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 .
Status of the Claims
Claims 2, 4, and 6 are cancelled.
Claims 1, 3, 5, and 7-20 are pending.
Claims 1, 3, 5, and 7-20 are examined herein.
The previous rejection under 35 USC 101 has been withdrawn in view of Applicant’s amendments to the claim(s).
The previous rejection under 35 USC 102 has been withdrawn in view of Applicant’s amendments to the claim(s). However, in view of Applicant’s amendments the claims are nor rejected under 35 USC 103.
Claims 1, 3, 5, and 7-20 are rejected.
Priority
Application No. 18/644,446 filed on 04/24/2024 claims priority to provisional Application No. 63/497,753 filed on 04/24/2023.
Election/Restrictions
As stated in the prior Office Action, Applicant’s election of species of SEQ ID NOs: 33, 14, 27, and 28 in the reply filed on 10/23/2025 is acknowledged.
Priority
As stated in the previous Office Action, Application No. 18/644,446 filed on 04/24/2024 claims priority to provisional Application No. 63/497,753 filed on 04/24/2023.
Election/Restrictions
As stated in the previous Office Action, Applicant’s election of species of SEQ ID NOs: 33, 14, 27, and 28 in the reply filed on 10/23/2025 is acknowledged.
Claim Rejections - 35 USC § 112
Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 5, 8, and 9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a maintained rejection from the Office Action dated 11/18/2025.
Claims 1, 5, 8, and 9, are broadly drawn to any homolog of the recited SEQ ID NOs.
Applicant describes in certain embodiments, a homolog of an amino acid sequence can comprise an amino acid sequence that varies from a reference amino acid sequence by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues. For example, the protein binding sequence BamA_00901 (MGLLGLCDLIFYVYNVYWVE (SEQ ID NO: 10)) varies by a single amino acid when compared to protein binding sequence BamA_00902 (MGLLGLCDLIFYGYNVYWVE (SEQ ID NO: 11)). Additionally, the protein binding sequence of peptide 9 (FGGSVGGSH (SEQ ID NO: 16)) varies by three amino acid residues compared to peptide 10 (FGSGVGSGH (SEQ ID NO: 17)) (specification, p. 16).
Applicant has not described the required structures in any antimicrobial peptide sequence or any homolog thereof necessary for the sequences to maintain the function of an antimicrobial and/or protein binding peptide.
The prior art fails to remedy this deficiency. Elected SEQ ID NOs: 27 and 27 are comprised of the elected binding peptide SEQ ID NO: 14 and elected antimicrobial peptide SEQ ID NO: 33. Regarding elected SEQ ID NO: 14, there appears to be a dearth of description of homolog amino acid sequences that would be expected to have the peptide binding function. For example, there is an identity gap exhibited below in sequential search results of SEQ ID NO: 28 (which is a sequence from the instant application comprising seq id no: 14), and the next most similar sequence showing about 50% identity to a sequence of an unrelated invention of nucleic acid and amino acid sequences relating to moraxella catarrhalis:
RESULT 5
US-18-644-446-28
Sequence 28, US/18644446
Publication No. US20240349733A1
GENERAL INFORMATION
APPLICANT: THE TEXAS A&M UNIVERSITY SYSTEM (en)
TITLE OF INVENTION: Development of Specifically Targeted Binders and Antimicrobial Peptides (STAMPs) to Control Candidatus Liberibacter spp. (en)
FILE REFERENCE: TAM.156XC1
CURRENT APPLICATION NUMBER: US/18/644,446
CURRENT FILING DATE: 2024-04-24
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 28
LENGTH: 83
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..83
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 122; Length 83;
Best Local Similarity 100.0%;
Matches 25; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SRNSSIALGLRRAYAVFNYFVARGI 25
|||||||||||||||||||||||||
Db 59 SRNSSIALGLRRAYAVFNYFVARGI 83
RESULT 6
US-10-794-784-8
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 8, US/10794784
Publication No. US20070243580A9
GENERAL INFORMATION
APPLICANT: Jean-Louis Ruelle
TITLE OF INVENTION: BASB019 Proteins and Genes from
TITLE OF INVENTION: Moraxella Catarrhalis Antigens, Antibodies, and Uses
FILE REFERENCE: BM45311
CURRENT APPLICATION NUMBER: US/10/794,784
CURRENT FILING DATE: 2004-03-05
PRIOR APPLICATION NUMBER: US/09/674,779
PRIOR FILING DATE: 2001-01-03
PRIOR APPLICATION NUMBER: PCT/EP/99/03038
PRIOR FILING DATE: 1999-05-03
PRIOR APPLICATION NUMBER: GB9809683.7
PRIOR FILING DATE: 1998-05-06
NUMBER OF SEQ ID NOS: 14
SEQ ID NO 8
LENGTH: 172
TYPE: PRT
ORGANISM: Moraxella catarrhalis
Query Match 50.8%; Score 62; Length 172;
Best Local Similarity 52.0%;
Matches 13; Conservative 6; Mismatches 6; Indels 0; Gaps 0;
Qy 1 SRNSSIALGLRRAYAVFNYFVARGI 25
|| :::|| ||| || || :::||
Db 113 SREYNMSLGERRAVAVRNYLLSKGI 137
RESULT 7
US-10-603-108-3190
Sequence 3190, US/10603108
Publication No. US20070010665A1
GENERAL INFORMATION
APPLICANT: Gary L. Breton
TITLE OF INVENTION: NUCLEIC ACID AND AMINO ACID SEQUENCES RELATING TO MORAXELLA CATARRHALIS
TITLE OF INVENTION: FOR DIAGNOSTICS AND THERAPEUTICS
FILE REFERENCE: PATH03-14
CURRENT APPLICATION NUMBER: US/10/603,108
CURRENT FILING DATE: 2003-06-24
PRIOR APPLICATION NUMBER: US 09/540,263
PRIOR FILING DATE: 2000-04-04
PRIOR APPLICATION NUMBER: US 60/125,416
PRIOR FILING DATE: 1999-04-09
NUMBER OF SEQ ID NOS: 3840
SEQ ID NO 3190
LENGTH: 152
TYPE: PRT
ORGANISM: M.catarrhalis
Query Match 50.0%; Score 61; Length 152;
Best Local Similarity 52.0%;
Matches 13; Conservative 5; Mismatches 7; Indels 0; Gaps 0;
Qy 1 SRNSSIALGLRRAYAVFNYFVARGI 25
|| :::|| ||| || || : :||
Db 93 SREYNMSLGERRAVAVRNYLLGKGI 117
Regarding elected SEQ ID NO: 33, there appears to be a dearth of description of homolog amino acid sequences that would be expected to have the peptide binding function. For example, there is an identity gap exhibited below in sequential search results of SEQ ID NO: 28 (which is a sequence from the instant application comprising seq id no: 14), and the next most similar sequence showing about 90% identity to a sequence of an unrelated invention of compositions and methods for the treatment of pierce's disease:
RESULT 5
US-18-644-446-28
Sequence 28, US/18644446
Publication No. US20240349733A1
GENERAL INFORMATION
APPLICANT: THE TEXAS A&M UNIVERSITY SYSTEM (en)
TITLE OF INVENTION: Development of Specifically Targeted Binders and Antimicrobial Peptides (STAMPs) to Control Candidatus Liberibacter spp. (en)
FILE REFERENCE: TAM.156XC1
CURRENT APPLICATION NUMBER: US/18/644,446
CURRENT FILING DATE: 2024-04-24
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 28
LENGTH: 83
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..83
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 304; Length 83;
Best Local Similarity 100.0%;
Matches 52; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GIFSSRKCKTPSKTFKGICTRDSNCDTSCRYEGYPAGDCKGIRRRCLCCTHT 52
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GIFSSRKCKTPSKTFKGICTRDSNCDTSCRYEGYPAGDCKGIRRRCLCCTHT 52
RESULT 6
US-10-846-172A-3
(NOTE: this sequence has 31 duplicates in the database searched.
