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 .
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located on at least pages 4, 5, 21-26, 32, 45-47, and 81.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1, 3-4, 7-11, 15, 20, 32, 36, 50, 54-57, 62, 65-67, and 69-70) and the species of an amount effective to treat Candidiasis including Candida biofilm (what is treated), Candida albicans (target fungal organism), integumental tissue (tissue), topical administration (route of administration), a peptide of SEQ ID NO: 2 (folding group), no functional group (functional group), and administering a buffer comprising 1 mM to 150 mM BTP (buffer) in the reply filed on 01/28/2026 is acknowledged. The traversal is on the grounds that US 20150366193, hereinafter Bevilacqua et al., does not teach or render obvious a shared special technical feature between the groups of inventions because they “fail to disclose a peptide having charged amino acid residues and hydrophobic amino acid residues arranged in a substantially alternating pattern.” This is not found persuasive because Bevilacqua et al. does disclose that the charged and hydrophilic residues alternate within the synthetic copolypeptide structures (see [0075]). Specifically, they teach structures like poly(L-lysine-HCl)55-block-poly(racemic-hydrophobic amino acid)20 (see [0075]). Here, the charged and hydrophobic resides clearly switch or alternate. Moreover, the invention explicitly includes grouping of cationic segments of at least five contiguous amino acids with hydrophobic segments of at least five contiguous amino acid residues in synthetic copolypeptides and multimeric structures (see claim 21). Here, Applicant has argued that the residues are not arranged in a substantially alternating pattern. As discussed below, the phrase “substantially alternating” is indefinite in this context, seeing as it is a relative term that is not defined in the claims or specification and does not have a well-known meaning in the art. Under the broadest reasonable interpretation of the term “substantially” in the phrase “substantially alternating,” copolypeptides like poly(L-lysine-HCl)55-block-poly(racemic-hydrophobic amino acid)20 of Bevilacqua et al. contain at least one transition from charged segments of amino acids to hydrophobic segments as a part of a copolypeptide. Given the broadest reasonable interpretation of “substantially” in this context, the structure poly(L-lysine-HCl)55-block-poly(racemic-hydrophobic amino acid)20 of Bevilacqua et al. fulfills the limitation of alternating between charged and hydrophobic amino acid residues.
The requirement is still deemed proper and is therefore made FINAL.
Claims 2, 13-14, 36, 68, and 71-74 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species or group of inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/28/2026. Although Applicant included in the response to the requirement for restriction and election of species that the elected species read on claim 36, the claim recites a peptide that includes a functional group, but the elected species does not include a functional group. As such, claim 36 is withdrawn for being drawn to unelected species.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Information Disclosure Statement
The information disclosure statements (IDS) were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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, 3-4, 7-11, 15, 20, 32, 36, 50, 54-57, 62, 65-67, and 69-70 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for killing microbes, specifically, P. aeruginosa, C. albicans, E. coli, A. fumigatus, S. aureas, E. facecium, S. epidermidis, S. haemolyticus, K. pneumonia, and A. baumanii, via topical administration of PEP6R, PEP8R, PEP4R, and PEP2R hydrogels on growth-permitting surfaces like agar plates, via injections, or in wounds or wound dressings, does not reasonably provide enablement for all methods of using all hydrogels of claim 1 to kill all fungal organisms in all subjects. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
With regard to the breadth of the claims, the nature of the invention, and the state of the prior art, the method of claim 1 includes any manner of administering the hydrogel of claim 1 to deactivate a target fungal organism but does not enable one having ordinary skill in the art to make or use the invention commensurate with this broad scope. The nature of the invention as a fungicidal hydrogel suggests, particularly within the art of methods and materials of killing microorganisms, that the method of deactivating the organisms depends on the manner administration and on the specific composition of the hydrogel. In other words, it is well recognized that the method, manner, or mode of administration affects the efficacy of a material capable of deactivating microorganisms, and that antimicrobial materials are generally specific with regard to the microorganism or class of microorganisms targeted. For example, the efficacy of the fungicidal hydrogel may depend on whether the hydrogel comes in direct contact with the fungal organism, rather than simply being “administered to the target site.” Beyond this, the efficacy will depend on whether the hydrogel is specific for deactivating the particular microorganism or class of microorganism. Moreover, with regard to the level of ordinary skill and the level of predictability in the art, it is not clear which methods or manners of administering the hydrogel to the target fungal organism will achieve the intended result of the method, as discussed in the examples above and below. Here, one having ordinary skill in the art would not reliably be able to predict which methods would achieve the result, and there are not examples disclosed to cover a representative sample of methods. Moreover, they would not reasonably be able to predict whether the hydrogel will be specific for any particular microorganism. With regard to the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention based on the content of the disclosure, as discussed above, the method of claim 1 includes the limitation that an “amount” of fungicidal hydrogel effective to deactivate the target fungal organism is administered, but it does not include a limitation on the method of use. As in the example discussed above, there exist many manners in which an amount effective to deactivate the target organism can be administered in a manner that does not necessarily enable one having ordinary skill in the art to make or use the invention. Moreover, although the examples of the instant application include treating P. aeruginosa, C. albicans, E. coli, A. fumigatus, S. aureas, E. facecium, S. epidermidis, S. haemolyticus, K. pneumonia, and A. baumanii, they do not provide a representative sample of treating fungal infections to enable one having ordinary skill in the art to reasonably make and use the invention commensurate with the scope of treating any fungal infection in any subject or target site, as claimed in claim 1. In other words, the disclosure has not provided direction or examples to reasonably enable a person having ordinary skill in the art to reasonably be enabled to deactivate any fungal organism in any subject via any mechanism of administration. Here, the working examples do not cover a representative sample of methods or manners of administering the fungicidal hydrogel to represent any method of administration as claimed. Given this, one having ordinary skill in the art would not be enabled to make or use the invention commensurate with this scope.
