DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/08/2026 has been entered.
Status of the claims
The amendments received on 04/08/2026 have been entered.
Claims 1, 5-7, 15-21 and 23-28 are pending and are examined in this Office Action.
Rejections that are withdrawn
Objection to claims has been withdrawn in light of applicant’s amendment of claim to remove superfluous citation of claim 6 and deletion to recite colon (:) in claims 1, 5-7, 15-21 and 23-28.
Claim Interpretation
In claim 1 line 1, recitation of phrase “antimicrobial peptide” is interpreted to include polypeptide as defined by Luo et al. (US Patent Application Pub. No.: US 2011/0078820 A1, Pub. Date: Mar. 31, 2011) as “they are short sequence peptides with generally fewer than 50 amino acid residues, which have antimicrobial activity against microorganisms.” (Luo, page 1, paragraph 0007).
In claim 1 line 1-2 recitation of phrase “effective against plant pathogens” is interpreted since applicant has not expressly defined the phrase, it is interpreted that the antimicrobial polypeptide would be effective if it would reduce any amount of pathogen population.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Following analysis has been modified since applicant has deleted SEQ ID NO:9 and recited SEQ ID NO:11 in claims 22, 24, 26 and 28.
Obvious over Kuhn et al. and further in view of Barry et al., Hopp et al. Prithviraj et al. and Jung et al.
Claims 1 and 23-28 are rejected under 35 U.S.C. 103 as being unpatentable over Kuhn et al. (Pub. No.: US 2020/0385429 A1, Pub. Date: Dec. 10, 2020), and further in view of Barry et al. (WIPO International Pub. Num.: WO 2017 /192560 A1, International Publication Date: 11/09/2017); and further in view of Prithviraj et al. (Published: 2005, Journal: The Plant Journal, Vol. 42, pages: 417-432); and further in view of Hopp et al. (US Patent No.: 4,554,101, Date of Patent: Nov. 19, 1985) and further in view of Jung et al. (Published: 2014, Journal: Plant Breed. Biotech., Vol. 2(1), pages:1-13).
Claims are drawn to a antimicrobial peptide as SEQ ID NO:11 effective against plant pathogens Botrytis cinera, Fusarium oxisporum etc.
Regarding claims 1 and 23-28, Kuhn et al. teaches antimicrobial peptides and methods of using them (Kuhn, page 1, paragraph 0001).
Kuhn et al. teaches an amino acid sequence they refer to as SEQ ID NO: 1 that matches 12 of the 17 amino acids from the instant SEQ ID NO: 11. The difference are 5 amino acids (see sequence alignment below).
Alignment of SEQ ID NO: 11 to Issued patents AA:
RESULT 9
US-16-769-025-1
Sequence 1, US/16769025
Patent No. 11352396
GENERAL INFORMATION
APPLICANT: ZOETIS SERVICES LLC
APPLICANT: ZOOK, Christopher A
APPLICANT: KUHN, Michael
APPLICANT: SHEEHAN, Derek J
APPLICANT: PHELPS, Hilary J
APPLICANT: BAIMA, Eric J
APPLICANT: EWIN, Richard A
TITLE OF INVENTION: ANTIMICROBIAL PEPTIDES AND METHOD OF USING SAME
FILE REFERENCE: ZP000218A
CURRENT APPLICATION NUMBER: US/16/769,025
CURRENT FILING DATE: 2020-06-02
PRIOR APPLICATION NUMBER: PCT/US2018/064029
PRIOR FILING DATE: 2018-12-05
PRIOR APPLICATION NUMBER: 62/595,725
PRIOR FILING DATE: 2017-12-07
NUMBER OF SEQ ID NOS: 117
SEQ ID NO 1
LENGTH: 18
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Antimicrobial peptide
Query Match 78.2%; Score 86; Length 18;
Best Local Similarity 70.6%;
Matches 12; Conservative 5; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KFCWRVCYRGICFKKCR 17
|:|:||||||||:::||
Db 1 KWCFRVCYRGICYRRCR 17
Kuhn et al.’s claim 22 teaches amino acid sequence comprises, at its N-terminus, Kuhn’s SEQ ID NO: 1 (KWCFRVCYRGICYRRCRD), or a peptide that differs from Kuhn’s SEQ ID NO: 1 by four amino acids, wherein the amino acids differing from the Kuhn’s amino acids of SEQ ID NO: 1 are independently selected from the group consisting of in second position phenyl alanine (F), in fourth position tryptophan (W), in 15th position lysine (K) (Kuhn, page 34, claim 22) (see snippet below). If one were to make these three substitutions that are expressly suggested by Kuhn et al., then one would arrive at a peptide that matches 15 of the 17 amino acids in the instant SEQ ID NO: 11 (see alignment above). Furthermore, Kuhn et al. teaches their sequence could be 17-22 amino acids long and comprising, at its N-terminus, SEQ ID NO:12 (X0X1X2CX3X4X5CX6X7X5X9CYX10X11 CX12X13) wherein the position X13 could be 0-4 amino acid long which lead to minimum of 17 amino acid long peptide sequence as taught by applicant (page1, paragraph 0005).
