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 without traverse of Group I in the reply filed on April 21st, 2026 is acknowledged.
Applicant’s election without traverse of (1) KRIWQRIK (all D-amino acids); (2) SEQ ID NO: 4; (3) 10 carbons; (4) the fatty acid is saturated and; (5) amide bond in the reply filed on April 21st, 2026 is acknowledged.
In the interest of compact prosecution, the examination and search were extended to the non-elected species (1) KRIWQRIKDF (SEQ ID NO:3) and KRIVQRIKDF (SEQ ID NO: 12) and (4) octanoic acid as the prior art pertaining to the elected species applies. Therefore, claims 6 and 15, reading on the above stated species were not withdrawn.
Claims 19-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 April 21st, 2026.
Priority
The instant application claims priority to 371 National Stage Application PCT/US22/25930, filed April 22nd, 2022, under 35 U.S.C. 119(a)-(d), and claims benefit to provisional application 63178637, filed April 23rd, 2021, under 35 U.S.C.119 (e). The priority date of April 23rd, 2021 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 26th, 2024 is being considered by the examiner.
Claims Status
The claims listing filed on August 25th. 2023 is pending. Claims 19-24 are withdrawn from further consideration for the reasons set forth in the restriction requirement, 37 CFR 1.142(b). Claims 1-18 are being examined on the merits in this office action. Claims 1-18 are rejected.
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 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 7465784 in view of EP3434287B1 (published Jan 27th, 2021).
7465784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX [claim 1]. The LL-37 peptide comprises instant SEQ ID NO:8, where instant X is V.
7465784 does not outrightly specify that the peptide is lipidated by a fatty acid and that this is done at the N-terminus.
In the specifications, 7465784 further states that the peptide
“may have capping, protecting and/or stabilizing moieties at the C-terminus and/or N-terminus. Such moieties are well known in the art and include, without limitation, amidation and acetylation. The peptide template may also be lipidated or glycosylated at any amino acid” [pg 22 Col 10 line 45]. 7465784 is available prior art and it is permissible to use available prior art in an obviousness-type non-statutory double patenting rejection.
3434287 claims a lipopeptide having a FA-A-B-A'-NH2, wherein FA represents a fatty acid selected from caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic), pentadecanoic acid and palmitic acid (hexadecanoic); unit A and A' independently consist of 1, 2 or 3 amino acids selected from the group of basic amino acids or hydrophobic amino acids; unit B consist of 1, 2 or 3 amino acids, selected from the group (a) of hydrophobic amino acids and (b) the group of hydrogen-bond forming amino acids [claim 1]. 3434287 teaches that short lipidated peptides provide enhanced anti-microbial and anti-fungal activity over the inactive or weakly inactive base tetrapeptide or hexapeptides [0001].
Therefore, it would have been obvious for the applicant to make a lipopeptide comprising a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 2, 7465784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all 12 amino acids of instant SEQ ID NO:8, where instant X is V [claim 1]. Therefore, it would have been obvious for the applicant to make an antimicrobial lipopeptide comprising of the 4, 5, 6, 7, 8, 9, 10, or 11 N-terminal amino acids of instant SEQ ID NO: 8, and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 3, 7465784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all four amino acids of instant SEQ ID NO: 9. Therefore, it would have been obvious for the applicant to make an antimicrobial lipopeptide comprising KRIV (SEQ ID NO: 9) and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 4, 7465784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all six amino acids of instant SEQ ID NO: 10. Therefore, it would have been obvious for the applicant to make an antimicrobial lipopeptide comprising KRIVQR (SEQ ID NO: 10) and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 5, 7465784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all eight amino acids of instant SEQ ID NO: 11. Therefore, it would have been obvious for the applicant to make an antimicrobial peptide comprising KRIVQRIK (SEQ ID NO: 11) and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 6, 7465784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all 10 amino acids of instant SEQ ID NO: 12. Therefore, it would have been obvious for the applicant to take an antimicrobial lipopeptide comprising KRIVQRIKDF (SEQ ID NO: 12) and adding a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 7, the formula FA-A-B-A'-NH2, taught by 3434287, selects FA from caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic), pentadecanoic acid and palmitic acid (hexadecenoic), all of which are saturated fatty acids [claim 1]. Therefore, it would have been obvious for the applicant to make a lipopeptide with a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a saturated fatty acid, wherein said saturated fatty acid is conjugated to the N-terminus of the peptide for the best expectation of success at enhancing its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 8, of the fatty acids taught by 3434287, caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic) are C6, C8, C10, and C14 fatty acids, respectively. Therefore, it would have been obvious for the applicant to make a lipopeptide with a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a