Claim Rejections - 35 USC § 112
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 7 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “sterilize” in claim 7 is used by the claim to mean “reduce,” “eliminate,” “remove,” “kill,” or “destroy” a portion of a population of a microbe while the accepted meaning is “refers to any process that removes, kills, or deactivates all forms of life (particularly microorganisms such as fungi, bacteria, spores, and unicellular eukaryotic organisms) and other biological agents (such as prions or viruses) present in fluid or on a specific surface or object.” Under this accepted meaning, it is not possible to sterilize part of a population of fungal organism at a target site. The term “sterilize” is indefinite because one having ordinary skill in the art would not be able to assess the metes and bounds of the term in light of the fact that it has a different meaning in the art as compared to its use in the disclosure. The term is therefore indefinite because the specification does not clearly redefine the term. Here, the term is interpreted under the broadest reasonable interpretation to mean “remove.” Claim 7 recites a method of claim 1 wherein the amount is sufficient to sterilize at least 90% of the target fungal organism at the target site. Applicant does not distinctly or particularly point out what is meant by the phrase “sterilize at least 90% of the target fungal organism.” Here, it is not clear what the reduction of at least 90% is compared to. In other words, it is not clear if the sterilization of at least 90% is compared to a no-peptide control, to a measure of the starting amount of fungal organism, or another measure.
Claim Interpretation
As discussed above, the term “sterilize” is indefinite because one having ordinary skill in the art would not be able to assess the metes and bounds of the term in light of the fact that it has a different meaning in the art as compared to its use in the disclosure. The term is therefore indefinite because the specification does not clearly redefine the term. Here, the term is interpreted under the broadest reasonable interpretation to mean “remove” or “kill.”
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 9, 10, 50, 65, 66, and 69 rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US 20150366193 A1, hereinafter Bevilacqua et al.
With regard to claim 1, Bevilacqua et al. teach treating wounds and other infections comprising administering an antimicrobial composition comprising: at least one species of synthetic copolypeptide of at least forty amino acid residues comprising: at least one hydrophilic segment containing at least five contiguous cationic amino acid residues; and at least one hydrophobic segment containing at least five contiguous hydrophobic amino acid residues; and water; wherein the composition of said copolypeptide in aqueous media forms structures, including hydrogels (see [0027], [0089]); and wherein the composition inhibits or kills microbes (see claim 1, paragraph [0078], and Abstract). The diblock synthetic coploypeptides based on cationic amino acid lysine and other hydrophobic amino acids are also shown to be effective against certain fungal organisms as depicted for Candida albicans (see FIG. 6, [0078]).
With regard to claim 3, Bevilacqua et al. teach that the peptides and hydrogels of their invention may directly bind to damaged tissues where they may provide a local, concentrated antimicrobial activity (see [0097], [0099]).
With regard to claims 9 and 10, as discussed above, Bevilacqua et al. teach that the diblock synthetic coploypeptides based on cationic amino acid lysine and other hydrophobic amino acids are also shown to be effective against certain fungal organisms as depicted for Candida albicans (see FIG. 6, [0078]).
With regard to claim 50, Bevilacqua et al. teach that 1 w/v % polypeptide solution is used in creating the emulsion (see [0133]).
With regard to claim 65, as discussed above, the diblock synthetic coploypeptides based on cationic amino acid lysine and other hydrophobic amino acids are also shown to be effective against certain fungal organisms as depicted for Candida albicans (see FIG. 6, [0078]). Further, they teach that the inventive synthetic copolypeptides are useful in treatment of wounds and other infections (see Abstract).