1 KFCWRVCYRGICFKKCR 17
||||||||||||::|||
1 KFCWRVCYRGICYRKCR 17
PNG
media_image1.png
884
1390
media_image1.png
Greyscale
Kuhn et al. teaches SEQ ID NO: 1 that has Tyrosine (Y) in 13th position and Arginine (R) in 14th position. Kuhn et al. further teaches the Lysine (K) of position 14 can differ by a histidine (H) of position 14 (Kuhn et al., page 34, claim 1).
Kuhn et al. teaches Antimicrobial Peptides (AMPs) are an essential component of the host defense system of organisms throughout nature and they offer protection from invading pathogen such as bacteria, fungi, parasites and viruses (Kuhn et al., page 1, paragraph 0004). Kuhn et al. teaches different peptides in Table 1 with different derivations from SEQ ID NO: 1, where they have showed the activity against microbes S. aureus and E. coli (Kuhn et al., page 6, paragraph 0075-0076, Table 1, Table 2).
Kuhn et al. however does not teach the remaining two amino acids out of 17 are phenyl alanine (F) in 13th position and Lysine (K) in 14th position.
However, a conservative substitution of Tyrosine (Y) to phenylanaline (F) and Arginine (R) to Lysine (K) of Kuhn et al. to synthesize a variant amino acid without changing its antimicrobial activity was known to the art. Barry et al. expressly teaches conservative amino acid substitutions may be made at one or more predicted nonessential amino acid residues without altering biological activity of the protein (Barry et al., page 14, lines 30-33). Barry et al. teaches a "conservative amino acid substitution" is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain and families of amino acid residues having similar side chains have been defined in the art wherein the families include: amino acids with basic side chains (e.g., lysine (K), arginine (R); aromatic sidechains (e.g., tyrosine(Y), phenylalanine(F)); large aromatic side chains (e.g., tyrosine, phenylalanine) (Barry et al., page 15, lines 1-13). Furthermore, Barry teaches substitution of like amino acids can be made effectively on the basis of hydrophilicity wherein the arginine (R) (+3.0); lysine (K) (+3.0); and tyrosine (Y) (-2.3); phenylalanine (F) (-2.5); have similar hydrophilicity values (Barry et al., page 16, lines 19-24). Barry et al. furthermore constructs different libraries of IPD090Aa variants of Barry’s SEQ ID NOs: 1 and 5 with overlapping homology (Barry et al., Page 131, Table 9) where there is substitution of Y to F in for example in SEQ ID NO: 281, and K to R (K336R) in SEAQ ID NO: 314 (Barry et al., page 136-139, Table 12). Hence someone skilled in art would substitute tyrosine (Y) and arginine (R) with phenylalanine (F) and lysine (K) respectively of Kuhn et al.’s SEQ ID NO: 1 that would lead to the SEQ ID NO: 11 of Applicant.