See complete list at the end of this report)
Sequence 3, US/10846172A
Publication No. US20050257285A1
GENERAL INFORMATION
APPLICANT: Los Alamos National Laboratory
APPLICANT: Gupta, Goutam
TITLE OF INVENTION: Compositions and Methods for the Treatment of Pierce's Disease
FILE REFERENCE: S-102,340
CURRENT APPLICATION NUMBER: US/10/846,172A
CURRENT FILING DATE: 2004-05-14
NUMBER OF SEQ ID NOS: 10
SEQ ID NO 3
LENGTH: 52
TYPE: PRT
ORGANISM: Spinachia oleracea
Query Match 90.5%; Score 275; Length 52;
Best Local Similarity 97.9%;
Matches 47; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GIFSSRKCKTPSKTFKGICTRDSNCDTSCRYEGYPAGDCKGIRRRCLC 48
||||||||||||||||||||||||||||||||||||||||||||||:|
Db 1 GIFSSRKCKTPSKTFKGICTRDSNCDTSCRYEGYPAGDCKGIRRRCMC 48
The instant specification fails to teach the necessary structure function relationship for homologs of the recited SEQ ID NOs in claims 5, 8, and 9 to have the function of peptide binding and/ or antimicrobial property. There is a dearth of description in the prior art of the structural requirements of homologs that would be expected to have the required peptide binding and antimicrobial activity function. As such, the specification fails to provide an adequate written description to support homologs of the recited SEQ ID NOs I claims 5, 8, and 9 that are able to effectively confer the function of peptide binding and antimicrobial activity. The limited examples of homologs described above do not describe the claimed genus by virtue of example. Therefore, one of ordinary skill in the art would not have recognized the Applicant to be in possession of the claimed invention at the time the application was filed.
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.
Claims 1, 3, 5,7-8, 10, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (Wang, H. (2021). A Molecular-Dynamics-Simulation-Based Drug Discovery Platform for Pathogenic Bacteria (Doctoral dissertation)), Eckert (US Patent No. US-9597407-B2), Overly (Overly Cottom, C., Stephenson, R., Wilson, L., & Noinaj, N. (2023). Targeting BAM for novel therapeutics against pathogenic Gram-negative bacteria. Antibiotics, 12(4), 679), Wang(b) (Wang, X., Peterson, J. H., & Bernstein, H. D. (2021). Bacterial outer membrane proteins are targeted to the bam complex by two parallel mechanisms. MBio, 12(3), 10-1128), and Uniprot Accession No. C6XF68 (Uniprot Accession No. C6XF68, version 68, published online 02/22/2023).
This is a modified rejection from the previous rejection set forth in the Office Action dated 11/18/2025, necessitated by Applicant’s amendments.
Claim 1 is drawn to a peptide comprising a protein binding sequence linked to an antimicrobial peptide sequence by a serine-glycine linker sequence, wherein the protein binding sequence binds to a surface protein on a cell of a plant pathogen, wherein the plant pathogen is a Candidatus Liberibacter sp.
Claim 3 is drawn to the peptide of claim 1, wherein the Candidatus Liberibacter sp. is Candidatus Liberibacter asiaticus, Candidatus Liberibacter africanus, or Candidatus Liberibacter americanus.
Claim 5 is drawn to the peptide of claim 1, wherein the antimicrobial peptide sequence is SOD12, according to SEQ ID NO: 32; SOD2*, according to SEQ ID NO: 33; SOD8, according to SEQ ID NO: 45; SOD9, according to SEQ ID NO: 46; SOD10, according to SEQ ID NO: 47; SOD11, according to SEQ ID NO: 48; SOD13, according to SEQ ID NO: 49; AGM176, according to SEQ ID NO: 50; AGM179, according to SEQ ID NO: 51; MaSAM, according to SEQ ID NO: 52; Plantaricin JLA-9, according to SEQ ID NO: 53; Darobactin, according to SEQ ID NO: 54; Urechistachykinin II, according to SEQ ID NO: 55, or a homolog thereof.
Claim 7 is drawn to the peptide of claim 1, wherein the linker sequence is GGSGGS (SEQ ID NO: 34) or a homolog thereof.
Claim 8 is drawn to the peptide of claim 1, wherein the protein binding sequence is BamA_27401 according to SEQ ID NO: 2; BamA_22602, according to SEQ ID NO: 3; BamA_02401, according to SEQ ID NO: 4; BamA_01403 according to SEQ ID NO: 5; BamA_10701, according to SEQ ID NO: 6; BamA_03001, according to SEQ ID NO: 7; BamA_03501, according to SEQ ID NO: 8; BamA_46301, according to SEQ ID NO: 9; BamA_00901, according to SEQ ID NO: 10; BamA_00902, according to SEQ ID NO: 11; BamA_56973, according to SEQ ID NO: 12; BamA_56869, according to SEQ ID NO: 13; BamA_57020, according to SEQ ID NO: 14; peptide 1, according to SEQ ID NO: 15; peptide 9, according to SEQ ID NO: 16; peptide 10, according to SEQ ID NO: 17; peptide 11, according to SEQ ID NO: 18; peptide 12, according to SEQ ID NO: 19; peptide 18, according to SEQ ID NO: 20; ACT56973.1, according to SEQ ID NO: 29; ACT56869.1, according to SEQ ID NO: 30; ACT57020.1, according to SEQ ID NO: 31, or a homolog thereof.
Claim 10 is drawn to the peptide of claim 1, wherein the protein binding sequence binds to a BamA protein on the surface of the plant pathogen cell.
Claim 16 is drawn to a method of controlling and/or treating a plant pathogen infection in a plant comprising applying the peptide of claim 1 to the plant or an environment around the plant.
Regarding claim 1, Wang teaches identifying multiple antimicrobial peptide sequences (AMPs), including e.g. darobactin, plantaricin JLA-9, and urechistachykinin II (p. 70, Table 9), which bind to the TolC outer membrane protein of Candidatus liberibacter (p. 62-64, 69-70, 72). Thus, Wang teaches an antimicrobial peptide sequence that binds to a surface protein on a cell of a plant pathogen, wherein the plant pathogen is a Candidatus Liberibacter sp.
Regarding claim 3, Wang teaches wherein the Candidatus Liberibacter sp. is Candidatus Liberibacter asiaticus (p. 62).
Regarding claim 5, Wang teaches the screened darobactin antimicrobial peptide had a peptide sequence of WNWSKSF, which is 100% sequence identity to instant SEQ ID NO: 54 (p. 70, Table 9). Wang teaches the screened plantaricin JLA-9 antimicrobial peptide had a peptide sequence of FWQKMSFA, which is 100% sequence identity to instant SEQ ID NO: 53 (p. 70, Table 9).
However, Wang does not explicitly teach:
wherein a protein binding sequence is linked to the antimicrobial peptide sequence(s) by a serine-glycine linker sequence, wherein it is the protein binding sequence binds to a surface protein on a cell of a plant pathogen (remaining limitation of claim 1).
The limitations of 7-8, 10, and 16 as recited above.