With regard to claim 66, as discussed above, the diblock synthetic coploypeptides based on cationic amino acid lysine and other hydrophobic amino acids are also shown to be effective against certain fungal organisms as depicted for Candida albicans (see FIG. 6, [0078]). Further, they teach that the inventive synthetic copolypeptides are useful in treatment of wounds and other infections (see Abstract).
With regard to claim 69, Bevilacqua et al. teach that the antimicrobials can undergo directed self-assembly (see Abstract).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 3, 4, 7, 15, 20, 50, 54, 55, 66, 67, 69, and 70 are rejected under 35 U.S.C. 103 as being unpatentable over Veiga et al. (submitted on IDS filed 10/06/2023, Veiga, Ana Salomé et al. “Arginine-rich self-assembling peptides as potent antibacterial gels.” Biomaterials vol. 33,35 (2012): 8907-16) in view of Cascales et al. (López Cascales, José Javier et al. “Small Cationic Peptides: Influence of Charge on Their Antimicrobial Activity.” ACS omega vol. 3,5 (2018): 5390-5398).
With regard to claim 1, Veiga et al. teach a method of treating bacterial infections comprising administering a preparation comprising hydrogels of self-assembling ß-hairpin peptides, including SEQ ID NO: 2 of the instant application, VKVRVRVRVPPTRVRVRVKV (PEP6R), an amphiphilic peptide (see Abstract, page 8912, paragraph 3). In antibacterial assays, they further teach using the peptides in an aqueous buffer, BTP, with water and sodium chloride (see page 8909, paragraph 8 and page 8910, paragraph 1), and they teach that all peptides were purified as a part of the peptide synthesis (see page 8908, paragraph 4).
Veiga et al. does not teach that the method is drawn to administering an amount effective to promote deactivation of a target fungal organism associated with a fungal contamination.
Cascales et al. teach that a great number of cationic peptides that are the first natural barrier against external pathogens have been discovered and characterized, and that two main characteristics of these cationic peptides are that they have positive charges, ranging from +2 to +9, and that they fold in an amphipathic helical conformation, with two well-defined hydrophilic and hydrophobic faces (see page 5390, paragraph 2). They further teach that, in line with the action mechanism of these antimicrobial peptides, there is a wide consensus that these peptides focus their target on the destabilization of the cell membrane of Gram-negative and Gram-positive bacteria and fungus (see page 5390, paragraph 4 and page 5391, paragraph 1). They argue that these peptides exert their lytic activity against pathogens by electrostatic interactions with the negative charge of the microbial cell surfaces (favored by the positive charge of these cationic peptides) and subsequent pathogen membrane disruption, meaning that the positive charge of the cationic peptide seems to be a crucial aspect that needs to be considered in the discrimination process between the pathogen and host cells (see page 5391, paragraph 1). In other words, the positive charge of these peptides, together with the amphipathic nature of their alpha helical conformation, seems to be key aspects for their antibacterial and antifungal activity, particularly for peptides with a charge less than or equal to +9 (see page 5391, paragraph 2). Given this, Cascales et al. provide a clear motivation and explanation for why small, positively charged, amphiphilic peptides with antibacterial activity may also have antifungal activity. Specifically, they argue that the positive charge interacts with the cell membrane of bacterial or fungal pathogens. As such, they provide a clear motivation for the use of positively charged (less than or equal to +9) amphiphilic small peptides with antibacterial activity in treating fungal pathogens with a reasonable expectation of success. Here, Veiga et al. explicitly teach that the net formal charge of PEP6R at neutral pH is +9 per monomer (see page 8912, paragraph 6). Given this clear motivation, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Cascales et al. and Veiga et al. to use the invention of Veiga et al. to treat fungal contaminations.
With regard to claim 3, as discussed above, Veiga et al. teach a method of treating bacterial infections as recited above, and they teach that the hydrogels display inherent activity against bacteria and can be used to directly treat accessible wounds to prevent or kill existing bacteria (see Abstract). As such, they teach locally applying the hydrogel treatment to kill bacteria in an accessible wound, but they do not teach the method wherein the target site is a local site of a fungal contamination. As discussed above, Cascales et al. provide a clear motivation for using the method of Veiga et al. to treat fungal infections. Given the reasoning to combine the references of Cascales et al. and Veiga et al. discussed above, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to apply the method of Veiga et al. to treat fungal contaminations in place of the bacterial contaminations taught by Veiga et al.