1 KFCWRVCYRGICFKKCR 17
|||||||||||||||||
1 KFCWRVCYRGICFKKCR 17
Furthermore, Hopp et al. claim 1 teaches a method of synthesizing a peptide comprising at least six amino acid residues of an antigenic (i.e. antimicrobial) determinant on an antigenic protein by determining hydrophilicity by repetitive local averages of hydrophilicity values wherein the arginine and lysine (with hydrophilicity of 3) and tyrosine and phenyl alanine (the hydrophilicity of -2.3 and -2.5, see Table below) that has similar hydrophilicity would have similar antimicrobial activity.
PNG
media_image2.png
427
506
media_image2.png
Greyscale
Prithviraj et al. further teaches S. aureus elicited typical bacterial disease symptoms in in vitro and soil-grown A. thaliana plants when the leaves were infiltrated or dip inoculated with bacterial cell suspensions, or when the roots of these plants were inoculated (Figure 1a–g) (page 418, right last paragraph) where in the bacterial population increased inside the infected leaf (syringe infiltrated) as evidenced by an increase in the colony-forming units (cfu) (Figure 1g) (page 419. Left paragraph 2). Prithviraj et al. teaches the growth bacterium was found in the wildtype Col-O leaves thus they are pathogenic to the wild type Col-O (see Figure 1g below). Prithviraj et al. teaches infected leaves turned chlorotic, resulting in the death of the leaf, spreading disease more rapidly to other part of plant compared to control plants with clear chlorotic and fasciation symptoms (Prithviraj et al., page 418 and 419, right last paragraph and left first paragraph). Thus S. aureus is pathogenic to Arabidopsis and hence it is a plant pathogen.
PNG
media_image3.png
887
1482
media_image3.png
Greyscale
Furthermore, Jung et al. teaches antimicrobial peptides (AMPs) show broad-spectrum antimicrobial activities against various microorganisms, including Gram-positive and Gram-negative bacteria, fungi, and viruses wherein most AMPs, with their amphipathic nature, directly act on the membrane of the pathogen (page 2, left paragraph 1). Jung et al. teaches AMPs are first line of defense in plants and animals, and resistance against them is much less observed compared with current antibiotics (page 2, left paragraph 1). Jung et al. teaches AMPs from various sources have been demonstrated to confer resistance against fungal and bacterial pathogens in an array of genetically engineered plant species, including Arabidopsis, tobacco, tomato etc. (page 2, left paragraph 1). Thus, there was reasonable expectation that AMPs had broad-spectrum antimicrobial activities that would also include antimicrobial against plant pathogen. Someone skilled in the art would test in other plant pathogens for effect of obvious sequence of SEQ ID NO: 11 with reasonable expectation of antimicrobial activity.
Furthermore, Jung et al. teaches the AMPs has been found effective against Botrytis cinerea in A. thaliana, Pseudomonas syringae in tobacco tomato, Erwinia spp. in potato, Fusarium oxysporum in tomato, melon, banana, tomato, tobacco, Brassica rapa (i.e. Canola) etc., Fusarium graminearum in maize, Rhizoctonia solani in maize (page 6 and 7, Table 2 and 3). Thus, some skilled in the art would test the obvious peptide of these plant pathogens with reasonable success of finding effective against the plant pathogen.
Kuhn et al., Hopp et al., Prithviraj et al. and Jung et al. does not teach the AMP as SEQ ID NO:11 is effective against for example R. solani , F. oxysporum at a concentration of 0.125 to 10 micromolar.
Noor et al. showed the method of testing different peptides for effectivity against Staphylococcus aureus using range of molarity from for example 0.01- 100 μM (see Figure 1 below).
The minimum Bactericidal (fungicidal) concentration which applicant describes as “value represents the lowest concentration that completely kills the population, resulting in no growth in the MBC plate (Spec, page 10, paragraph 0041) as also taught by Noor et al. for 0.01- 100 μM (see Figure 1 below) would have been empirically determined and is an optimization of process. According to section 2144.05 of the MPEP, “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”).
A particular parameter must first be recognized as a result-effective variable, i.e., a variable, which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation. In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977). Prior arts teach the AMP of SEQ ID NO: 11 that would be an effective antimicrobial peptide, therefore, determining the specific concentration of 0.125 to 10 μM to be effective against range of plant pathogens in claim 1 is a routine experimentation.