Regarding the remaining limitation of claim 1, in analogous art, Eckert teaches an invention related to specifically targeted anti-microbial peptides (STAMPs), wherein a targeting moiety is attached to the antimicrobial peptide and the targeting moiety binds to a microorganism, e.g. bacterium (abstract, Col. 1, lines 55-58, Col. 14, lines 7-11). Eckert teaches the targeting moiety may be attached to effector/ anti-microbial peptide via a peptide linker such as those found in Table 16 (Col. 2, lines 43-54, claim 1 of Eckert). The list of peptide linkers includes GGSGGS (i.e. a serine-glycine linker) (Col. 426, Table 16, and claim 5 of Eckert). In other analogous art, Overly teaches β-barrel assembly machinery (BAM) is conserved and essential across all Gram-negative bacteria (abstract), BamA is the most conserved subunit (p. 3, ¶1), and since BAM (more specifically BamA) is conserved across bacterial species, there is promise for the development of broad spectrum novel antibiotics which can treat a wide range of bacterial infections (p. 4, ¶3). In other analogous art, Wang(b) teaches a conserved “β signal” motif is located at the C terminus of the β barrel of many outer membrane proteins (OMPs) (abstract) and allows for binding of OmpA to BamA (p. 2, ¶3- p. 3, ¶2, p. 12, discussion section). Additionally, Uniprot Accession No. C6XF68 teaches the Candidatus Liberibacter asiaticus-derived OmpA amino acid sequence that comprises a sequence with 100% sequence identity to instant SEQ ID NO: 14. Uniprot Accession No. C6XF68 further annotates (feature viewer) the sequence that makes up the C-terminus β-barrel, which is 100% identical to instant SEQ ID NO: 14.
Regarding claim 7, Eckert teaches the targeting moiety may be attached to effector/ anti-microbial peptide via a peptide linker such as those found in Table 16 (Col. 2, lines 43-54, claim 1 of Eckert). The list of peptide linkers includes GGSGGS (i.e. a serine-glycine linker) (Col. 426, Table 16, and claim 5 of Eckert).
Regarding claim 8, as described above, Uniprot Accession No. C6XF68 teaches the Candidatus Liberibacter asiaticus-derived OmpA amino acid sequence that comprises a sequence with 100% sequence identity to instant SEQ ID NO: 14. Uniprot Accession No. C6XF68 further annotates (feature viewer) the sequence that makes up the C-terminus β-barrel, which is 100% identical to instant SEQ ID NO: 14.
Regarding claim 10, as described above, In other analogous art, Overly teaches β-barrel assembly machinery (BAM) is conserved and essential across all Gram-negative bacteria (abstract), BamA is the most conserved subunit (p. 3, ¶1), and since BAM (more specifically BamA) is conserved across bacterial species, there is promise for the development of broad spectrum novel antibiotics which can treat a wide range of bacterial infections (p. 4, ¶3). In other analogous art, Wang(b) teaches a conserved “β signal” motif is located at the C terminus of the β barrel of many outer membrane proteins (OMPs) (abstract) and allows for binding of OmpA to BamA (p. 2, ¶3- p. 3, ¶2, p. 12, discussion section). Additionally, Uniprot Accession No. C6XF68 teaches the Candidatus Liberibacter asiaticus-derived OmpA amino acid sequence that comprises a sequence with 100% sequence identity to instant SEQ ID NO: 14. Uniprot Accession No. C6XF68 further annotates (feature viewer) the sequence that makes up the C-terminus β-barrel, which is 100% identical to instant SEQ ID NO: 14.
Regarding claim 16, Eckert teaches various embodiments of methods of disinfecting a surface including contacting the surface with one or more of the antimicrobial peptides described in Eckert’s invention, wherein the surface is a plant (Col. 9, lines 15-18 and 36-39).
It would therefore be obvious to combine the teachings of Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 to arrive at the instantly claimed method with a reasonable expectation of success because Wang teaches specific antimicrobial peptides that may be used to treat Candidatus Liberibacter- caused disease in citrus (p. 64) and Eckert teaches a surface protein- targeting moiety may be linked to the AMPs via serine-glycine linkers, termed STAMPs (abstract, Col. 1, lines 55-58, Col. 14, lines 7-11, claims 1 and 5 of Eckert). Furthermore, Overly teaches BamA is a highly conserved subunit (p. 3, ¶1) in all gram negative bacteria , and Wang(b) teaches the β signal in the β barrel at the C-terminus of bacterial OMPs binds BamA (p. 2, ¶3- p. 3, ¶2, p. 12, discussion section). Additionally, the β barrel at the C-terminus of Candidatus Liberibacter asiaticus-derived OmpA is annotated and a known and readily available sequence. Therefore, incorporating the known OmpA sequence (to bind the a surface protein of Candidatus Liberibacter asiaticus) and a known antimicrobial peptide taught to be effective against Candidatus Liberibacter into the STAMP peptide/ method taught by Eckert could be achieved by one of ordinary skill in the art without encountering any special technical difficulty. Because Overly teaches binding an antimicrobial peptide to BamA inhibits its function, the resulting STAMP with the Amp linked to the OmpA sequence that binds BamA would also reasonably be expected to inhibit its function. One having ordinary skill in the art would have been motivated to combine the teachings for the purpose of binding an antimicrobial peptide to BamA using an alternative, known and readily available sequence for same purpose of inhibiting BamA function to treat bacterial infections as taught by Overly (p. 4, ¶3, Table 2, p. 11, ¶1), and specifically Candidatus Liberibacter asiaticus-caused HLB as taught by Wang (p. 64).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 as applied to claim 1 above, and further in view of Mirkov (US-10640784-B2).
This is a modified rejection from the previous rejection set forth in the Office Action dated 11/18/2025, necessitated by Applicant’s amendments.
Claim 9 is drawn to the peptide of claim 1, where the peptide is 22602-SOD12, according to SEQ ID NO: 21; SOD12-22602, according to SEQ ID NO: 22; 57020-SOD12, according to SEQ ID NO: 23; SOD12-57020, according to SEQ ID NO: 24; 22602-SOD2*, according to SEQ ID NO: 25; SOD2*-22602, according to SEQ ID NO: 26; 57020-SOD2*, according to SEQ ID NO: 27; SOD2*-57020, according to SEQ ID NO: 28; AMP1_ACT56869.1_241-255, according to SEQ ID NO: 58; AMP1_ACT56973.1_80-96, according to SEQ ID NO: 59; AMP1_ACT57020.1_94-118, according to SEQ ID NO: 60; AMP2_ACT56869.1_241-255, according to SEQ ID NO: 61; AMP2_ACT56973.1_80-96, according to SEQ ID NO: 62; AMP2_ACT57020.1_94-118, according to SEQ ID NO: 63; or a homolog thereof.
Regarding claim 9, Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 teach the limitations of claim 1 as set forth in the previous obviousness rejection. The teachings of Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 as they are applied to claim 1 are set forth previously herein and are incorporated by reference.
However, Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 do not explicitly teach the limitation(s) of claim 9 as recited above.
In analogous art, Mirkov teaches a defensin peptide sequence (SEQ ID NO: 32 of Mirkov) comprising a sequence with 100% sequence identity to instant SEQ ID NO: 33 and has antimicrobial activity in citrus plants (claims 1 and 8 of Mirkov), specifically citrus Huanglongbing caused by Candidatus Liberibacter asiaticus (Col. 5, lines 44-67).
RESULT 1
US-15-212-041B-32
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 32, US/15212041B
Patent No. 10640784
GENERAL INFORMATION
APPLICANT: TEXAS A&M UNIVERSITY SYSTEMS
APPLICANT: MIRKOV, Erik T.