With regard to claim 4, Veiga et al. teach the use of an acetate counterion, TFA, in the peptide synthesis, and they do not teach the use of chloride in any form in the synthesis of the peptide (see page 8908, paragraph 4). As such, they teach a peptide according to the claim limitations that does not have chloride counterions, seeing as chloride-containing compounds are not used in the peptide synthesis, and a different counterion, an acetate, is used.
With regard to claim 7, as discussed above, the term “sterilize” is indefinite in the context of the invention, and the term is interpreted under the broadest reasonable interpretation to mean “remove.” Here, Veiga et al. teach the method discussed above, but they do not teach that the method comprises administering an amount sufficient to remove at least 90% of the target fungal organism at the target site. Lopez et al. teach a method of treating fungal contaminations using amphiphilic, cationic, ß-peptides (see Abstract). They motivate the use of these peptides in treating fungal contaminations on account of the observation that the peptides lowered the minimum biofilm prevention concentrations (MBPCs) of-peptides by up to 128-fold (see Abstract). Lopez et al. also teach small cationic antifungal β-peptides at a concentration that resulted in at least 90% reduction in C. albicans biofilm compared to a no-peptide control (see page 3, paragraph 1). Given the substantial reduction in MBPC and the 90% reduction in C. albicans, Lopez provide a clear motivation for the of their effective concentrations of small cationic, amphiphilic peptide formations. As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Lopez et al. and Veiga et al. with a reasonable expectation of removing or killing 90% of C. albicans microorganisms.
With regard to claim 15, Cascales et al. teach topical applications of the cationic and amphiphilic peptides because peptides that have negligible lethality and toxicity for mammalian cells in vitro have frequently been found to be toxic when they were injected into the bloodstream (see page 5391, paragraph 3). Given the motivation to combine the references of Veiga et al. and Cascales et al. discussed above, as well as the clear motivation to use topical administration for the cationic and amphiphilic peptides of Cascales et al., it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Veiga et al. and Cascales et al. to use the method of Veiga et al. with topical administration.
With regard to claim 20, as discussed above, Veiga et al. teach the peptide of SEQ ID NO: 2, VKVRVRVRVPPTRVRVRVKV, of the instant application (see Abstract), and this is the elected species that reads on claim 20 of the instant application. Here, products of identical chemical composition cannot have mutually exclusive properties (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 PEP6R inherently has the folding group, turn sequence, and residues recited in claim 20 of the instant application.
With regard to claim 50, Veiga et al. teach PEP6R gels prepared at 1.5 wt % or higher concentration, which demonstrated high antimicrobial activity (see Abstract). Beyond this, they teach that Aat 0.5 wt% the hydrogel surface of PEP2R shows minimal action, but as the wt% is increased, the gel surface gains activity in a wt%-dependent manner wherein 2 wt% gels inhibit proliferation of about 50% of the introduced bacteria as compared to about 10% in the 0.5 wt% gel (see page 8911, paragraph 2). Given the reasoning to combine the references recited above, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to use the method of Veiga et al. to treat fungal infections. Although this range, roughly from 0.5% to 2% w/v, does not overlap exactly with the claimed range of 0.5% to 3.0% w/v, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) A claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" was considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." Here, given that the ranges are nearly entirely overlapping, a case of obviousness exists.
With regard to claims 54 and 55, as discussed above, Veiga et al. teach the peptide of SEQ ID NO: 2 of the instant application, VKVRVRVRVPPTRVRVRVKV (PEP6R) (see Abstract). Veiga et al. teach that the net formal charge of PEP6R at neutral pH is +9 per monomer (see page 8912, paragraph 6). Although this value, +9, does not entirely overlap with the claimed ranged +2 to +11 or +5 to +9, as discussed above, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) A claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" was considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." Here, given that the peptide of SEQ ID NO: 2 falls within each range, a case of obviousness exists.
With regard to claim 66, Veiga et al. teach that hydrogel materials that display inherent activity against bacteria can be used to directly treat accessible wounds to prevent or kill existing infection, that hydrogels composed of self-assembling ß-hairpin peptides, having a high content of arginine, are extremely effective antimicrobials (see Abstract).
With regard to claim 67, as discussed above, Veiga et al. teach that hydrogel materials that display inherent activity against bacteria can be used to directly treat accessible wounds to prevent or kill existing infection, that hydrogels composed of self-assembling ß-hairpin peptides, having a high content of arginine, are extremely effective antimicrobials (see Abstract). They also teach that microbial infections are a common problem associated with dermal wounds, within which P. aeruginosa accounts for 10% of all hospital infections, and this is particularly relevant for patients with cancer, AIDS, burns, or cystic fibrosis (see page 8907, paragraph 1). Seeing as the hydrogels of the invention of Veiga et al. are extremely effective against P. aeruginosa (see Abstract), there exists a clear motivation to use this hydrogel to treat the patients that Veiga et al. identity as affected by P. aeruginosa, namely hospitalized patients with cancer, AIDS, burns, or cystic fibrosis (see Abstract and page 8907, paragraph 1). As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to use the hydrogels of Veiga et al. to treat trauma wounds, specifically burns.