PNG
media_image4.png
764
1558
media_image4.png
Greyscale
Thus, the antimicrobial peptide would be effective against plant pathogens of Fusarium oxysporum and Pseudomonas syringae etc. as inherent property of an obvious antimicrobial peptide of SEQ ID NO: 11.
Furthermore, Jung et al. teaches antimicrobial peptides (AMPs) show broad-spectrum antimicrobial activities against various microorganisms, including Gram-positive and Gram-negative bacteria, fungi, and viruses wherein Most AMPs, with their amphipathic nature, directly act on the membrane of the pathogen (page 2, left paragraph 1). Jung teaches AMPs are first line of defense in plants and animals, and resistance against them is much less observed compared with current antibiotics (page 2, left paragraph 1). Jung teaches AMPs from various sources have been demonstrated to confer resistance against fungal and bacterial pathogens in an array of genetically engineered plant species, including Arabidopsis, tobacco, tomato etc. (page 2, left paragraph 1). Thus, there was reasonable expectation that AMPs had broad-spectrum antimicrobial activities that would also include antimicrobial against plant pathogen. Someone skilled in the art would test in plant pathogens for effect of obvious sequence of SEQ ID NO: 11 with reasonable expectation of antimicrobial activity against plant pathogen.
Kuhn et al. teaches their described antimicrobial peptides can be used for the treatment of prevention (i.e., effective against) of infectious disorders caused by Pseudomonas species (Kuhn et al., page 5, paragraph 0070). Furthermore, the antimicrobial peptide would be effective against plant pathogens of Pseudomonas sp., Xanthomonas sp. etc. as inherent property of an obvious antimicrobial peptide of SEQ ID NO: 11.
Thus it would have been obvious to one skilled in the art to apply a known technique of conservative amino acid substitution taught by Barry et al. and Hopp et al. to the antimicrobial polypeptide with amino acid sequence of SEQ ID NO: 1 taught by Kuhn et al. to change the arginine (R) to lysine (K) in position 14th; and tyrosine (Y) to phenylalanine (F) in position 13th of the Kuhn’s amino acid sequence of SEQ ID NO: 1 that has similar side chains and similar hydrophilicity index, with a reasonable expectation of success of producing a variant of SEQ ID NO:1 that has similar antimicrobial biological activity of SEQ ID NO: 1 as antimicrobial polypeptide against a plant pathogen S. aureus as taught by Kuhn et al. Furthermore, it would have been obvious to test in a plant pathogen taught by Jung et al.
Furthermore, the peptide would have been effective against the pathogen at a concentration of 0.125 to 10 micromolar as inherent property of the Kuhn’s taught peptide.
Thus, it would have been obvious to a skilled in the art to try choosing from finite number of identified peptides suggested by Kuhn et al. and their modification further in view of Barry et al., Hopp et al., Prithviraj et al., and Jung et al. and test the peptide as described by Noor et al. including plant pathogen with reasonable expectation of success in obtaining SEQ ID NO:11 which would have been effective against a plant pathogens for example for F. oxysporum and P. syringae etc. Furthermore, the effectivity at concentration of 0.125 to 10 micromolar would have been found as inherent property of the obvious sequence taught by Kuhn et al. and further in view of Barry et al. and Hopp et al.
Obvious over Kuhn et al. and further in view of Barry et al., Hopp et al., Jung et al., Noor et al. and Luo et al.
Claims 1, 5-7, 16-19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kuhn et al. and further in view of Barry et al., and further in view of Hopp et al. and further in view of Noor et al.; and further in view of Jung et al.; and further in view of Luo et al. (US Patent Application Pub. No.: US 2011/0078820 A1, Pub. Date: Mar. 31, 2011).
Claims are drawn to a antimicrobial peptide as SEQ ID NO:11 effective against plant pathogens Botrytis cinera, Fusarium oxisporum etc. The claims are further drawn to an expression vector and a host cell and transgenic plant comprising the expression vector.
Regarding claim 1, Kuhn et al. and further in view of Barry et al., Hopp et al., Noor et al. and Jung et al. teach the Applicant’s SEQ ID NO: 11 that would be effective against a plant pathogen, see analysis above.
