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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 March 12, 2025 has been entered.
Status of the Claims
Claims 1-16 were originally filed August 26, 2021.
The amendment received October 25, 2022 added status identifiers only.
The amendment received March 17, 2023 amended claims 1 and 5-8, canceled claims 2-4, and added new claims 17 and 18.
The amendment received September 21, 2023 amended claims 1, 5, and 7.
The amendment received July 16, 2024 amended claim 1.
The amendment received March 12, 2025 amended claims 1 and 7 and added new claim 19.
Claims 1 and 5-19 are currently pending.
Claims 1, 5, 7, and 19 are currently under consideration.
Election/Restrictions
Applicants elected, without traverse, Group I (claims 1-8) in the reply filed on October 25, 2022. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 9-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected methods, there being no allowable generic or linking claim.
Applicants elected, without traverse, GGH (SEQ ID NO: 31) and SM15 (SEQ ID NO: 11) as the species in the reply filed on October 25, 2022. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 6, 8, 17, and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Priority
The present application claims the benefit of 63/070,644 filed August 26, 2020.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
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.
Claim 19 is 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 new matter rejection.
In the response received March 12, 2025, applicants’ representative stated that “The amendments and new claim are fully supported by the present application as filed. No new matter has been added.”. This is NOT sufficient to provide support in the originally filed specification. Applicants’ representative should go line by line and/or limitation by limitation in the claim and provide page and line numbers from the original specification as to where support can be found.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 19 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the presently claimed antimicrobial peptide. For example, it is unclear if the various bacteria recited in the claim are required as a composition or not. It also appears that the bacteria may simply be part of an intended use for the antimicrobial peptide and do not provide any additional structure or components for the antimicrobial peptide.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 19 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 19 is dependent on independent claim 1. Independent claim 1 requires fusion polypeptides of SEQ ID NO: 31-SEQ ID NO: 11; SEQ ID NO: 31-SEQ ID NO: 15; SEQ ID NO: 31-SEQ ID NO: 16; SEQ ID NO: 32-SEQ ID NO: 11; SEQ ID NO: 32-SEQ ID NO: 15; SEQ ID NO: 32-SEQ ID NO: 16. Dependent claim 19 reiterates the structure recited in claim 1 and simply adds functional language that does not alter the structure. Therefore, the functional language of claim 19 does not alter the structure of independent claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Maintained and/or Modified* Rejection
*wherein the modification is due to amendment
Claim Rejections - 35 USC § 112
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, 7, and 19 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 new matter rejection.
Support in the original specification was not found for “and wherein the antimicrobial peptide displays higher antimicrobial activity than the peptide portion alone” for the genus of SEQ ID NOs: 11, 15, or 16 conjugated to any one of SEQ ID NOs: 31 or 32.
It is also respectfully noted that “antimicrobial” (e.g. bacteria, virus, fungus, etc.) is much broader in scope than the bacteria utilized in the specification.
In addition, it is applicants’ responsibility to specifically point out support in the originally filed specification (i.e. via page and line numbers and/or paragraph number) for any claim amendments. In the response received July 16, 2024, applicants simply pointed to the entire specification (see page 4, first full paragraph).
In the examples, only SEQ ID NO: 31-SEQ ID NO: 11 (GGH-CM15) and SEQ ID NO: 32-SEQ ID NO: 11 (VIH-CM15) fusions were tested for antimicrobial activity (i.e. of the claimed fusion polypeptides). See Table 2. For E. coli (ATCC 25922) and E. coli (KpC + 1812446), there was no difference between CM15 alone and GGH-CM15. For E. coli (KpC + 1812446) and P. aeruginosa (ATCC 27853), VIH-CM15 has less antimicrobial activity than CM15 alone.
Paragraph 51 of the original specification reads: [0051] These data indicate that, for some bacterial strains, the antimicrobial activity of CM15 was modulated by incorporation of the ATCUN motif: the potency of the GGH and VIH variants of CM15 against carbapenem-resistant K. pneumoniae (KpC+ 1825971), for example, was 4-fold and 8-fold higher, respectively, than the potency of the original peptide. The antibacterial activity of CM15 against the carbapenem-resistant strains E. coli (KpC +1812446), E. coli (KpC +2101123), E. coli (ATCC 25922), and P. aeruginosa (ATCC27853) was marginally improved by the presence of the ATCUN motif (Tables 3 and 4).