With regard to claim 69, Veiga et al. teach the use of a buffer comprising 150 mM sodium chloride and 50 mM BTP (see page 8910, paragraph 1). They explicitly teach using this buffer along with the peptides directly in wells of tissue-culture treated plates to test its antimicrobial ability (see page 8910, paragraph 1). Here, the buffer is therefore used at the target site (see page 8910, paragraph 1). Moreover, Veiga et al. teach that the addition of buffer triggers peptide folding, self-assembly (see page 8910, paragraph 1).
With regard to claim 70, Veiga et al. teach the use of a buffer comprising 150 mM sodium chloride and 50 mM BTP (see page 8910, paragraph 1). As discussed above, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) A claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" was considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." Here, given that the value of Veiga et al. falls within the range, a case of obviousness exists.
Claims 1, 3-4, 7-11, 15, 20, 32, 36, 50, 54-57, 65-67, and 69-70 are rejected under 35 U.S.C. 103 as being unpatentable over Veiga et al. (submitted on IDS filed 10/06/2023, Veiga, Ana Salomé et al. “Arginine-rich self-assembling peptides as potent antibacterial gels.” Biomaterials vol. 33,35 (2012): 8907-16) in view of Cascales et al. (López Cascales, José Javier et al. “Small Cationic Peptides: Influence of Charge on Their Antimicrobial Activity.” ACS omega vol. 3,5 (2018): 5390-5398), as applied to claims 1, 3, 7, 15, 20, 0, 54, 55, 66, 67, 69, and 70 above and in further view of US Patent No. 10,548,944 B1, hereinafter Jaynes et al.
The teachings of Veiga et al. and Cascales et al. have been set forth above.
With regard to claim 8, Veiga et al. additionally teach the method of treating microbial infections using the hydrogels discussed above. Specifically, Veiga et al. teach a method of treating bacterial infections comprising administering a preparation comprising hydrogels of self-assembling ß-hairpin peptides, including SEQ ID NO: 2 of the instant application, VKVRVRVRVPPTRVRVRVKV (PEP6R), an amphiphilic peptide (see Abstract, page 8912, paragraph 3). They do not, however, teach that the method is drawn to administering an amount effective to promote deactivation of a target fungal organism associated with a fungal contamination. As discussed above, Cascales et al. provide a clear motivation for using peptides like those used to form the hydrogel of Veiga et al. in treating fungal contaminations. Neither reference, however, teaches treating biofilms.
Jaynes et al. teach peptides having potent antimicrobial activity, broad-spectrum antimicrobial activity, and/or the ability to kill otherwise antibiotic-resistant microbes, or microbes protected by biofilms (see Abstract). More specifically, they teach amphipathic/amphiphilic peptides with cationic charges, including +9 (see column 9, lines 36-40). They teach peptides with positive charges on their polar surface, including the peptide RP557, are capable of interacting with and disrupting the negatively charged phospholipids on the cell membranes of microorganisms (see column 35, lines 9-12). They further teach that the RP557 peptide, which is characterized as a short, amphiphilic/amphipathic, cationic peptide, prevents and treats biofilms of various bacterial and fungal species like Candida albicans found in wounds thereby mitigating the influence of infection on healing and regeneration (see column 35, lines 65-67, column 36, lines 1-3, and Fig. 5A to 5B). Here, Jaynes et al. provide a clear motivation for the use of small, cationic, amphiphilic peptides in treating fungal infections like Candida albicans because of the fact that the positive charges of the peptides interact with and disrupt the negatively charged phospholipids of the microorganism membrane. Beyond this, Jaynes et al. also provide a motivation for using hydrogel forms of the treatment because they represent a convenient topical ophthalmic delivery system (see column 26, lines 10-18). Given the motivations for using small, cationic, amphiphilic peptides with +9 charge in treating fungal infections, as well as the motivation for using the treatments of the invention of Jaynes et al. in hydrogels, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references and use the method of Veiga et al. to treat fungal biofilms.