APPLICANT: MANDADI, Kranthi Kiran
TITLE OF INVENTION: PATHOGEN RESISTANT CITRUS COMPOSITIONS, ORGANISMS, SYSTEMS, AND
TITLE OF INVENTION: METHODS
FILE REFERENCE: 10003183-50235311
CURRENT APPLICATION NUMBER: US/15/212,041B
CURRENT FILING DATE: 2016-07-15
PRIOR APPLICATION NUMBER: US 62/192,732
PRIOR FILING DATE: 2015-07-15
NUMBER OF SEQ ID NOS: 102
SEQ ID NO 32
LENGTH: 60
TYPE: PRT
ORGANISM: Spinacia oleracea
FEATURE:
NAME/KEY: mat_peptide
LOCATION: (1)..(60)
OTHER INFORMATION: Def1 peptide
Query Match 100.0%; Score 304; Length 60;
Best Local Similarity 100.0%;
Matches 52; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GIFSSRKCKTPSKTFKGICTRDSNCDTSCRYEGYPAGDCKGIRRRCLCCTHT 52
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9 GIFSSRKCKTPSKTFKGICTRDSNCDTSCRYEGYPAGDCKGIRRRCLCCTHT 60
Because SEQ ID NO: 32 of Mirkov comprises a sequence with 100% sequence identity and SEQ ID NO: 32 of Mirkov has only an additional 8 bp at the terminal end and also has antimicrobial activity in citrus plants, SEQ ID NO: 32 of Mirkov is reasonably interpreted as a homolog of instant SEQ ID NO: 33.
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention taught by Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 to include the limitations of Mirkov to arrive at the instantly claimed method with a reasonable expectation of success because Mirkov teaches other known antimicrobial peptides used to treat HLB in citrus (claims 1, 8 of Mirkov, Col. 5, lines 44-67) and using one antimicrobial peptide sequence known to be effective against Candidatus Liberibacter in place of another known sequence could be achieved by one of ordinary skill in the art without encountering any special technical difficulties. One having ordinary skill in the art would have been motivated to combine the teachings for the purpose of binding a Candidatus Liberibacter antimicrobial peptide to BamA using an alternative, known and readily available antimicrobial peptide sequence for the same purpose of inhibiting BamA function to treat bacterial infections as taught by Overly (p. 4, ¶3, Table 2, p. 11, ¶1), and specifically Candidatus Liberibacter asiaticus-caused HLB as taught by Wang (p. 64) and Mirkov (Col. 5, lines 44-67). The combination of the Amp taught by Mirkov (homolog of instant SEQ ID NO: 33), the linker taught by Eckert (instant SEQ ID NO: 34), and the Candidatus Liberibacter asiaticus-derived β signal of OmpA (instant SEQ ID NO: 14) would generate a homolog of instant SEQ ID NO: 27 and 28, depending the orientation of the linked sequences. For the reasons above, claim 9 is obvious in view of the prior art.
Claims 11-2 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 as applied to claim 1 above, and further in view of Sastoque (US-20210144998-A1).
This is a modified rejection from the previous rejection set forth in the Office Action dated 11/18/2025, necessitated by Applicant’s amendments.
Claim 11 is drawn to a composition comprising the peptide of claim 1 and an agriculturally acceptable carrier.
Claim 12 is drawn to the composition of claim 11, further comprising an agriculturally acceptable solvent.
Claim 14 is drawn to the composition of claim 11, wherein the agriculturally acceptable carrier is water.
Claim 15 is drawn to the composition of claim 11, wherein the peptide is at a concentration of about 5 μg/ml to about 500 μg/ml
Regarding claims 11-12 and 14-15, Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 teach the limitations of claim 1 as set forth in the previous obviousness rejection. The teachings of Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 as they are applied to claim 1 are set forth previously herein and are incorporated by reference.
However, Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 do not explicitly teach:
a composition comprising the peptide of claim 1 and an agriculturally acceptable carrier (claim 11).
the composition of claim 11, further comprising an agriculturally acceptable solvent (claim 12).
the composition of claim 11, wherein the agriculturally acceptable carrier is water (claim 14).
The composition of claim 11, wherein the peptide is at a concentration of about 5 μg/ml to about 500 μg/ml (claim 15).
In analogous art, Sastoque teaches compositions and methods for treating huanglongbing disease in citrus (title).
Regarding claims 11 and 14, Sastoque teaches compositions of the invention comprise agriculturally acceptable carriers which are a natural or synthetic, organic or inorganic substance which is mixed or combined with the active agents for better applicability, in particular for application to citrus plants (¶0013, 0015). The carrier is generally inert and should be suitable for use in agriculture, and non-limiting examples of carriers include water, alcohols (such as ethanol, propanol or butanol), organic solvents, mineral and vegetable oils, and derivatives thereof (¶0015).
Regarding claim 12, Sastoque teaches the compositions of the invention may also comprise agriculturally acceptable solvents (¶0013-0014).
Regarding claim 15, Sastoque teaches each active ingredient can be present in an amount ranging between .01 g per liter to 100 g per liter, and in the second narrowest embodiment that each active ingredient can be present in an amount ranging between 0.5 to 1.5 g per liter (500 µg/mL converts to 0.5 g/1L) (¶0019).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention taught by Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 to include the limitations of Sastoque to arrive at the instantly claimed method with a reasonable expectation of success because Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 teaches antimicrobial peptides, binding peptides, and STAMPs for use against Candidatus Liberibacter, and Sastoque similarly teaches about compositions to treat treating huanglongbing disease in citrus (title) caused by Candidatus Liberibacter and further teaches the composition can be applied via foliar spray, soil drench, or injection. One having ordinary skill in the art could include the antimicrobial peptides into the composition and application method of Sastoque without encountering any special technical obstacles One having ordinary skill in the art would have been motivated to do so because the antimicrobial peptides would require application to the plant to be effective, and Sastoque teaches multiple methods of application. Additionally, one having ordinary skill in the art would have been motivated to combine the teachings because the composition taught by Sastoque effectively treats HLB, and it would be prima facie obvious to use one or both of the compositions for the same purpose of treating HLB caused by Candidatus Liberibacter.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 and Sastoque as applied to claims 1, 11, and 12 above, and further in view of Schaefer (Schaefer, B. (2023). Understanding the Industrial Uses of Acetonitrile, Lab Pro Blogs).
This is a modified rejection from the previous rejection set forth in the Office Action dated 11/18/2025, necessitated by Applicant’s amendments.
Claim 13 is drawn to the composition of claim 12, wherein the agriculturally acceptable solvent is acetonitrile.
Regarding claim 13, Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 and Sastoque teach the limitations of claims 1, 11, and 12 as set forth in the previous obviousness rejection. The teachings of Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 and Sastoque as they are applied to claims 1, 11, and 12 are set forth previously herein and are incorporated by reference.
However, Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 and Sastoque do not explicitly teach:
The composition of claim 12, wherein the agriculturally acceptable solvent is acetonitrile (claim 13).
In analogous art, Schaefer teaches acetonitrile is another known organic solvent widely used in the production of agrochemicals (p. 2).
It would therefore have been obvious to a person of ordinary skill in the art to
modify the invention of as taught by Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 and Sastoque to include the acetonitrile organic solvent taught by Schaefer to arrive at the instantly claimed method with a reasonable expectation of success because the organic solvent taught by Schaefer was a known and readily obtainable organic solvent, and was known to be used in the production of agrochemicals (p. 2) and capable of dissolving a wide variety of materials (p. 3). One having ordinary skill in the art would have been motivated to combine the teachings because it would have been prima facie obvious to substitute any of the known organic solvents taught by Sastoque with another organic solvent known in the art, acetonitrile, for the same purpose.
Claims 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 as applied to claims 1 and 16 above, and further in view of Sastoque (US-20210144998-A1).
This is a modified rejection from the previous rejection set forth in the Office Action dated 11/18/2025, necessitated by Applicant’s amendments.
Claim 17 is drawn to the method of claim 16, wherein the composition is applied as a foliar spray, injection into the phloem, trunk feeding, or via irrigation.