C6-C14 fatty acid, wherein said C6-C14 fatty acid is conjugated to the N-terminus of the peptide for the best expectation of success at enhancing its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 9, of the fatty acids taught by 3434287, caprylic acid (octanoic) and capric acid (decanoic) are C8 and C10 fatty acids, respectively. Therefore, it would have been obvious for the applicant to make a lipopeptide with a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a C7-C11 fatty acid, wherein said C7-C11 fatty acid is conjugated to the N-terminus of the peptide for the best expectation of success at enhancing its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 10, of the fatty acids taught by 3434287, caprylic acid (octanoic) and capric acid (decanoic) are C8 and C10 fatty acids, respectively. Therefore, it would have been obvious for the applicant to make a lipopeptide with a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a saturated fatty acid, wherein said saturated fatty acid is conjugated to the N-terminus of the peptide for the best expectation of success at enhancing its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 11, 7465784 goes on to claim the isolated LL-37 peptide where at least one amino acid at position 4, 8, and 12 is a D-amino acid [claim 1]. Therefore, it would have been obvious for the applicant to make a lipopeptide comprising a peptide which is a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V and at least one amino acid is a D-amino acid; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 12, 7465784 goes on to claim the isolated LL-37 peptide comprising D-amino acids spaced by three consecutive L-amino acids [claim 7]. The sequence of the LL-37 peptide is FKRIVQRIKDFLRX1, wherein X1 is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, and 8 amino acids [claim 1]. The broadest reasonable interpretation encompasses instant SEQ ID NO:8 being all D-amino acids, and all of the other amino acids of the isolated LL-37 peptide being L-amino acids (FKRIVQRIKDFLRX1). Therefore, it would have been obvious for the applicant to make a lipopeptide comprising a peptide which is a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8) with D-amino acids, wherein X is W or V; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 13, 3434287 claims a lipopeptide having a FA-A-B-A'-NH2, where the C-terminus is amidated. Therefore, it would have been obvious for the applicant to make lipopeptide comprising a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V and the C-terminus is amidated; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide bond, as taught by 3434287, because doing so would make it more successful at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 14, the fatty acid of formula FA-A-B-A'-NH2, taught by 3434287, is conjugated to the N-terminus [claim 1 and [0125]]. An artisan of ordinary skill knows that when an amine and carboxylic acid (the reactive group of the fatty acid) react, they form an amide bond. Therefore, it would have been obvious for the applicant to take lipopeptide comprising a peptide which is a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide through an amide bond, as taught by 3434287, because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 15, 7465784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all 10 amino acids of instant SEQ ID NO: 12. Of the fatty acids taught by 3434287, caprylic acid (octanoic) is a C8 fatty acid. Therefore, it would have been obvious for the applicant to make a antimicrobial lipopeptide, comprising KRIVQRIKDF (SEQ ID NO: 12) and octanoic acid, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 16, 7465784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all eight amino acids of instant SEQ ID NO: 11. Of the fatty acids taught by 3434287, capric acid (decanoic) is a C10 fatty acid. Therefore, it would have been obvious for the applicant to make a antimicrobial lipopeptide, comprising KRIVQRIK (SEQ ID NO: 11) and decanoic acid, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 17, 7465784 goes on to claim at least one LL-37 peptide and at least one pharmaceutically acceptable carrier [claim 8]. Therefore, it would have been obvious for the applicant to make a lipopeptide comprising a peptide which is a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide through an amide bond with a pharmaceutically acceptable carrier, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 18, 7465784 specifies that the “pharmaceutical compositions of the instant invention may also comprise at least one other anti-microbial agent (e.g., anti-bacterial agents such as antibiotics)” [Pg 23 Col 12 Line 32]. Therefore, it would have been obvious for the applicant to make an antimicrobial lipopeptide comprising peptide KRIVQRIK (SEQ ID NO: 11) and decanoic acid with an antibiotic, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Claims 1-18 are also rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-7, and 9-10 of U.S. Patent No. 10144767 in view of EP3434287B1 (published Jan 27th, 2021).
10144767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W (SEQ ID NO: 17), wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claim 1 and 3]. A generic disclosure will anticipate a claimed species covered by that disclosure when the species can be “at once envisaged” from the disclosure [see MPEP § 2131.02]. In the present case, the number of amino acids selected for variables X1–X3 is sufficiently limited that one of ordinary skill in the art can readily envisage the species within the claimed genus.