With regard to claims 9 and 10, as discussed above, Jaynes et al. teach peptides having potent antimicrobial activity, broad-spectrum antimicrobial activity, and/or the ability to kill otherwise antibiotic-resistant microbes, or microbes protected by biofilms (see Abstract). They teach peptides with positive charges on their polar surface, including the peptide RP557, are capable of interacting with and disrupting the negatively charged phospholipids on the cell membranes of microorganisms (see column 35, lines 9-12). They further teach that the RP557 peptide, which is characterized as a short, amphiphilic/amphipathic, cationic peptide, prevents and treats biofilms of various bacterial and fungal species like Candida albicans found in wounds thereby mitigating the influence of infection on healing and regeneration (see column 35, lines 65-67, column 36, lines 1-3, and Fig. 5A to 5B). Again, given the reasoning discussed above, it would have been obvious to combine the references of Jaynes et al. and Veiga et al. to use the method of Veiga et al. in treating Candida albicans.
With regard to claim 11, Jaynes et al. teach that the subject peptide composition, alone or in combination with antibiotic and/or anti-inflammatory agents, is applied to burn wounds as a gel, ointment or cream, and/or administered systemically (see column 26, lines 64-67). Topical application can prevent systemic infection following superficial colonization or eradicate a superficial infection (see columns 26, line 67 and column 27, lines 1-2). In some cases, the subject composition can be administered as a 0.5% to 5% gel, cream, or ointment, such as 0.5 to 2%, as described herein, and application to the skin could be performed once a day or as often as dressings are changed (see column 27, lines 2-6). Here, Jaynes et al. teach topical application to the skin, an integumental tissue. Given the reasoning discussed above, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Jaynes et al. and Veiga et al. to use the method of Veiga et al. in treating fungal infections according to the methods of Jaynes et al.
With regard to claim 32, Jaynes et al. teach using the cationic amphiphilic peptides, specifically the peptide RP557 discussed above, at 98% purity or better (see column 35, lines 13-14). Again, given the reasoning provided above, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references.
With regard to claim 56, Jaynes et al. teach that the composition is a lyophilized composition that can be provided to an end use in a solid form suitable for reconstitution with a liquid, e.g., an aqueous solution (see column 20, lines 41-44).
With regard to claim 57, Jaynes et al. teach the compositions of their invention can function as sterilizing agents and can serve as sterile storage media (see column 23, lines 7-20).
With regard to claim 65, Jaynes et al. teach treating fungal infections in rats, specifically vulvovaginal candidiasis caused by C. albicans (see column 36, lines 52-55 and column 2, lines 64-67).
Claims 1, 3-4, 7-11, 15, 20, 32, 36, 50, 54-57, 62, 65-67, and 69-70 are rejected under 35 U.S.C. 103 as being unpatentable over Veiga et al. (submitted on IDS filed 10/06/2023, Veiga, Ana Salomé et al. “Arginine-rich self-assembling peptides as potent antibacterial gels.” Biomaterials vol. 33,35 (2012): 8907-16) in view of Cascales et al. (López Cascales, José Javier et al. “Small Cationic Peptides: Influence of Charge on Their Antimicrobial Activity.” ACS omega vol. 3,5 (2018): 5390-5398), as applied to claims 1, 3, 7, 15, 20, 0, 54, 55, 66, 67, 69, and 70 above and in further view of US Patent No. 10,548,944 B1, hereinafter Jaynes et al. and Namgoong et al. (Namgoong, Sik et al. “Clinical experience with surgical debridement and simultaneous meshed skin grafts in treating biofilm-associated infection: an exploratory retrospective pilot study.” Journal of plastic surgery and hand surgery vol. 54,1 (2020): 47-54).
The teachings of Veiga et al., Cascales et al., and Jaynes et al. have been set forth above.