Claim 18 is drawn to the method of claim 16, wherein the plant is an orange tree, a lemon tree, a lime tree, a grapefruit tree, a clementine tree, a tangerine tree, a tangelo tree, a pomelo tree, or a potato plant.
Claim 19 is drawn to the method of claim 16, wherein the plant pathogen is a Candidatus Liberibacter sp.
Claim 20 is drawn to the method of claim 19, wherein the Candidatus Liberibacter sp. is Candidatus Liberibacter asiaticus, Candidatus Liberibacter africanus, or Candidatus Liberibacter americanus.
Regarding claims 17-20, Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 teach the limitations of claims 1 and 16 as set forth in the previous obviousness rejection. The teachings of Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 as they are applied to claims 1 and 16 are set forth previously herein and are incorporated by reference. Additionally, Wang teaches the purpose of screening for affective antimicrobial peptides against Candidatus Liberibacter asiaticus, which causes citrus greening or HLB disease, is to provide treatment for the disease in citrus trees (p. 62, introduction, ¶1).
However, Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 do not explicitly teach:
the method of claim 16, wherein the composition is applied as a foliar spray, injection into the phloem, trunk feeding, or via irrigation (claim 17).
the method of claim 16, wherein the plant is an orange tree, a lemon tree, a lime tree, a grapefruit tree, a clementine tree, a tangerine tree, a tangelo tree, a pomelo tree, or a potato plant (claim 18).
the method of claim 16, wherein the plant pathogen is a Candidatus Liberibacter sp. (claim 19).
the method of claim 19, wherein the Candidatus Liberibacter sp. is Candidatus Liberibacter asiaticus, Candidatus Liberibacter africanus, or Candidatus Liberibacter americanus (claim 20).
In analogous art, Sastoque teaches compositions and methods for treating huanglongbing disease in citrus (title).
Regarding claim 17, Sastoque teaches methods for controlling and/or treating citrus greening disease in citrus plants comprising the administration of a composition comprising of active agents and compounds taught by Sastoque’s invention to the citrus plant by foliar spray, injection into the phloem, or drench application to the root system (¶0042).
Regarding claim 17, Sastoque teaches the citrus plant may be an orange, a lemon, a lime, a grapefruit, a clementine, a tangerine, a tangelo or a pomelo tree (¶0041).
Regarding claims 19-20, Sastoque teaches the compositions and methods are for treating huanglongbing (HLB) disease in citrus (title), which is caused by the phloem-limited fastidious prokaryotic α-proteobacterium Candidatus Liberibacter spp., africanus, and L. americanus. (¶0002).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention taught by Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 to include the limitations of Sastoque to arrive at the instantly claimed method with a reasonable expectation of success because Wang teaches identified antimicrobial peptides (AMPs) that bind surface proteins of a Candidatus liberibacter for HLB management in citrus (p. 63, 81), Eckert teaches disinfecting a plant surface by contacting the surface with one or more of the antimicrobial peptides (Col. 9, lines 15-18 and 36-39), and Sastoque provides a more explicit method of applying/contacting a composition to citrus plants to treat HLB caused by Candidatus Liberibacter (¶0002, 0042). One having ordinary skill in the art could apply the antimicrobial peptides taught by Wang to citrus plants to treat HLB caused by Candidatus Liberibacter using the application methods taught by Sastoque without encountering any special technical difficulties. One having ordinary skill in the art would have been motivated to do so because both Wang and Sastoque teach approaches to manage HLB in citrus, and Sastoque teaches how to produce and apply HLB-treatments compositions. It would therefore be obvious to include the STAMPs taught by Wang, Eckert, Overly, Wang(b), and Uniprot Accession No. C6XF68 in the composition of Sastoque (either as the only treatment agent or in combination with the active agents and compounds taught by Sastoque) with the spray, injection, or drench application method of Sastoque for the same purpose of managing Candidatus Liberibacter-caused HLB disease in citrus.
Response to Arguments
Applicant argues beginning on p. 5 of remarks dated 02/18/2026 the
following arguments:
Claims 5, 8, and 9 are rejected under 35 U.S.C. § 112(a) as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the claimed invention. Applicant respectfully disagrees and asserts that there is an adequate written description in the subject specification to convey to the ordinarily skilled artisan that they had possession of the claimed invention.
The Office Action alleges that the application lacks a written description of the required structure in any homolog necessary for the sequences to maintain the function of an antimicrobial and/or protein binding peptide. Applicant respectfully disagrees.
The as-filed application defines "homologs of amino acid sequences" to mean any amino acid sequence obtained by mutagenesis of the nucleic acid sequence that encodes the amino acid sequence" and "exhibiting modifications in relation to the parent sequences." Homologs, according to the as-filed application, have substantially the same biological activity as the corresponding reference amino acid sequence, i.e., an amino acid homologous to an antimicrobial peptide would encode for a peptide having the same biological activity as the corresponding protein encoded by the reference antimicrobial peptide. The as-filed application also teaches that particular nucleic acid sequences implicitly encompass conservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs, single nucleotide polymorphisms (SNPs), and complementary sequences as well as the sequence explicitly indicated (as-filed application, pages 11 and 12). Therefore, one skilled in the art recognized that Applicant was in possession of the subject matter recited in claims 5, 8, and 9. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 112 is respectfully requested.
This argument has been fully considered and is found not persuasive for
the following reason(s):
The specification very broadly defines homologous amino acid sequences” or “homologs of amino acid sequences”, reciting:
“The subject invention provides for the use of “homologous amino acid sequences” or “homologs of amino acid sequences”. Homologs of amino acid sequences will be understood to mean any amino acid sequence obtained by mutagenesis of the nucleic acid sequence that encodes the amino acid sequence according to techniques well known to persons skilled in the art, and exhibiting modifications in relation to the parent sequences. For example, mutations in the regulatory and/or promoter sequences for the expression of a polypeptide that result in a modification of the level of expression of a polypeptide according to the invention provide for a “homolog of an amino acid sequence”. Likewise, substitutions, deletions, or additions of nucleic acids encoding the polypeptides of the invention provide for “homologs” of amino acid sequences. In various embodiments, “homologs” of amino acid sequences have substantially the same biological activity as the corresponding reference amino acid sequence, i.e., an amino acid homologous to an antimicrobial peptide would encode for a peptide having the same biological activity as the corresponding protein encoded by the reference antimicrobial peptide. Typically, a homolog of an amino acid sequence shares a sequence identity with the reference or parent amino acid of at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%. These percentages are purely statistical and differences between two amino acid sequences can be distributed randomly and over the entire sequence length.”
Thus, homologs according to the broad definition also include amino acid sequence that share a sequence identity with the reference or parent amino acid of as little as 50%. The definition is very broad Applicant fails to describe any homolog that, e.g. has as little as 50% sequence identity to the recited SEQ ID NOs in the rejected claims, and maintains the function of an antimicrobial and/or protein binding peptide.
For this reason and those set forth in the written description rejection, the claims remain rejected under 35 USC 112(a).
Applicant argues beginning on p. 6 of remarks dated 02/18/2026 the
following arguments:
Claims 1, 2, 3, and 10 are rejected under 35 U.S.C. § 101 as directed to a judicial exception. Applicant respectfully disagrees and asserts that the as-filed claims are not directed to a judicial exception. Without conceding the correctness of the rejection, and solely to advance prosecution, claim 1 has been amended to recite a peptide comprising a protein binding sequence linked to an antimicrobial peptide sequence by a serine-glycine linker sequence, wherein the protein binding sequence binds to a surface protein on a cell of a plant pathogen, and wherein the plant pathogen is a Candidatus Liberibacter sp. Such a peptide does not occur in nature. Thus, claim 1 is directed to patent-eligible subject matter. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 101 is respectfully requested.