Paragraph 51 continued (i.e. after Tables 3 and 4): This small improvement is nevertheless significant considering that pulmonary infections caused by carbapenem-resistant K. pneumoniae (KpC+ 1825971) have a mortality rate on the order of 40%67. However, ATCUN modification lowered the antimicrobial activity of citropini.1, resulting in as much as a 3-fold decrease in antimicrobial activity against the Gram-negative and Gram-positive bacteria tested (Table 2). As ATCUN motifs require Cu(II) ions for their catalytic activity, we supplemented the growth medium with 0.25 pM Cu(II) solution. Antimicrobial activities obtained after the addition of Cu(II) ions were not changed when compared to those assayed in MH broth only (Table 2). The lack of enhanced activity upon the addition of Cu(II) underscores the ability of ATCUN-AMPs to scavenge labile Cu(II) ions from the media or the bacteria themselves64.
Table 3 shows less antimicrobial activity with GGH-CM15 compared to CM15 alone for E. coli (KpC +1812446).
In addition, it is respectfully noted that many results comparing CM15 alone with GGH-CM15 or VIH-CM15 provide a minimal improvement (see Tables 2-4; e.g. 2 mM verses 1 mM; 5 mM verses 4mM; etc.). Furthermore, it is unclear how the > results have been interpreted. Typically when showing > results for MIC, this is an upper limit for the assay. Thus, the > numbers are all the same. In Tables 2-4, the > numbers are all different. Therefore, it is unclear if there is actually a difference or not (i.e. maximum limit for assay has been reached and therefore one cannot differentiate between the results).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112, first paragraph (new matter), for claims 1, 5, 7, and 19 were considered but are not persuasive for the following reasons.
Applicants contend that “the evidence of record demonstrates that the recited combinations of peptide portions + amino-terminal Cu(II) and Ni(II) (“ATCUN”) binding motifs display higher antimicrobial activity than their corresponding peptide portions in the absence of the specified ACTUN binding motifs”.
Applicants’ arguments are not convincing since the data from the originally filed specification provided in the rejection above prove otherwise. It is also respectfully noted that “antimicrobial” (e.g. bacteria, virus, fungus, etc.) is much broader in scope than the specific bacteria species utilized in the originally filed specification. The results in the originally filed specification are exceedingly variable with regard to which bacterial strain is tested. See Figures 3A, 3B, and 4A-4C and Tables 2-8.
Maintained Rejection
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.
Claims 1, 5, 7, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Gonzalez et al., 2018, N-terminal Cu Binding Motifs Xxx-Zzz-His (ATCUN) and Xxx-His and their derivatives: Chemistry, Biology and medicinal Applications, Chemistry, 24(32): 8029-8041 and Eckert et al. U.S. Patent Application Publication 2017/0266306 published September 21, 2017.
For present claims 1, 7, and 19, Gonzalez et al. teach ACTUN motifs including GHH (present SEQ ID NO: 31) which may be fused to the N-terminus of antimicrobial peptides to increase activity (please refer to the entire reference particularly the abstract; sections 2.1, 5.1.1, 5.1.3, 5.2; Conclusions; Outlook).
However, while Gonzalez et al. teach the genus of antimicrobial peptides, Gonzalez et al. do not specifically teach the species of SEQ ID NO: 11 as the antimicrobial peptide.
For present claims 1, 5, and 19, Eckert et al. teach fusion polypeptides comprising CM15 – KWKLFKKIGAVLKVL (i.e. present SEQ ID NO: 11) at the C-terminus (please refer to the entire specification particularly the abstract; paragraphs 3, 7-13, 15, 17, 21, 22, 27, 28, 39, 77, 89, 93, 97-102, 107-114, 116-120, 222-224; Table 14).
The claims would have been obvious because the substitution of one known element (i.e. genus of antimicrobial peptide) for another (i.e. species of KWKLFKKIGAVLKVL) would have yielded predictable results (i.e. antimicrobial fusion with an ATCUN motif) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. making fusion polypeptides with antimicrobial peptides and ATCUN motifs) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. See KSR International Co. Teleflex Inc., 82 USPQ 2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Gonzalez et al. and Eckert et al. for claims 1, 5, 7, and 19 were considered but are not persuasive for the following reasons.
Applicants contend that there is no reasonable expectation of success in combining the ATCUN motif of Gonzalez et al. with the specific antimicrobial peptides of Eckert et al. and that one of skill in the art would be motivated to combine the references.
In the Declaration under 37 CFR 1.132 by Dr. Marcelo Der Torossian Torres provided September, 21, 2023, Dr. Marcelo Der Torossian Torres states that “whether or not the modification of a particular peptide with an ATCUN motif would result in a new species that actually possesses antimicrobial properties cannot be predicted in advance, and must be verified using experimental evaluation” (e.g. no reasonable expectation of success) and antimicrobial activity could be altered 2-4 fold (increase or decrease) based on mutations, addition of an ATCUN motif, or based on the type of bacteria (e.g. no reasonable expectation of success).