Furthermore, 10144767’s claimed SEQ ID NO:2 comprises of the truncate KRIW of instant SEQ ID NO:8, where X is W [claim 4]. 10144767 goes on to specify that the peptide “may have capping, protecting and/or stabilizing moieties at the C-terminus and/or N-terminus. Such moieties are well known in the art and include, without limitation, amidation and acetylation. The peptide template may also be lipidated or glycosylated at any amino acid” [pg 24 Col 6 line 35]. 10144767 is available prior art and it is permissible to use available prior art in an obviousness-type non-statutory double patenting rejection. 10144767 does not outrightly specify that the peptide is lipidated by a fatty acid and that this is done at the N-terminus.
3434287 claims a lipopeptide having a FA-A-B-A'-NH2, wherein FA represents a fatty acid selected from caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic), pentadecanoic acid and palmitic acid (hexadecanoic); unit A and A' independently consist of 1, 2 or 3 amino acids selected from the group of basic amino acids or hydrophobic amino acids; unit B consist of 1, 2 or 3 amino acids, selected from the group (a) of hydrophobic amino acids and (b) the group of hydrogen-bond forming amino acids [claim 1]. 3434287 teaches that short lipidated peptides provide enhanced anti-microbial and anti-fungal activity over the inactive or weakly inactive base tetrapeptide or hexapeptides [0001].
Therefore, it would have been obvious for the applicant to make a lipopeptide comprising a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 2, 10144767’s claimed SEQ ID NO:2 comprises of truncate KRIW of instant SEQ ID NO:8, the first four N-terminal amino acids, where X is W [claim 4]. Therefore, it would have been obvious for the applicant to make an antimicrobial lipopeptide comprising of the 4, 5, 6, 7, 8, 9, 10, or 11 N-terminal amino acids of instant SEQ ID NO: 8, and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 3, 10144767’s claimed SEQ ID NO:2 comprises of instant SEQ ID NO: 6. Therefore, it would have been obvious for the applicant to make an antimicrobial lipopeptide comprising KRIW (SEQ ID NO: 6) and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 4, 10144767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claim 1 and 3]. 10144767’s claimed SEQ ID NO: 2 comprises terminally of the truncate KRIW of instant SEQ ID NO: 5 [claim 4]. 10144767’s does not specifically claim the sequence including the latter two residues Q and R.
10144767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae. The peptide coated surface also demonstrates anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 4-mer truncate are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging 10144767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQR because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Therefore, it would have been obvious for the applicant to take 10144767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a fatty acid on the N-terminus, to make an antimicrobial lipopeptide comprising KRIWQR (SEQ ID NO: 5) and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 5, 10144767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claim 1 and 3]. 10144767’s claimed SEQ ID NO: 2 comprises terminally of the truncate KRIW of instant SEQ ID NO: 4 [claim 4]. 10144767’s does not specifically claim the sequence including the latter four residues Q, R, I, and K.
10144767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae. The peptide coated surface also demonstrates anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 4-mer truncate are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging 10144767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQRIK because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Therefore, it would have been obvious for the applicant to take 10144767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a fatty acid on the N-terminus to make an antimicrobial lipopeptide comprising KRIWQRIK (SEQ ID NO: 4) and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 6, 10144767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claim 1 and 3]. 10144767’s claimed SEQ ID NO: 2 comprises terminally of the truncate KRIW of instant SEQ ID NO: 4 [claim 4]. 10144767’s does not specifically claim the sequence including the latter six residues Q, R, I K, D, and F.