Examiner’s response:
In view of Applicant’s amendments, the rejections under 35 USC 101 have been withdrawn.
Applicant argues beginning on p. 6 of remarks dated 02/18/2026 the
following arguments:
Claims 1-5 are rejected under 35 U.S.C. § 102(a)(1) as anticipated by Wang (2021). Applicant respectfully disagrees and asserts that the reference does not anticipate the claimed invention.
A claim is anticipated if each and every element, arranged as in the claim, is found in a single prior art reference. See Arbutus Biopharma Corp. v. Modernatx, Inc., 65 F.4th 656, 662-63 (Fed. Cir. 2023). Here, the Wang dissertation does not teach a peptide comprising a protein binding sequence linked to an antimicrobial peptide sequence by a serine-glycine linker sequence, wherein the protein binding sequence binds to a surface protein on a cell of a plant pathogen, wherein the plant pathogen is a Candidatus Liberibacter sp. Instead, Wang teaches peptides that both bind and inhibit a function of Candidatus Liberibacter spp. Wang does not teach two separate peptide sequences for binding and inhibiting Candidatus Liberibacter spp. and Wang does not teach that these two separate sequences are connected through a serine-glycine linker sequence. In fact, Wang does not even teach or suggest which amino acids of its peptides are associated with a particular function and, as acknowledged by the Office Action, Wang does not teach any linkers. Therefore, Wang does not teach each and every element of the claims and does not anticipate the claims. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 102(a)(1) is respectfully requested.
This argument has been fully considered and is found not persuasive for
the following reason(s):
In view of Applicant’s amendments, the rejections under 35 USC 102 have been withdrawn. However, in view of Applicant’s amendments the claims are rejected under 35 USC 103 (see rejection above).
Applicant argues beginning on p. 6 of remarks dated 02/18/2026 the
following arguments:
Claims 6-7 and 16 are rejected under 35 U.S.C. § 103 as obvious over Wang (2021) as applied to claims 1 and 4 above, and further in view of Eckert et al. (U.S. Patent No. 9,597,407). Applicant respectfully disagrees and asserts that the claimed invention is not obvious over the cited references.
The Office Action acknowledges that Wang does not teach a linker sequence or applying a peptide to a plant or an environment around the plant to control and/or treat a plant pathogen infecting a plant. Eckert is cited as teaching peptides wherein a targeting moiety is attached to an antimicrobial peptide, linkers, and methods of disinfecting a surface and that the surface can be a plant.
To establish obviousness, the Office must demonstrate "that a skilled artisan would have been motivated to combine the teachings of the prior art references to achieve the claimed invention, and that the skilled artisan would have had a reasonable expectation of success in doing so." Eli Lilly & Co. v. Teva Pharms. Int'l GmbH, 8 F.4th 1331, 1344 (Fed. Cir. 2021). "It is not sufficient to merely allege that the individual elements of the claimed invention were each known in the prior art," there must be "an apparent reason to combine known elements in the fashion claimed." KSR Int'l. Co. v. Teleflex Inc., 550 U.S. 398, 418-19 (2007). As the Federal Circuit has since explained, "obviousness concerns whether a skilled artisan not only could have made but would have been motivated to make the combinations or modifications of prior art to arrive at the claimed invention." Belden Inc. v. Berk-TekLLC, 805 F.3d 1064, 1073 (Fed. Cir. 2015) (emphasis in original).
Here, one skilled in the art would not have been motivated to combine Wang and Eckert because the peptides disclosed in the two references are structurally distinct single peptides performing binding and antimicrobial functions in Wang and peptide chimeras containing two or more peptides, some of which perform binding and others perform antimicrobial functions in Eckert. None of the references provides any guidance on how to make a two-peptide chimera. Based on the teachings of the cited references, one skilled in the art would not be motivated to use Wang's peptides as either a protein binding or antimicrobial sequences because Wang does not teach which of its disclosed peptide sequences perform the different functions. Furthermore, the skilled artisan would not be motivated to add a protein binding peptide or an antimicrobial peptide to any of Wang's peptides because the skilled artisan would not know whether such chimeras would, or could, bind to a surface protein of Candidatus Liberibacter spp. as required by the claims. "It is bedrock law that the inquiry of motivation and reasonable expectation of success must focus on arriving at the claimed invention []." Janssen v. Teva, 141 F.4th 1367, 1379 (Fed. Cir. 2025) (emphasis in original). Notably, Eckert does not disclose any sequences having the ability to bind to Candidatus Liberibacter in its extensive list of targeting peptides (Eckert, pages 32-110; SEQ ID NOs: 13-1028). Furthermore, a skilled artisan would not look to transform Wang's peptides into chimeric peptides where Wang already taught that their peptides performed both the binding and antimicrobial function well (Wang, page 72, first paragraph; page 80, last paragraph; page 81, second full paragraph). The Court of Appeals for the Federal Circuit has held, in In re Omeprazole Patent Litigation, 536 F.3d 1361 (Fed. Cir. 2008), that even though all the individual pieces of the claimed invention were known separately in the prior art, and even though there was no evidence of undue technical hurdles or lack of a reasonable expectation of success, an invention may, nevertheless, be found non-obvious because no flaws or problems had been recognized which might prompt the modifications necessary to arrive at a claimed invention. In this case, since Wang already teaches that the disclosed peptides had both binding and antimicrobial activity, there would have been no motivation to create chimeric proteins comprising two or more of the proteins disclosed in Wang. Thus, there was no reason to modify the prior art product even though the modification could technically have been done.
Finally, one skilled in the art would not be motivated to apply Wang's peptides to a plant to control and/or treat a plant pathogen infection based on Eckert, especially since Eckert teaches disinfecting a surface, including a plant, with completely different peptides, and one skilled in the art would not know whether any peptides disclosed in Wang had such an activity. Thus, the combined references do not render the claims obvious. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 103 is respectfully requested.
This argument has been fully considered and is found not persuasive for
the following reason(s):
The claims are now rejected by a modified rejection under 35 USC 103, necessitated by Applicant’s arguments.
Applicant first argues:
“Here, one skilled in the art would not have been motivated to combine Wang and Eckert because the peptides disclosed in the two references are structurally distinct single peptides performing binding and antimicrobial functions in Wang and peptide chimeras containing two or more peptides, some of which perform binding and others perform antimicrobial functions in Eckert. None of the references provides any guidance on how to make a two-peptide chimera. Based on the teachings of the cited references, one skilled in the art would not be motivated to use Wang's peptides as either a protein binding or antimicrobial sequences because Wang does not teach which of its disclosed peptide sequences perform the different functions.”
This is not persuasive because Eckert does teach how to make a two-peptide chimera that is a STAMP with an antimicrobial peptide linked to a targeting moiety/ targeted binding peptide by a linker, e.g. the serine-glycine linker GGSGGS (see rejection above). Additionally, darobactin taught by Wang is a generally known antimicrobial peptide (AMP) that also was the most effective AMP of those tested against Candidatus Liberibacter asiaticus (CLas). One of ordinary skill in the art would be motivated to use the AMP taught by Wang in the STAMP chimera peptide taught by Eckert because it was proven by Wang as effective against CLas.
Next, Applicant argues:
Furthermore, the skilled artisan would not be motivated to add a protein binding peptide or an antimicrobial peptide to any of Wang's peptides because the skilled artisan would not know whether such chimeras would, or could, bind to a surface protein of Candidatus Liberibacter spp. as required by the claims. "It is bedrock law that the inquiry of motivation and reasonable expectation of success must focus on arriving at the claimed invention []." Janssen v. Teva, 141 F.4th 1367, 1379 (Fed. Cir. 2025) (emphasis in original). Notably, Eckert does not disclose any sequences having the ability to bind to Candidatus Liberibacter in its extensive list of targeting peptides (Eckert, pages 32-110; SEQ ID NOs: 13-1028).