Applicants’ arguments are not convincing since the teachings of Gonzalez et al. and Eckert et al. render the fusion polypeptide of the instant claims prima facie obvious.
Gonzalez et al. teach ACTUN motifs including GHH (present SEQ ID NO: 31) which may be fused to the N-terminus of antimicrobial peptides to increase activity (please refer to the entire reference particularly the abstract; sections 2.1, 5.1.1, 5.1.3, 5.2; Conclusions; Outlook). Goncalez et al. teach that “Copper has been long known for its antimicrobial activity”, “a few cases of an increase in activity of AMPs with a native XZH motif (such as hecidin or ixosin[88]) by addition of CuII have been reported toward several microorganisms”, and “N-terminal elongation by XZH of the AMP anoploin, pro-apoptotic peptide, and sh-buforin showed about a 2-8 fold increase in activity” (see section 5.2). Thus, Gonzalez et al. teach that ACTUN-antimicrobial peptide fusions are possible and retain or even improve function.
Eckert et al. teach fusion polypeptides comprising CM15 – KWKLFKKIGAVLKVL (i.e. present SEQ ID NO: 11) at the C-terminus (please refer to the entire specification particularly the abstract; paragraphs 3, 7-13, 15, 17, 21, 22, 27, 28, 39, 77, 89, 93, 97-102, 107-114, 116-120, 222-224; Table 14). Thus, Eckert et al. teach that fusion polypeptides comprising CM15 – KWKLFKKIGAVLKVL (i.e. present SEQ ID NO: 11) at the C-terminus are possible. In addition, making fusion polypeptides which are functional is a well-known and a routine concept in the prior art. If functionality is an issue, several ways to resolve the issue are known in the art (e.g. utilizing flexible linkers, etc.; references will be provided upon request).
It is also respectfully noted that the present claims are drawn to a product, thus the product must simply exist (e.g. function in the preamble does not “breath life” into the body of the claim).
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999); Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81; and STX LLC. v. Brine, 211 F.3d 588, 591, 54 USPQ2d 1347, 1350 (Fed. Cir. 2000).
The wherein clause does not alter the structures claimed in independent claim 1. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) "adapted to" or "adapted for" clauses;
(B) “wherein” clauses; and
(C) "whereby" clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). The claims require specific structure (i.e. SEQ ID NOs: 11, 15, or 16 fused to any one of SEQ ID NOs: 31-59). Thus, the wherein clause does not appear to alter the function of the structures as claimed (although specific data for each fusion polypeptide is not provided in the present application).
Conclusive proof of efficacy is not required to show a reasonable expectation of success. See OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) which held that "To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"). See Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) which held that "This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness.". Also see Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); and Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) reasoning that "the expectation of success need only be reasonable, not absolute".
It is well-known in the prior art that different antimicrobial peptides have greater activity against some bacteria over others. Screening assays are also exceedingly common. This is supported by the originally filed specification (see Figures 3A, 3B, and 4A-4C and Tables 2-8) wherein the antimicrobial peptides alone and the fusion polypeptides have varying antibacterial activity depending on which bacteria species is tested (i.e. only specific bacterial species were tested, not the genus of microbes). In addition, the fusion polypeptides were sometimes better than the peptide alone, sometimes worse, and sometimes equal (see Figures 3A, 3B, and 4A-4C and Tables 2-8 and the rejection above).
Applicants may not pick and choose which data is better and then make broad generalizations regarding antimicrobial activity.
In the examples, only SEQ ID NO: 31-SEQ ID NO: 11 (GGH-CM15) and SEQ ID NO: 32-SEQ ID NO: 11 (VIH-CM15) fusions were tested for antimicrobial activity (i.e. of the claimed fusion polypeptides). See Table 2. For E. coli (ATCC 25922) and E. coli (KpC + 1812446), there was no difference between CM15 alone and GGH-CM15. For E. coli (KpC + 1812446) and P. aeruginosa (ATCC 27853), VIH-CM15 has less antimicrobial activity than CM15 alone.
Paragraph 51 of the original specification reads: [0051] These data indicate that, for some bacterial strains, the antimicrobial activity of CM15 was modulated by incorporation of the ATCUN motif: the potency of the GGH and VIH variants of CM15 against carbapenem-resistant K. pneumoniae (KpC+ 1825971), for example, was 4-fold and 8-fold higher, respectively, than the potency of the original peptide. The antibacterial activity of CM15 against the carbapenem-resistant strains E. coli (KpC +1812446), E. coli (KpC +2101123), E. coli (ATCC 25922), and P. aeruginosa (ATCC27853) was marginally improved by the presence of the ATCUN motif (Tables 3 and 4).