Regarding 5, Luo et al. teaches two constructs of AMP genes Pen4-1 and Ib-AMP4 in fighting against disease (Lou et al., page 17, paragraph 0179).
Regarding claims 6, 7, 16, 17, Luo et al. teaches designing and synthesizing two pSB 11-based Agrobacterium (i.e. host) binary vectors for creeping bent grass transformation with the chimeric gene constructions consisting of antimicrobial peptide gene Pen4-1 or Ib-AMP4 or the combination of the two antimicrobial peptide genes under the control of maize ubiquitin promoter, a bar gene under the control of rice ubiquitin promoter and a RNAi construction using the creeping bent grass FLO/LFY homolog that regulates the vegetative to reproductive developmental transition of meristems under the control of a CaMV 35S promoter (Lou, page 14, paragraph 0152).
Regarding claims 17-19, 21, Luo et al. teaches twenty five transgenic turfgrass lines constitutively expressing the Pen4-1 gene and five transgenic lines expressing the AP24::Pen4-1 fused gene were produced and all of them showed normal morphology and were fertile and the results showed that the Pen4-1 gene was efficiently expressed (Lou, page 22, paragraph 0229). Furthermore, producing seeds from a fertile plant is known in the art.
Obvious over Kuhn et al. and further in view of Barry et al., Hopp et al., Jung et al., Noor et al., and Kazan et al.
Claims 1, 5, 16, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Kuhn et al. and further in view of Barry et al. and further in view of Hopp et al. and further in view of Noor et al.; and further in view of Jung et al.; and further in view of Kazan et al. (Published Year: 2002, Journal: Molecular Breeding, Vol.: 10, pages 63-70).
Claims are drawn to a antimicrobial peptide as SEQ ID NO:11 effective against plant pathogens. The claims are further drawn to an expression vector and a host cell and transgenic canola plant comprising the expression vector.
Regarding claim 1, Kuhn et al. and further in view of Barry et al., Hopp et al., Noor et al. and Jung et al. teach the Applicant’s SEQ ID NO: 11 that would be effective against a plant pathogens recited in claim 1, see analysis above.
Regarding claims 5, 16, and 19-20, Kazan et al. teaches antimicrobial peptide MiAMP1 when transformed with 35S-MiAMP1 construct to a canola plant increases disease resistance to Leptosphaeria maculans (causal agent of blackleg disease) (Kazan et al., page 63, Abstract).
Thus, someone skilled in art would develop an expression construct for a microbial peptide to transform a Canola plant as taught by Kazan et al. and would replace and replace it with the peptide taught by Kuhn et al. and further in view of Barry et al., Hopp et al. that would include all the amino acid sequence of Applicant’s SEQ ID NO: 11 to develop a construct and transgenic Canola plant comprising Applicant’s SEQ ID NO:11. Thus the peptide produced upon expression would be effective against plant pathogen of Canola.
Response to Argument for Rejection
Applicant's arguments 04/08/2026 have been fully considered but they are not persuasive.
Since applicant has cancelled the recitation of SEQ ID NO:9, the arguments regarding SEQ ID NO:9 are moot point.
Applicant argues Kuhn, Barry, Prithviraj and Jung fail to disclose the claimed peptide at the claimed concentrations with a reasonable expectation of success for antimicrobial activity against plant pathogens Botrytis cinera, Clavibaceter michiganensis, Colletotrichum coccodes, Pseudomonas syringae, Erwinia catatovora, Xanthomas sacchari, Rhizoctonia solani, Verticillium dahlia, Didymella bryoniea, or Fusarium oxysporum (Response to Rejection, page 7, paragraph 3).
Applicant argues the Advisori Action ignores the evidence in the Declaration of Dr. Jaynes, which applies, mutatis mutandis, to the arguments made in the Current Action. Applicant argues the evidence on the record is that a change, addition, or subtraction of a single amino acid (a structural change) can significantly change the activity of a peptide (a functional change). Applicant argues the current Action admits that Kuhn fails to teach SEQ ID NO: 11. Applicant argues thus the art of Kuhn is no longer applicable to the claims as amended because the art cited, alone or in combination, must match the peptide sequence exactly or the art is inapplicable (Response to Rejection, page 7, paragraph 4).