With regard to claim 62, Jaynes et al. teach that infection is the predominant determinant of wound healing, incidence of complications, and outcome of burn patients, and that frequent debridements and establishment of an epidermis or a surrogate, such as a graft or a skin substitute, significantly aids in the prevention of infection (see column 26, lines 57-63). Here, Jaynes et al. provide a clear motivation for frequent debridement of a wound area on account of its ability to prevent infection. Moreover, they teach local topical application directly to wounds or areas in need of treatment (see column 22, lines 1-9). They also teach that the subject peptide composition, alone or in combination with antibiotic and/or anti-inflammatory agents, is applied to burn wounds as a gel, ointment or cream, and/or administered systemically (see column 26, lines 64-67). Although Jaynes et al. clearly motivate debridement of the wound and application of the peptide composition directly to the wound area in need of treatment, they do not explicitly say that debridement is done prior to applying the antimicrobial composition. Here, Namgoong et al. teach that it is known in the art (i.e. in current treatment guidelines) that debridement is done prior to applying antimicrobials to facilitate the wound becoming self-sustaining in terms of a positive wound-healing trajectory (see Abstract). This provides a clear motivation to use debridement of the target area prior to applying antimicrobials, which facilitate the healing of the wound. Seeing as Jaynes et al. teach the use of debridement to prevent infection, and given this clear motivation from Namgoog et al., it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references and perform debridement before applying the antimicrobials.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-4, 7, 15, 20, 0, 54, 55, 69, and 70 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 42, 28, 46, 47, 55, 73, 77, and 83 of copending Application No. 18/682493 (reference application), hereinafter Mehta et al. (493) in view of Veiga et al. (submitted on IDS filed 10/06/2023, Veiga, Ana Salomé et al. “Arginine-rich self-assembling peptides as potent antibacterial gels.” Biomaterials vol. 33,35 (2012): 8907-16) and Cascales et al. (López Cascales, José Javier et al. “Small Cationic Peptides: Influence of Charge on Their Antimicrobial Activity.” ACS omega vol. 3,5 (2018): 5390-5398).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
With regard to claim 1, Mehta et al. (493) claim a method of treating a nerve injury, comprising: administering to a target site of a nerve injury a preparation comprising a purified amphiphilic peptide in an aqueous biocompatible solution, the peptide comprising a folding group having a plurality of charged amino acid residues and hydrophobic amino acid residues arranged in a substantially alternating pattern and a turn sequence, the peptide being configured to self-assemble into a hydrogel, in an amount effective to treat the nerve injury (see claim 1 of the reference application). Moreover, they claim that the folding group has a sequence comprising Y[XY]N[T][YX]MY, where X is 1-3 charged amino acids, Y is 1-3 hydrophobic amino acids, T is 2-8 turn sequence amino acids, and N and M are each independently between 2 and 10, and wherein the turn sequence amino acids are independently selected from a D-proline, an L- proline, aspartic acid, threonine, asparagine, and combinations thereof (see claims 46 and 47). This sequence includes SEQ ID NO: 2 of both the reference and the instant application, which the instant application elected as the peptide sequence for the hydrogel. Mehta et al. (493) do not, however, explicitly claim the use of the hydrogel with this sequence for treating fungal contamination.
As discussed above, Veiga et al. teach a method of treating bacterial infections comprising administering a preparation comprising hydrogels of self-assembling ß-hairpin peptides, similarly including SEQ ID NO: 2 of the instant application, VKVRVRVRVPPTRVRVRVKV (PEP6R), an amphiphilic peptide (see Abstract, page 8912, paragraph 3). In antibacterial assays, they further teach using the peptides in an aqueous buffer, BTP, with water and sodium chloride (see page 8909, paragraph 8 and page 8910, paragraph 1), and they teach that all peptides were purified as a part of the peptide synthesis (see page 8908, paragraph 4). Here, Veiga et al. provide a clear motivation for using the peptide of the hydrogel of Mehta et al. (493) in treating microbial infections, particularly bacterial infections. As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to use the method of Mehta et al. (493) in treating bacterial infections. Again, Veiga et al. does not teach that the method is drawn to administering an amount effective to promote deactivation of a target fungal organism associated with a fungal contamination.
Cascales et al. teach that a great number of cationic peptides that are the first natural barrier against external pathogens have been discovered and characterized, and that two main characteristics of these cationic peptides are that they have positive charges, ranging from +2 to +9, and that they fold in an amphipathic helical conformation, with two well-defined hydrophilic and hydrophobic faces (see page 5390, paragraph 2). They further teach that, in line with the action mechanism of these antimicrobial peptides, there is a wide consensus that these peptides focus their target on the destabilization of the cell membrane of Gram-negative and Gram-positive bacteria and fungus (see page 5390, paragraph 4 and page 5391, paragraph 1). They argue that these peptides exert their lytic activity against pathogens by electrostatic interactions with the negative charge of the microbial cell surfaces (favored by the positive charge of these cationic peptides) and subsequent pathogen membrane disruption, meaning that the positive charge of the cationic peptide seems to be a crucial aspect that needs to be considered in the discrimination process between the pathogen and host cells (see page 5391, paragraph 1). In other words, the positive charge of these peptides, together with the amphipathic nature of their alpha helical conformation, seems to be key aspects for their antibacterial and antifungal activity, particularly for peptides with a charge less than or equal to +9 (see page 5391, paragraph 2). Given this, Cascales et al. provide a clear motivation and explanation for why small, positively charged, amphiphilic peptides with antibacterial activity may also have antifungal activity. Specifically, they argue that the positive charge interacts with the cell membrane of bacterial or fungal pathogens. As such, they provide a clear motivation for the use of positively charged (less than or equal to +9) amphiphilic small peptides with antibacterial activity in treating fungal pathogens with a reasonable expectation of success. Here, Veiga et al. explicitly teach that the net formal charge of PEP6R at neutral pH is +9 per monomer (see page 8912, paragraph 6), and Mehta et al. (493) teach the same peptide as that of Veiga et al., as discussed above (see claims 46 and 47). Given this clear motivation, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Cascales et al., Veiga et al., and Mehta et al. (493) to use the peptides of Veiga et al. and Mehta et al. (493) to treat fungal contaminations.