Paragraph 51 continued (i.e. after Tables 3 and 4): This small improvement is nevertheless significant considering that pulmonary infections caused by carbapenem-resistant K. pneumoniae (KpC+ 1825971) have a mortality rate on the order of 40%67. However, ATCUN modification lowered the antimicrobial activity of citropini.1, resulting in as much as a 3-fold decrease in antimicrobial activity against the Gram-negative and Gram-positive bacteria tested (Table 2). As ATCUN motifs require Cu(II) ions for their catalytic activity, we supplemented the growth medium with 0.25 pM Cu(II) solution. Antimicrobial activities obtained after the addition of Cu(II) ions were not changed when compared to those assayed in MH broth only (Table 2). The lack of enhanced activity upon the addition of Cu(II) underscores the ability of ATCUN-AMPs to scavenge labile Cu(II) ions from the media or the bacteria themselves64.
Table 3 shows less antimicrobial activity with GGH-CM15 compared to CM15 alone for E. coli (KpC +1812446).
In addition, it is respectfully noted that many results comparing CM15 alone with GGH-CM15 or VIH-CM15 provide a minimal improvement (see Tables 2-4; e.g. 2 mM verses 1 mM; 5 mM verses 4mM; etc.). Furthermore, it is unclear how the > results have been interpreted. Typically when showing > results for MIC, this is an upper limit for the assay. Thus, the > numbers are all the same. In Tables 2-4, the > numbers are all different. Therefore, it is unclear if there is actually a difference or not (i.e. maximum limit for assay has been reached and therefore one cannot differentiate between the results).
Regarding the conclusionary statements by Dr. Marcelo Der Torossian Torres (i.e. see below – this is the section that is considered “conclusionary”, not any section discussing data), no data was provided, thus it cannot be determined if the fusion polypeptide(s) still retain antimicrobial activity or not (e.g. a decrease does not necessarily correlate to no antimicrobial activity).
Dr. Marcelo Der Torossian Torres states that “whether or not the modification of a particular peptide with an ATCUN motif would result in a new species that actually possesses antimicrobial properties cannot be predicted in advance, and must be verified using experimental evaluation” (e.g. no reasonable expectation of success) and antimicrobial activity could be altered 2-4 fold (increase or decrease) based on mutations, addition of an ATCUN motif, or based on the type of bacteria (e.g. no reasonable expectation of success).
Dr. Marcelo Der Torossian Torres did refer to paragraph 51 of the present specification. In addition, in Figures 3B, 4A, 4B, and 4C and Tables 2-4 antimicrobial activity for GGH-CM15, VIH-CM15, GGH-Cit1.1, and VIH Cit1.1 are shown. While higher dosages are required in some instances for some bacteria, it does appear that some level of antimicrobial activity is present for the fusion polypeptides tested including Cit1.1 fused to either GGH or VIH (see Table 2).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. See In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition cannot have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Therefore, the fusion of SEQ ID NO: 31 to SEQ ID NO: 11 would have the same function as the presently claimed product of the same seqeucne.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the claims would have been obvious because the substitution of one known element (i.e. genus of antimicrobial peptide) for another (i.e. species of KWKLFKKIGAVLKVL) would have yielded predictable results (i.e. antimicrobial fusion with an ATCUN motif) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. making fusion polypeptides with antimicrobial peptides and ATCUN motifs) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. See KSR International Co. Teleflex Inc., 82 USPQ 2d 1385 (U.S. 2007).
Any discussion of unexpected results must be commensurate in scope with the present claims. It is respectfully noted that the present claims are drawn to a product. The “unexpected” results cited by applicant refer to 2 of the 6 different possible fusion polypeptides with varying results based on which bacterial strain is utilized.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
U.S. Patent Application Publications 2017/0224760 and 2012/0289454 regarding GGH (SEQ ID NO: 31).
Melino et al., 2014, Histatins: salivary peptides with copper(II)- and zinc(II)-binding motifs, The FEBS Journal, 281: 657-672 regarding histatins comprising N-terminal ATCUN or Cu(II) and Ni(II) binding motifs and a peptide portion with antimicrobial activity wherein the N-terminal ATCUN or Cu(II) and Ni(II) binding motifs include DXH and specifically DSH which encompasses present SEQ ID NOs: 41 (DYH), 43 (DHH), 50 (DSH), and 51 (DTH).
Future Communications
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER D STEELE whose telephone number is (571)272-5538. The examiner can normally be reached M-F 8-5.
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/AMBER D STEELE/Primary Examiner, Art Unit 1658