10144767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae. The peptide coated surface also demonstrates anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 4-mer truncate are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging 10144767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQRIKKDF because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Therefore, it would have been obvious for the applicant to take 10144767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a fatty acid on the N-terminus, to make an antimicrobial lipopeptide comprising KRIWQRIKDF (SEQ ID NO: 6) and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 7, the formula FA-A-B-A'-NH2, taught by 3434287, selects FA from caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic), pentadecanoic acid and palmitic acid (hexadecenoic), all of which are saturated fatty acids [claim 1]. Therefore, it would have been obvious for the applicant to make a lipopeptide with a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a saturated fatty acid, wherein said saturated fatty acid is conjugated to the N-terminus of the peptide for the best expectation of success at enhancing its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 8, of the fatty acids taught by 3434287, caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic) are C6, C8, C10, and C14 fatty acids, respectively. Therefore, it would have been obvious for the applicant to make a lipopeptide with a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a C6-C14 fatty acid, wherein said C6-C14 fatty acid is conjugated to the N-terminus of the peptide for the best expectation of success at enhancing its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 9, of the fatty acids taught by 3434287, caprylic acid (octanoic) and capric acid (decanoic) are C8 and C10 fatty acids, respectively. Therefore, it would have been obvious for the applicant to make a lipopeptide with a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a C7-C11 fatty acid, wherein said C7-C11 fatty acid is conjugated to the N-terminus of the peptide for the best expectation of success at enhancing its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 10, of the fatty acids taught by 3434287, caprylic acid (octanoic) and capric acid (decanoic) are C8 and C10 fatty acids, respectively. Therefore, it would have been obvious for the applicant to make a lipopeptide with a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a saturated fatty acid, wherein said saturated fatty acid is conjugated to the N-terminus of the peptide for the best expectation of success at enhancing its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 11, 10144767 goes on to claim an isolated peptide comprising the amino acid sequence WWWLX1X2X3W wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from the group consisting of Ile, Arg, and Lys, wherein said peptide comprises at least one D-amino acid [claims 1 and 5]. Therefore, it would have been obvious for the applicant to make a lipopeptide comprising a peptide which is a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V and at least one amino acid is a D-amino acid; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 12, 10144767 goes on to claim an isolated peptide comprising the amino acid sequence WWWLX1X2X3W wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from the group consisting of Ile, Arg, and Lys, wherein all of the amino acids are D-amino acids [claims 1 and 7]. Therefore, it would have been obvious for the applicant to make a lipopeptide comprising a peptide which is a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8) with D-amino acids, wherein X is W or V; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 13, 10144767 goes on to claim the peptide comprising at least one modification selected from the group consisting of amidation and acetylation [claim 7]. Therefore, it would have been obvious for the applicant to make lipopeptide comprising a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V and has an amidation; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide bond, as taught by 3434287, because doing so would make it more successful at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 14, the fatty acid of formula FA-A-B-A'-NH2, taught by 3434287, is conjugated to the N-terminus [claim 1 and [0125]]. An artisan of ordinary skill knows that when an amine and carboxylic acid (the reactive group of the fatty acid) react, they form an amide bond. Therefore, it would have been obvious for the applicant to take lipopeptide comprising a peptide which is a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide through an amide bond, as taught by 3434287, because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 15, 10144767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claim 1 and 3]. 10144767’s claimed SEQ ID NO: 2 comprises terminally of the truncate KRIW of instant SEQ ID NO: 4 [claim 4]. 10144767’s does not specifically claim the sequence including the latter six residues Q, R, I K, D, and F.
10144767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae. The peptide coated surface also demonstrates anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 4-mer truncate are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging 10144767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQRIKKDF because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Of the fatty acids taught by 3434287, caprylic acid (octanoic) is a C8 fatty acid. Therefore, it would have been obvious for the applicant to take 10144767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a octanoic acid on the N-terminus, to make a antimicrobial lipopeptide comprising KRIVQRIKDF (SEQ ID NO: 12) and octanoic acid, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 16, 10144767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claim 1 and 3]. 10144767’s claimed SEQ ID NO: 2 comprises terminally of the truncate KRIW of instant SEQ ID NO: 4 [claim 4]. 10144767’s does not specifically claim the sequence including the latter four residues Q, R, I, and K.
10144767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae. The peptide coated surface also demonstrates anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 4-mer truncate are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging 10144767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQRIK because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Of the fatty acids taught by 3434287, capric acid (decanoic) is a C10 fatty acid. Therefore, it would have been obvious for the applicant to take 10144767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a decanoic acid on the N-terminus, to make a antimicrobial lipopeptide, comprising KRIVQRIK (SEQ ID NO: 11) and decanoic acid, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 17, 10144767 goes on to the peptide with at least one pharmaceutically acceptable carrier [claim 9]. Therefore, it would have been obvious for the applicant to make a lipopeptide comprising a peptide which is a truncation of the amino acid sequence KRIXQRIKDFLR (SEQ ID NO: 8), wherein X is W or V; and a fatty acid, wherein said fatty acid is conjugated to the N-terminus of the peptide through an amide bond with a pharmaceutically acceptable carrier, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Regarding claim 18, 10144767 goes on to claim the peptide with at least one pharmaceutically acceptable carrier and at least one antibiotic [claims 1, and 9-10]. Therefore, it would have been obvious for the applicant to make an antimicrobial lipopeptide comprising peptide KRIWQRIK (SEQ ID NO: 4) and decanoic acid with an antibiotic, because doing so would enhance its anti-microbial and anti-fungal activity, as taught by 3434287.