Applicant argues Without demur, the peptides must also have a reasonable expectation of having an effect on the specific plant pathogens claimed, viz., Botrytis cinera, Clavibaceter michiganensis, Colletotrichum coccodes, Pseudomonas syringae, Erwinia catatovora, Xanthomas sacchari, Rhizoctonia solani, Verticillium dahlia, Didymella bryoniea, or Fusarium oxysporum, with a reasonable expectation of success. Applicant argues those teachings are found solely in the present specification. Applicant argues the use of the close-ended transition phrase "consisting of' means that the claims, as amended, avoid the art of Kuhn, as the art of Kuhn only teaches 18-mers or longer. Applicant argues the advisory action admits that "Kuhn et al. teaches amino acid sequence that is 18-21 amino acids long", not shorter peptides. Applicant argues therefore, the other art cited must specifically modify this specific peptide, not a general peptide, to be able to provide that reasonable expectation of success. Applicant argue nothing in Barry, Prithviraj and Jung teaches the specific changes that are required to make the peptide active against Botrytis cinera, Clavibaceter michiganensis, Colletotrichum coccodes, Pseudomonas syringae, Erwinia catatovora, Xanthomas sacchari, Rhizoctonia solani, Verticillium dahlia, Didymella bryoniea, or Fusarium oxysporum. Applicant argues the office must provide the specific motivation for the changes because the evidence on the record, the Declaration of Dr. Jaynes rebuts the position in the Current Action that this is routine experimentation (Response to Rejection, page 7, paragraph 5).
Applicant argues as explained by Dr. Jaynes in his Declaration, pointing to evidence of record in this case (Jung), a single amino acid substitution, addition, or deletion leads to a completely different activity for the peptide, its concentration, or its antimicrobial activity. Applicant argues even well-known conservative substitutions cannot meet the reasonable expectation of success standard given the uncertainty inherent in making even a single amino acid substitution and/or changing the length of a peptide, as these affect their binding to active sites, binding sites, hydrophilicity, and binding constant, to name a few. Applicant argues while Barry may include some teachings related to peptide substitution, again, use of the close-ended language "consisting of' eliminates variability from the peptide sequence and renders the rejection inoperative. Applicant argues at best, the Office finds in the art an invitation to experiment without any reasonable expectation of success (Response to Rejection, page 7 and 8, last and first paragraphs).
Applicant argues nothing in the combination of Kuhn and Prithviraj teaches that the peptide, as claimed, has any antimicrobial activity against plant pathogens Botrytis cinera, Clavibaceter michiganensis, Colletotrichum coccodes, Pseudomonas syringae, Erwinia catatovora, Xanthomas sacchari, Rhizoctonia solani, Verticillium dahlia, Didymella bryoniea, or Fusarium oxysporum, wherein the plants affected include maize, soybean, sunflower, sorghum, canola, wheat, alfalfa, cotton, rice, barley, or millet. Applicant argues Prithviraj teaches activity against Staph. aureus, which is not one of the plant pathogens claimed. As such, for at least these reasons, the prima facie case of obviousness fails (Response to Rejection, page 7 and 8, last and first paragraphs).
Applicant’s arguments are fully considered but they are not persuasive since:
Regarding argument on “consisting” would mean exact length, the length was expressly taught by Kuhn et al. and further in view of Barry et al. which expressly teaches the modification leading to SEQ ID NO: 11, see analysis above.
Kuhn et al. teaches amino acid sequence that is 17-22 amino acids long (page1, paragraph 0005) and comprises, at its N-terminus, Kuhn’s SEQ ID NO: 1 (KWCFRVCYRGICYRRCRD), or a peptide that differs from Kuhn’s SEQ ID NO: 1 by four amino acids, wherein the amino acids differing from the Kuhn’s amino acids of SEQ ID NO: 1 are independently selected from the group consisting of in second position phenyl alanine (F), in fourth position tryptophan (W), in 15th position lysine (K) (Kuhn, page 34, claim 1). If one were to make these three substitutions that are expressly suggested by Kuhn et al., then one would arrive at a peptide that matches 15 of the 17 amino acids in the instant SEQ ID NO: 11. Furthermore all 2 different amino acid differences are conservative changes (see alignment above). Kuhn further teaches a generic polypeptide with an amino acid sequence that is 17-22 amino acids long (page 2, paragraph 0028).