As described in the modified 103 rejection, a OmpA sequence that was known to bind to BamA which is highly conserved on all gram negative bacteria was known and readily available, and has 100% sequence identity to instant SEQ ID NO: 14. It would have been obvious to modify the STAMP of Eckert to include the AMP of Wang and the known and available binding peptide of SEQ ID NO: 14 for the purpose of producing a STAMP that targets and has antimicrobial activity against CLas which is the causal bacteria of citrus greening/ HLB. There is reasonable expectation of success that the chimera peptide would be effective and bind CLas because Overly teaches BamA is highly conserved on all gram-negative bacteria, Wang(b) teaches a conserved “β signal” motif is located at the C terminus of the β barrel of many outer membrane proteins (OMPs) (abstract) allows for binding of OmpA to BamA (p. 2, ¶3- p. 3, ¶2, p. 12, discussion section), and Uniprot Accession No. C6XF68 teaches the known OmpA amino acid sequence that comprises a sequence with 100% sequence identity to instant SEQ ID NO: 14 and further specifically annotates (feature viewer) the sequence that makes up the C-terminus β-barrel, which is 100% identical to instant SEQ ID NO: 14. Because Wang(b) teaches this sequences binds to BamA which is conserved on all gram-negative bacteria (which includes CLas), one would have a reasonable expectation of success that this peptide sequence would bind BamA on CLas.
Next, Applicant argues:
Furthermore, a skilled artisan would not look to transform Wang's peptides into chimeric peptides where Wang already taught that their peptides performed both the binding and antimicrobial function well (Wang, page 72, first paragraph; page 80, last paragraph; page 81, second full paragraph). The Court of Appeals for the Federal Circuit has held, in In re Omeprazole Patent Litigation, 536 F.3d 1361 (Fed. Cir. 2008), that even though all the individual pieces of the claimed invention were known separately in the prior art, and even though there was no evidence of undue technical hurdles or lack of a reasonable expectation of success, an invention may, nevertheless, be found non-obvious because no flaws or problems had been recognized which might prompt the modifications necessary to arrive at a claimed invention. In this case, since Wang already teaches that the disclosed peptides had both binding and antimicrobial activity, there would have been no motivation to create chimeric proteins comprising two or more of the proteins disclosed in Wang. Thus, there was no reason to modify the prior art product even though the modification could technically have been done.
This is not persuasive because, as described in the rejection and previous responses, BamA is a highly conserved outer membrane protein on all gram-negative bacteria. One of ordinary skill in the art would be motivated to combine a Uniprot binding peptide and the AMP of Wang into the STAMP model of Eckert for the purpose of targeting the conserved and vital BamA protein, rather than TolC.
Next, Applicant argues:
Finally, one skilled in the art would not be motivated to apply Wang's peptides to a plant to control and/or treat a plant pathogen infection based on Eckert, especially since Eckert teaches disinfecting a surface, including a plant, with completely different peptides, and one skilled in the art would not know whether any peptides disclosed in Wang had such an activity. Thus, the combined references do not render the claims obvious. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 103 is respectfully requested.
This is not persuasive because darobactin is a known AMP used against various bacteria and Wang teaches it is also an effective AMP against CLas. Additionally, the binding sequence was known and annotated, and described by Wang(b) to effectively bind BamA which is highly conserved on bacteria including CLas. Therefore, one of ordinary skill in the art would have a reasonable expectation of success that the AMP peptide would have AMP activity against CLas, and the binding peptide would effectively bind BamA on CLas.
Applicant argues beginning on p. 6 of remarks dated 02/18/2026 the
following arguments:
Claim 8 is rejected under 35 U.S.C. § 103 as obvious over Wang (2021) as applied to claim 1 above, and further in view of Eckert et al. (U.S. Patent No. 9,597,407), Overly Cottom et al. (2023), Wang et al. (2021) (hereinafter Wang(b)), and Uniprot Accession No. C6XF68 (Uniprot Accession No. C6XF68, version 68, published online 02/22/2023). Applicant respectfully disagrees and asserts that the claimed invention is not obvious over the cited references. The Office Action acknowledges that Wang does not teach the limitations of claim 8 and cites Overly Cottom, Wang(b) and Uniprot Accession No. C6XF68 as teaching the sequences recited in claim 8. Applicant respectfully disagrees. The defects associated with the teachings of Wang and Eckert have been discussed above. The teachings of Overly Cottom, Wang(b) and the Uniprot Accession No. C6XF68 do not remedy these defects.
First, one skilled in the art would not have been motivated to combine the cited references with a reasonable expectation of arriving at the claimed peptide comprising a protein binding sequence that binds Candidatus Liberibacter spp. and an antimicrobial sequence, wherein the protein binding sequence is a sequence recited in claim 8 because only Wang teaches protein binding sequences that bind to a Candidatus Liberibacter protein. The teachings of Eckert, Overly Cottom, and Wang(b) are limited to non-Candidatus bacteria, e.g., E.coli. None of the cited references teach or suggest the applicability of their protein binding sequences to bind bacterial species undisclosed in their teachings, let alone Candidatus Liberibacter. Overly Cottom teaches that the p-barrel assembly machinery (a ~200 kDa multi-protein complex) is conserved among bacteria; however, Overly Cottom qualifies this teaching by adding that the p-barrel assembly machinery's overall composition can vary across bacterial species, and that a mutagenesis rate is observed between different bacterial species, e.g., in the p-barrel assembly machinery's component BamA. Overly Cottom concludes that more studies are needed to understand the structure and function of BAM across the spectrum of diverse bacteria (Overly Cottom, page 2, last paragraph). None of the references teach or suggest the protein binding sequences recited in claim 8 or linking these sequences to an antimicrobial peptide as required by claim 1, from which claim 8 depends. Furthermore, disclosure of longer amino acid sequences that contain a sequence recited in claim 8 would also not have motivated one skilled in the art to use the specific recited peptides (measuring between 12 and 31 amino acids) with a reasonable expectation of arriving at claim 8 in the absence of any teaching or suggestion that the shortened amino acid sequences could provide the function of binding to a surface protein on a cell of a plant pathogen, wherein the plant pathogen is a Candidatus Liberibacter spp. as required by the claims. No such teaching or suggestion is provided by the combined references or apparent from the general knowledge in the art.
Second, Overly Cottom's teaching that "there is promise for the development of broad spectrum novel antibiotics which can treat a wide range of bacterial infections," as cited by the Office Action, would also not have motivated one skilled in the art to prepare a peptide comprising an antimicrobial peptide and the specific separate protein-binding sequences of claim 8. Applicant further notes that the claimed combination peptide is undisclosed and not suggested by the combined cited references. Finally, the disclosure of darobactin by Wang and Overly Cottom would also not have motivated one skilled in the art to link darobactin to any other peptide sequence, let alone another protein binding sequence that binds Candidatus Liberibacter as required by the claims because both references teach that darobactin, itself, already provides binding and antimicrobial functionality and, thus, would not need any additional sequences performing any binding or antimicrobial activity. Moreover, the possibility of interfering with either one or both of darobactin's binding and/or antimicrobial functions by adding additional sequences would have further discouraged a skilled artisan from modifying the references' teachings. As noted above, even though all the individual pieces of the claimed invention may have been known separately in the prior art, and even though there was no evidence of undue technical hurdles or lack of a reasonable expectation of success, an invention may, nevertheless, be found non-obvious because no flaws or problems had been recognized which might prompt the modification necessary to arrive at the claimed invention. Therefore, one skilled in the art would not have been motivated to combine the references with a reasonable expectation of arriving at the claimed invention. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 103 is respectfully requested.