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-18 are rejected under 35 U.S.C. 103 as being obvious over ‘784 (US7465784B2; Published 2008) in view of Romani et al. (EP3434287B1; Published 2021).
In the reply filed on April 21st, 2026, 1) KRIWQRIK (all D-amino acids); (2) SEQ ID NO: 4; (3) 10 carbons; (4) the fatty acid is saturated and; (5) amide bond. The same prior art applying to the elected species applies to the remaining claims of Group I, so all its claims were examined on the merits.
‘784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX [claim 1]. The LL-37 peptide comprises instant SEQ ID NO:8, where instant X is V. In the specifications, ‘784 further states that the peptide
“may have capping, protecting and/or stabilizing moieties at the C-terminus and/or N-terminus. Such moieties are well known in the art and include, without limitation, amidation and acetylation. The peptide template may also be lipidated or glycosylated at any amino acid” [pg 22 Col 10 line 45].
‘784 does not outrightly specify that the peptide is lipidated by a fatty acid and this is done at the N-terminus.
Romani et al. claims a lipopeptide having a FA-A-B-A'-NH2 template, wherein FA represents a fatty acid selected from:
caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic), pentadecanoic acid and palmitic acid (hexadecanoic); unit A and A' independently consist of 1-3 basic or hydrophobic amino acids; unit B consist of 1-3 hydrophobic or hydrogen-bond forming amino acids, [claim 1]. Romani et al. also teaches that short lipidated peptides provide enhanced anti-microbial and anti-fungal activity over the inactive or weakly inactive base tetrapeptide or hexapeptides [0001].
Therefore, it would have been obvious for the applicant to take instant SEQ ID NO: 8 and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 2, ‘784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all 12 amino acids of instant SEQ ID NO:8, where instant X is V [claim 1]. Therefore, it would have been obvious for the applicant to take a sequence with all 12 N-terminal amino acids of instant SEQ ID NO: 8 and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 3, ‘784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all four amino acids of instant SEQ ID NO: 9. Therefore, it would have been obvious for the applicant to take a sequence comprising instant SEQ ID NO: 9 and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 4, ‘784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all six amino acids of instant SEQ ID NO: 10. Therefore, it would have been obvious for the applicant to take a sequence comprising instant SEQ ID NO: 10 and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 5, ‘784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all eight amino acids of instant SEQ ID NO: 11. Therefore, it would have been obvious for the applicant to take a sequence comprising instant SEQ ID NO: 11 and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 6, ‘784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all 10 amino acids of instant SEQ ID NO: 12. Therefore, it would have been obvious for the applicant to take a sequence comprising instant SEQ ID NO: 12 and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 7, the formula FA-A-B-A'-NH2, taught by Romani et al., selects FA from caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic), pentadecanoic acid and palmitic acid (hexadecenoic), all of which are saturated fatty acids [claim 1]. Therefore, it would have been obvious for the applicant to take instant SEQ ID NO:8 and lipidate it with the saturated fatty acids taught by Romani et al. on the N-terminus for the best expectation of success at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 8, of the fatty acids taught by Romani et al., caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic) are C6, C8, C10, and C14 fatty acids, respectively. Therefore, it would have been obvious for the applicant to take instant SEQ ID NO:8 and lipidate it with the C6-C14 fatty acids taught by Romani et al. on the N-terminus for the best expectation of success at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 9, of the fatty acids taught by Romani et al., caprylic acid (octanoic) and capric acid (decanoic) are C8 and C10 fatty acids, respectively. Therefore, it would have been obvious for the applicant to take instant SEQ ID NO:8 and lipidate it with the C7-C11 fatty acids taught by Romani et al. on the N-terminus for the best expectation of success at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 10, of the fatty acids taught by Romani et al., caprylic acid (octanoic) and capric acid (decanoic) are C8 and C10 fatty acids, respectively. Therefore, it would have been obvious for the applicant to take instant SEQ ID NO:8 and lipidate it with the C8-C10 fatty acids taught by Romani et al. on the N-terminus for the best expectation of success at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 11, ‘784 goes on to claim the isolated LL-37 