Regarding argument on the Declaration of Dr. Jaynes showed that the single amino acid (a structural change) can significantly change the activity of a peptide ( a functional change) was not found persuasive since a lysine (K) rich protein would increase the antimicrobial activities for example the use of Lysine rich AMPs were also described in Jung et al. page 3. Furthermore, Declaration of Dr. Jaynes argues about the Fujii et al. art which was used to rejection when applicant recited SEQ ID NO: 9 which has been deleted in instant amendment therefore most of the arguments in the declaration are moot point.
Regarding the argument on "Kuhn et al. teaches amino acid sequence that is 18-21 amino acids long", not shorter peptides was not found persuasive since for example claim 30 teaches the peptide would differ from SEQ ID NO:1 by three, two or one amino acids. Furthermore, Kuhn et al. showed the AMP of size 17 amino acid long for example SEQ ID NOs: 23-27, 30, 34-38, 40-64 etc. Kuhn et al. teach that their peptides are 17-22 amino acid long wherein the position X13 would be 0-4 amin acid long polypeptide showing amino acid in position X13 could be absent leading to only 17 amino acid long sequence (page1, paragraph 0005).
Barry et al. expressly teaches conservative amino acid substitutions may be made at one or more predicted nonessential amino acid residues without altering biological activity of the protein (Barry, page 14, lines 30-33). Thus, Kuhn and further in view of Barry has expressly taught to produce the Applicant’s SEQ ID NO: 11, which would have antimicrobial activity.
Regarding the argument on peptide either matches the peptide sequence claimed or it doesn't was not found persuasive since there is extensive teachings in Kuhn to at a peptide that matches 15 of the 17 amino acids in the instant SEQ ID NO: 11. Furthermore all 2 different amino acid differences are conservative changes (see alignment above). Testing and finding effectiveness of such changes are within the skill of the art as taught by Barry et al.
Regarding argument on applicant’s finding of the protein is effective against specific bacteria and fungi recited in claim 28, Kuhn et al. teaches their derivatives of SEQ ID NO: 1 has antimicrobial activity to S. aureus (Kuhn, page 7, paragraph 0079). Prithviraj further teaches S. aureus elicited typical bacterial disease symptoms in in vitro and soil-grown A. thaliana plants and, Jung teaches antimicrobial peptides (AMPs) show broad-spectrum antimicrobial activities against various microorganisms. Thus someone skilled in art would have reasonable expectation of the obvious SEQ ID NO: 11 to be antimicrobial to a plant pathogen. Furthermore, it would have been obvious to test in a plant pathogen taught by Jung for example for Pseudomonas syringae or Fusarium oxysporum etc. Furthermore, the effectivity to the pathogens are inherent property of the expressly taught AMPs which was also suggested by Jung et al.
Furthermore, with the teaching of Kuhn et al.’s 15 of 17 amino acids and teaching of conservative substitution of Barry there would be very few combinations to try to come to the invention of SEQ ID NO: 11, see analysis above. Jung teaches the broad-spectrum antimicrobial activities against various microorganisms, hence someone skilled in the art would test the activities to other plant pathogen that would lead to the invention to find the SEQ ID NO: 11 would be effective against the other plant pathogen other than S. aureus as recited in claim 28, see analysis above.
Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. “[T]he test for obviousness is what the combined teachings of the references would have suggested to a person having ordinary skill in the art (PHOSITA).”
Conclusion
No claim is allowed.
Examiner’s Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SANTOSH SHARMA whose telephone number is (571)272-8440. The examiner can normally be reached Mon-Fri 8:00 AM - 5:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, AMJAD A. ABRAHAM can be reached at (571)270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SANTOSH SHARMA/Examiner, Art Unit 1663
/DAVID H KRUSE/Primary Examiner, Art Unit 1663
Prosecution Insights