which is compatible with, and recognized by the particular host system used for expression [0115-0116]. Claim 17 of ‘724 teaches a micellular structure, meeting instant claim 89. Instant claims 94 and 95 are met because Gron teaches RNAi [0039] and that transgenes can be cloned in the vectors [0114-0117]. Instant claims 97-104 are met because the peptides of claims 1, 4-7 and 10-16 of ‘724 are drawn to all of the same instantly claimed peptides having the same branched sequences and side chains.
Response to Arguments/Remarks
Applicant's arguments filed 09/12/25 have been fully considered but they are not persuasive. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Applicants have submitted that because Gron does not teach branched peptides, there is no rational basis for combining the references.
Firstly, as discussed above in the teachings of Gron (para. 48 referenced; recited here in full, for purposes of rebuttal) “the peptide includes a binding domain having a contiguous sequence of no less than 7 amino acids and no more than about 50 amino acids in length, and multimers of the peptide; that is, linking more than one peptide to a branched polymeric linker using methods known in the art. A peptide for some embodiments, is produced by chemical synthesis, recombinant expression, biochemical or enzymatic fragmentation of a larger molecule, chemical cleavage of larger molecule, a combination of the foregoing or, in general, made by any other methods in the art, and, for some embodiments, isolated.”
Additionally, the peptides of Gron are similar in length and comprise both hydrophilic aromatic amino acids (See table 1). As such, the peptides are similar enough in structure to consider the Gron reference in combination with ‘724, especially in the context of the claimed method of delivery into the mitochondria, which is taught by both ‘724 (claim 19) and Gron [0114-0117].
As to the legal standard to combine, this requires that there be some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. Here, as discussed in the above rejection, ‘724 teaches the same peptides and a mitochondrial delivery method, but via a micelle. Gron teaches similar peptides used for the same mitochondrial delivery method of the instant claims, but with various types of vectors and nucleic acid constructs that can be used for delivering and expression, which have the same target as those delivered via micelles and can also be used in combination with micelles. As such, this meets the standard of the motivation to combine, with a reasonable expectation of success.
In further support of motivation to combine, what was generally known in the art at the filing date of the invention regarding recombinant viral vector delivery and nucleic acid constructs is also taken into consideration. Note that nucleic acid constructs is not defined in the specification, but it states (para. 0100) that expression constructs include any “nucleic acid constructs capable of directing expression of a gene or other nucleic acid sequence of interest and which can transfer such a nucleic acid sequence of interest to a target cell.”
Regarding what was generally available to one of ordinary skill in the art at the filing date of the invention, using viral vectors to delivery nucleic acids into cells for protein expression has been extensively covered in the in the prior art. In a review article by Ghosh et al. from 2020 (Cited here for purpose of rebuttal only), states that in the past three decades, viral vectors and nonviral gene delivery systems have been developed and have made recent encouraging advances (Viral Vector Systems for Gene Therapy: A comprehensive Review of Progress and Biosafety Challenges. Journal of ABSA International, 2020, Vol. 25(1) 7-18; Abstract). Ghosh teaches that as of 2019, almost 2600 gene therapy clinical trials have been completed or approved and about 70% of these trials use viral vectors (Introduction, p. 7, Col. 2). This reference also teaches viral vectors have generally proved efficient tools for gene delivery to target cells/tissue, a critical aspect of achieving therapeutic efficacy and that viral vector expression cassettes can be engineered with elements to enhance target specificity and transgene expression (spanning pp. 7-8). This reference provides a review of the 5 main classes of viral vectors that have been tested for clinical applications, which include retroviruses (RV), adenoviruses (AV), adeno associated viruses (AAV), lentiviruses (LV), and herpes simplex viruses (HSV), with a review of each and summary of references dating back to the early 2000s (Table 1, p. 9).
Additionally, specific to AAV protein delivery, Naso et al. provide a comprehensive review of this technology and its historical and widespread use in nucleic acid delivery from protein expression (Adeno Associated Virus (AAV) as a Vector for Gene Therapy. BioDrugs, 2017, Jul 131(4): 317-334). Specific to mitochondrial delivery with vectors and nucleic acid constructs Jang and Lim provide a review article from 2018 outlining mitochondrial delivery methods (Recent Advances in Mitochondria-Targeted Gene Delivery, Molecules. 2018, Vol. 23, 2316; p. 1-16). Both references are cited here only for purposes of rebuttal to show what was generally known in the art.
As such, the standard for obviousness is met by the teachings of Gron, not only because of its specific content in the above rejection, but also because the standard for obviousness is also based on knowledge which is generally available to one of ordinary skill in the art. Here, as these evidentiary references demonstrate, knowledge of vector and nucleic acid delivery systems for peptides was generally well-known and available to one of ordinary skill in the art well before the effective filing date of the invention.
Therefore, the rejection is upheld.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654