peptide where at least one amino acid at position 4, 8, and 12 is a D-amino acid [claim 1]. Therefore, it would have been obvious for the applicant to take instant SEQ ID NO:8 with at least one D-amino acid and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 12, ‘784 goes on to claim the isolated LL-37 peptide comprising D-amino acids spaced by three consecutive L-amino acids [claim 7]. The sequence of the LL-37 peptide is FKRIVQRIKDFLRX1, wherein X1 is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, and 8 amino acids [claim 1]. The broadest reasonable interpretation encompasses instant SEQ ID NO: 8 being all D-amino acids, and all of the other amino acids of the isolated LL-37 peptide being L-amino acids (FKRIVQRIKDFLRX1) when X--1 is two or more amino acids in length. Therefore, it would have been obvious for the applicant to take a composition comprising instant SEQ ID NO: 8 with all D-amino acids and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 13, Romani et al. claims a lipopeptide having a FA-A-B-A'-NH2, where the C-terminus is amidated. Therefore, it would have been obvious for the applicant to take instant SEQ ID NO: 8, amidate the C-terminus, and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would make it more successful at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 14, the fatty acid of formula FA-A-B-A'-NH2, taught by Romani et al., is conjugated to the N-terminus [claim 1 and [0125]]. An artisan of ordinary skill knows that when an amine and carboxylic acid (the reactive group of the fatty acid) react, they form an amide bond. Therefore, it would have been obvious for the applicant to take instant SEQ ID NO: 8 and lipidate it with a fatty acid conjugated by an amide bond, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 15, ‘784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all 10 amino acids of instant SEQ ID NO: 12. Of the fatty acids taught by Romani et al., caprylic acid (octanoic) is a C8 fatty acid. Therefore, it would have been obvious for the applicant to take a sequence comprising instant SEQ ID NO: 12 and lipidate it with an octanoic acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 16, ‘784 claims an isolated LL-37 peptide having the amino acid sequence FKRIVQRIKDFLRX, comprising all eight amino acids of instant SEQ ID NO: 11. Of the fatty acids taught by Romani et al., capric acid (decanoic) is a C10 fatty acid. Therefore, it would have been obvious for the applicant to take a sequence comprising instant SEQ ID NO: 12 and lipidate it with a decanoic acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 17, ‘784 goes on to claim at least one LL-37 peptide and at least one pharmaceutically acceptable carrier [claim 8]. Therefore, it would have been obvious for the applicant to take the LL-37 peptide comprising instant SEQ ID NO:8 and a pharmaceutically acceptable carrier and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 18, ‘784 specifies that the “pharmaceutical compositions of the instant invention may also comprise at least one other anti-microbial agent (e.g., anti-bacterial agents such as antibiotics)” [Pg 23 Col 12 Line 32]. Therefore, it would have been obvious for the applicant to take a pharmaceutical composition comprising instant SEQ ID NO: 12, lipidate it with a decanoic acid on the N-terminus, as taught by Romani et al., and add an antibiotic because doing so would enhance its anti-microbial and anti-fungal activity.
Claims 1-18 are also rejected under 35 U.S.C. 103 as being obvious over ‘767 (US10144767B2; Published 2018) in view of Romani et al. (EP3434287B1; Published 2021).
In the reply filed on April 21st, 2026, 1) KRIWQRIK (all D-amino acids); (2) SEQ ID NO: 4; (3) 10 carbons; (4) the fatty acid is saturated and; (5) amide bond. The same prior art applying to the elected species applies to the remaining claims of Group I, so all its claims were examined on the merits.
‘767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W (SEQ ID NO: 17), wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claims 1 and 3]. A generic disclosure will anticipate a claimed species covered by that disclosure when the species can be “at once envisaged” from the disclosure [see MPEP § 2131.02]. In the present case, the number of amino acids selected for variables X1–X3 is sufficiently limited that one of ordinary skill in the art can readily envisage the species within the claimed genus. Furthermore, ‘767’s claimed SEQ ID NO:2 comprises of the truncate KRIW of instant SEQ ID NO:8, where X is W [claim 4]. ‘767 further states that the peptide
“may have capping, protecting and/or stabilizing moieties at the C-terminus and/or N-terminus. Such moieties are well known in the art and include, without limitation, amidation and acetylation. The peptide template may also be lipidated or glycosylated at any amino acid” [pg 24 Col 6 line 35].
‘767 does not outrightly specify that the peptide is lipidated by a fatty acid and that this is done at the N-terminus.