This argument has been fully considered and is found not persuasive for
the following reason(s):
These arguments are not persuasive in view of the modified rejection under 35 USC 103.
As described in the modified 103 rejection and previously herein, a OmpA sequence that was known to bind to BamA, which is highly conserved on all gram negative bacteria, was known and readily available, and has 100% sequence identity to instant SEQ ID NO: 14. It would have been obvious to modify the STAMP of Eckert to include the darobactin AMP of Wang (known as an affective AMP against various bacteria including CLas) and the known and readily available binding peptide of SEQ ID NO: 14 (taught to bind BamA which is conserved on bacteria including CLas) for the purpose of producing a STAMP that targets and has antimicrobial activity against CLas which is the causal bacteria of citrus greening/ HLB. There is reasonable expectation of success that the chimera peptide would be effective and bind CLas because Overly teaches BamA is highly conserved on all gram-negative bacteria, Wang(b) teaches a conserved “β signal” motif is located at the C terminus of the β barrel of many outer membrane proteins (OMPs) (abstract) allows for binding of OmpA to BamA (p. 2, ¶3- p. 3, ¶2, p. 12, discussion section), and Uniprot Accession No. C6XF68 teaches the known OmpA amino acid sequence that comprises a sequence with 100% sequence identity to instant SEQ ID NO: 14 and further specifically annotates (feature viewer) the sequence that makes up the C-terminus β-barrel, which is 100% identical to instant SEQ ID NO: 14. Because Wang(b) teaches this sequences binds to BamA which is conserved on all gram-negative bacteria (which includes CLas), one would have a reasonable expectation of success that this peptide sequence would bind BamA on CLas.
Applicant argues beginning on p. 10 of remarks dated 02/18/2026 the
following arguments:
Claim 9 is rejected under 35 U.S.C. § 103 as obvious over Wang (2021) as applied to claim 1 above, and further in view of Mirkov et al. (U.S. Patent No. 10,640,784), Eckert et al. (U.S. Patent No. 9,597,407), Overly Cottom et al. (2023), Wang et al. (2021) (hereinafter Wang(b)), and Uniprot Accession No. C6XF68 (Uniprot Accession No. C6XF68, version 68, published online 02/22/2023). Applicant respectfully disagrees and asserts that the claimed invention is not obvious over the cited references.
The Office Action alleges that claim 9 is obvious because Mirkov teaches an amino acid sequence that has an additional 8 amino acids at the N-terminal end and is, thus, allegedly a homolog of SEQ ID NO: 33. Applicant respectfully disagrees.
Even if one skilled in the art considered Mirkov's sequence together with the teachings of the other cited references, the skilled artisan would not have been motivated to combine Mirkov's sequence with any other peptide sequence taught in the other references to arrive at the specific peptides recited in claim 9. Initially, Applicant notes that SEQ ID NO: 33 is not recited in claim 9. Further, as explained above, one skilled in the art would not have been motivated to combine an antimicrobial sequence with any sequence disclosed by the combined cited references with a reasonable expectation of arriving at a peptide of claim 9 because Wang is the only reference teaching peptides able to bind to any Candidatus Liberibacter protein and, as explained above, Wang teaches one sequence that already performs both binding and antimicrobial activities, making any additional peptide at least redundant and potentially counterproductive in arriving at a peptide as claimed binding a Candidatus Liberibacter surface protein. Therefore, the claimed peptides are not obvious over the combined cited references. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 103 is respectfully requested.
This argument has been fully considered and is found not persuasive for
the following reason(s):
As described above and in the modified 103 rejection, Mirkov teaches a defensin peptide sequence (SEQ ID NO: 32 of Mirkov) comprising a sequence with 100% sequence identity to instant SEQ ID NO: 33 and has antimicrobial activity in citrus plants (claims 1 and 8 of Mirkov), specifically citrus Huanglongbing caused by Candidatus Liberibacter asiaticus (Col. 5, lines 44-67). The combination of the Amp taught by Mirkov (homolog of instant SEQ ID NO: 33), the linker taught by Eckert (instant SEQ ID NO: 34), and the β signal of OmpA (instant SEQ ID NO: 14) taught by Uniprot Accession No. C6XF68 would generate a homolog of instant SEQ ID NO: 27 and 28, depending the orientation of the linked sequences, thus producing these claimed sequence. In view of the prior art, it would be obvious to combine any AMP known or obvious to have AMP activity against CLas with a GGSGGS linker and the known peptide binding sequence taught to bind BamA of bacteria including CLas for the purpose of producing a STAMP that targets AMPs to BamA on CLas to inhibit Huanglongbing caused by Candidatus Liberibacter asiaticus (see 103 rejection(s) above).
Applicant argues beginning on p. 11 of remarks dated 02/18/2026 the
following arguments:
Claim 10 is rejected under 35 U.S.C. § 103 as obvious over Wang (2021) as applied to claim 1 above, and further in view of Overly Cottom et al. (2023). Applicant respectfully disagrees and asserts that the claimed invention is not obvious over the cited references.
The defects associated with the teachings of Wang and Overly Cottom have been discussed. A peptide as recited in claim 10, wherein the protein binding sequence binds to a BamA protein is not rendered obvious by Wang and Overly Cottom. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 103 is respectfully requested.
Claims 11-12 and 14-15 are rejected under 35 U.S.C. § 103 as obvious over Wang (2021) as applied to claim 1 above, and further in view of Sastoque Cala (U.S. Publication No. 2021/0144998). Applicant respectfully disagrees and asserts that the claimed invention is not obvious over the cited references.
The defects associated with the teachings of Wang have been discussed. Sastoque disclosing active agents of its compositions in Tables 1 and 2, where none of the disclosed agents is a peptide, let alone a peptide as recited in the claims does not cure the defects of Wang. Thus, the combined references do not render the claims obvious. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 103 is respectfully requested.
Claim 13 is rejected under 35 U.S.C. § 103 as obvious over Wang (2021) and Sastoque Cala (U.S. Publication No. 2021/0144998) as applied to claims 1, 11, and 12 above, and further in view of Schaefer (2023). Applicant respectfully disagrees and asserts that the claimed invention is not obvious over the cited references.
The defects associated with the teachings of Wang and Sastoque have been discussed. Schaefer disclosing uses of acetonitrile does not cure these defects. Thus, the combined references fail to render claim 13 obvious. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 103 is respectfully requested.
Claims 17-20 are rejected under 35 U.S.C. § 103 as obvious over Wang (2021) and Eckert et al. (U.S. Patent No. 9,597,407), as applied to claims 1 and 16 above, and further in view of Sastoque Cala (U.S. Publication No. 2021/0144998). Applicant respectfully disagrees and asserts that the claimed invention is not obvious over the cited references. The defects associated with the teachings of Wang, Eckert, and Sastoque have been discussed. The combined references fail to render claims 17-20 obvious. Accordingly, reconsideration and withdrawal of the rejection under 35 U.S.C. § 103 is respectfully requested.
This argument has been fully considered and is found not persuasive for
the following reason(s):
Applicant appears to essentially argue the references do not cure the previously argued deficiencies of pending claims 1, 3, 5, 7-9, and 16, thus claims 10-15 and 17-20 which also rely on these references are not obvious for the same reasons.
This is not persuasive because the claims do appear obvious in view of the prior cited prior art (see modified 103 rejection and response to arguments previously herein).
Conclusion and Inquiries
No claims are allowed.
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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JESSICA N. STOCKDALE
Examiner
Art Unit 1663
/JESSICA NICOLE STOCKDALE/Examiner, Art Unit 1663
/CHARLES LOGSDON/Primary Examiner, Art Unit 1662
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