Romani et al. claims a lipopeptide having a FA-A-B-A'-NH2, wherein FA represents a fatty acid selected from:
caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic), pentadecanoic acid and palmitic acid (hexadecanoic); unit A and A' independently consist of 1-3 basic or hydrophobic amino acids and; unit B consist of 1-3 hydrophobic or hydrogen-bond forming amino acids [claim 1]. Romani et al. also teaches that short lipidated peptides provide enhanced anti-microbial and anti-fungal activity over the inactive or weakly inactive base tetrapeptide or hexapeptides [0001].
Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO: 8 and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 2, ‘767’s claimed SEQ ID NO: 2 comprises of truncate KRIW of instant SEQ ID NO:8, the first four N-terminal amino acids, where X is W [claim 4]. Therefore, it would have been obvious for the applicant to take a truncate comprising the first four N-terminal amino acids of instant SEQ ID NO:8 and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 3, ‘767’s claimed SEQ ID NO:2 comprises of instant SEQ ID NO: 6. Therefore, it would have been obvious for the applicant to take a composition comprising of instant SEQ ID NO: 6 and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 4, ‘767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claims 1 and 3]. ‘767’s claimed SEQ ID NO: 2 comprises terminally of the truncate KRIW of instant SEQ ID NO: 5’s KRIWQR [claim 4]. ‘767’s does not specifically claim the sequence including the latter two residues Q and R.
‘767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae and anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 4-mer truncate (KRIW) are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging ‘767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQR because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Therefore, it would have been obvious for the applicant to take ‘767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., to enhance its anti-microbial and anti-fungal activity.
Regarding claim 5, ‘767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claims 1 and 3]. ‘767’s claimed SEQ ID NO: 2 comprises terminally of the truncate KRIW of instant SEQ ID NO: 4 (KRIWQRIK) [claim 4]. ‘767’s does not specifically claim the sequence including the latter four residues Q, R, I, and K.
‘767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae and anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 6-mer truncate (KRIWQRIK) are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging ‘767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQRIK because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Therefore, it would have been obvious for the applicant to take ‘767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., to enhance its anti-microbial and anti-fungal activity.
Regarding claim 6, ‘767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claims 1 and 3]. ‘767’s claimed SEQ ID NO: 2 comprises terminally of the truncate KRIW of instant SEQ ID NO: 3 (KRIWQRIKDF) [claim 4]. ‘767’s does not specifically claim the sequence including the latter six residues Q, R, I, K, D, and F.
‘767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae and anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 8-mer truncate (KRIWQRIKDF) are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging ‘767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQRIKKDF because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Therefore, it would have been obvious for the applicant to take ‘767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., to enhance its anti-microbial and anti-fungal activity.
Regarding claim 7, the formula FA-A-B-A'-NH2, taught by Romani et al., selects FA from caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic), pentadecanoic acid and palmitic acid (hexadecenoic), all of which are saturated fatty acids [claim 1]. Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO:8, like ‘767’s claimed SEQ ID NO:2 , and lipidate it with the saturated fatty acids taught by Romani et al. on the N-terminus for the best expectation of success at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 8, of the fatty acids taught by Romani et al., caproic acid (hexanoic), caprylic acid (octanoic), capric acid (decanoic), lauric acid (dodecanoic), mystiric acid (tetradecanoic) are C6, C8, C10, and C14 fatty acids, respectively. Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO: 8, like ‘767’s claimed SEQ ID NO:2, and lipidate it with the C6-C14 fatty acids taught by Romani et al. on the N-terminus for the best expectation of success at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 9, of the fatty acids taught by Romani et al., caprylic acid (octanoic) and capric acid (decanoic) are C8 and C10 fatty acids, respectively. Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO: 8, like ‘767’s claimed SEQ ID NO: 2, and lipidate it with the C7-C11 fatty acids taught by Romani et al. on the N-terminus for the best expectation of success at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 10, of the fatty acids taught by Romani et al., caprylic acid (octanoic) and capric acid (decanoic) are C8 and C10 fatty acids, respectively. Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO:8, like ‘767’s claimed SEQ ID NO:2, and lipidate it with the C8-C10 fatty acids taught by Romani et al. on the N-terminus for the best expectation of success at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 11, ‘767 goes on to claim an isolated peptide comprising the amino acid sequence WWWLX1X2X3W wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from the group consisting of Ile, Arg, and Lys, wherein said peptide comprises at least one D-amino acid [claims 1 and 5]. Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO:8, like ‘767’s claimed SEQ ID NO:2, with at least one D-amino acid and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 12, ‘767 goes on to claim an isolated peptide comprising the amino acid sequence WWWLX1X2X3W wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from the group consisting of Ile, Arg, and Lys, wherein all of the amino acids are D-amino acids [claims 1 and 7]. Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO:8, like ‘767’s claimed SEQ ID NO:2, with all D-amino acids and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 13, ‘767 goes on to claim the peptide comprising at least one modification selected from the group consisting of amidation and acetylation [claim 7].. Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO:8, like ‘767’s claimed SEQ ID NO:2, amidate the C-terminus, and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would make it more successful at enhancing its anti-microbial and anti-fungal activity.
Regarding claim 14, the fatty acid of formula FA-A-B-A'-NH2, taught by Romani et al., is conjugated to the N-terminus [claim 1 and [0125]]. An artisan of ordinary skill knows that when an amine and carboxylic acid (the reactive group of the fatty acid) react, they form an amide bond. Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO:8, like ‘767’s claimed SEQ ID NO:2, and lipidate it with a fatty acid conjugated by an amide bond, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 15, ‘767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claims 1 and 3]. ‘767’s claimed SEQ ID NO: 2 comprises terminally of the truncate (KRIWQRIKDF) of instant SEQ ID NO: 3 [claim 4]. ‘767’s does not specifically claim the sequence including the latter six residues Q, R, I K, D, and F.
‘767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae and anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 8-mer truncate (KRIWQRIKDF) are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging ‘767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQRIKDF because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Of the fatty acids taught by Romani et al., caprylic acid (octanoic) is a C8 fatty acid. Therefore, it would have been obvious for the applicant to take ‘767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a octanoic acid on the N-terminus, as taught by Romani et al., to enhance its anti-microbial and anti-fungal activity.
Regarding claim 16, ‘767 claims an isolated peptide comprising the amino acid sequence WWWLX1X2X3W, wherein X1 and X2 are independently Arg or Lys, and wherein X3 is selected from a group consisting of Ile, Arg, and Lys [claims 1 and 3]. ‘767’s claimed SEQ ID NO: 2 comprises terminally of the truncate KRIW of instant SEQ ID NO: 4 (KRIWQRIK) [claim 4]. ‘767’s does not specifically claim the sequence including the latter four residues Q, R, I, and K.
‘767 discloses that sequence FKRIVQRIKDFLRNLV, the most potent LL-37 peptide, shows activity against a panel of the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa and Enterobacter cloacae and anti-biofilm activity against methicillin-resistant S. aureus (MRSA) and E. coli [Pg 37 Col 31 line 37-46]. The first three amino acids of the 6-mer truncate are present in the potent LL-37 peptide. It would have been routine optimization to the applicant to make a peptide comprising claimed SEQ ID NO:2 by merging ‘767’s claimed SEQ ID NO:2 with the amino acids following the KRI motif from the potent LL-37 peptide FKRIVQRIKDFLRNLV to make a peptide comprising the truncate KRIWQRIK because the LL-37 peptide shows broad-spectrum activity, suggesting that a peptide comprising SEQ ID NO:2 comprising the LL-37 peptide with a W instead of V would have a reasonable expectation of showing the same efficacy.
Of the fatty acids taught by Romani et al., capric acid (decanoic) is a C10 fatty acid. Therefore, it would have been obvious for the applicant to take ‘767’s claimed SEQ ID NO:2, optimize it using the LL-37 peptide’s sequence, and lipidate it with a decanoic acid on the N-terminus, as taught by Romani et al., to enhance its anti-microbial and anti-fungal activity.
Regarding claim 17, ‘767 goes on to the peptide with at least one pharmaceutically acceptable carrier [claim 9]. Therefore, it would have been obvious for the applicant to take a truncate of instant SEQ ID NO:8, like ‘767’s claimed SEQ ID NO:2, and a pharmaceutically acceptable carrier and lipidate it with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Regarding claim 18, ‘767, goes on to claim the peptide with at least one pharmaceutically acceptable carrier and at least one antibiotic [claims 1, and 9-10]. Therefore, it would have been obvious for the applicant to take instant SEQ ID NO:4, a pharmaceutically acceptable carrier, and an antibiotic and lipidate the peptide with a fatty acid on the N-terminus, as taught by Romani et al., because doing so would enhance its anti-microbial and anti-fungal activity.
Summary
Claims 1-18 are rejected on the ground of nonstatutory double patenting. Claims 1-18 are rejected under 35 U.S.C. 103.
Correspondence
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/SACHI JAUHARI/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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