With regard to claim 3, as discussed above, Veiga et al. teach a method of treating bacterial infections as recited above, and they teach that the hydrogels display inherent activity against bacteria and can be used to directly treat accessible wounds to prevent or kill existing bacteria (see Abstract). As such, they teach locally applying the hydrogel treatment to kill bacteria in an accessible wound, but they do not teach the method wherein the target site is a local site of a fungal contamination. As discussed above, Cascales et al. provide a clear motivation for using the method of Veiga et al. to treat fungal infections. Given the reasoning to combine the references of Mehta et al. (493), Cascales et al., and Veiga et al. discussed above, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to apply the method of Veiga et al. and peptides of Mehta et al. (493) to treat fungal contaminations in place of the bacterial contaminations taught by Veiga et al. and nerve conditions taught by Mehta et al. (493) (see claim 1).
With regard to claim 4, Mehta et al. (493) claim the method discussed above wherein the peptide comprises an effective amount of acetate, citrate, and/or chloride counterions (see claims 39, 4, and 41), and that the peptide is substantially free of chloride counterions. Given that the counterions are claimed in the alternative, the claims clearly include embodiments wherein the counterions are acetate or citrate and not chloride.
With regard to claim 7, as discussed above, Mehta et al. (493) teach the method of claim 1 with the same chemical composition as claimed in claim 1 of the instant application. Specifically, they claim that the folding group has a sequence comprising Y[XY]N[T][YX]MY, where X is 1-3 charged amino acids, Y is 1-3 hydrophobic amino acids, T is 2-8 turn sequence amino acids, and N and M are each independently between 2 and 10, and wherein the turn sequence amino acids are independently selected from a D-proline, an L- proline, aspartic acid, threonine, asparagine, and combinations thereof (see claims 46 and 47). This sequence includes SEQ ID NO: 2 of both the reference and the instant application, which the instant application elected as the peptide sequence for the hydrogel. Although Mehta et al. (493) do not explicitly claim the use of the hydrogel with this sequence for treating fungal contamination, “products of identical chemical composition cannot have mutually exclusive properties" (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.
With regard to claims 8-10, as discussed above, Mehta et al. (493) claim the method discussed above wherein the folding group has a sequence comprising Y[XY]N[T][YX]MY, where X is 1-3 charged amino acids, Y is 1-3 hydrophobic amino acids, T is 2-8 turn sequence amino acids, and N and M are each independently between 2 and 10, and wherein the turn sequence amino acids are independently selected from a D-proline, an L- proline, aspartic acid, threonine, asparagine, and combinations thereof (see claims 46 and 47). This sequence includes SEQ ID NO: 2 of both the reference and the instant application, which the instant application elected as the peptide sequence for the hydrogel. Although Mehta et al. (493) do not explicitly claim the use of the hydrogel with this sequence for treating fungal contamination, “products of identical chemical composition cannot have mutually exclusive properties" (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. Moreover, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer" (Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999)). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable (In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)). Here, applying the method of Mehta et al. (493) to treating a different target organism because of the discovery of an unappreciated property in treating fungal organisms does not make the claim patentable.
With regard to claim 11, Mehta et al. (493) claim treating nervous tissue (see claim 3).
With regard to claim 15, Mehta et al. (493) claim topical, parenteral, and enteral administration (see claim 28).
With regard to claim 20, Mehta et al. (493) claim the method discussed above wherein: the hydrophobic amino acid residues are independently selected from glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, threonine, tryptophan, and combinations thereof; and the charged amino acid residues are independently selected from arginine, lysine, histidine, and combinations thereof (see claim 46). They further claim the method wherein the folding group has a sequence comprising Y[XY]N[T][YX]MY, where X is 1-3 charged amino acids, Y is 1-3 hydrophobic amino acids, T is 2-8 turn sequence amino acids, and N and M are each independently between 2 and 10, and wherein the turn sequence amino acids are independently selected from a D-proline, an L- proline, aspartic acid, threonine, asparagine, and combinations thereof (see claim 47).
With regard to claim 32, Mehta et al. (493) claim the method discussed above wherein the peptide is at least 80% purified (see claim 55).
With regard to claim 50, Mehta et al. (493) claim the method discussed above wherein the preparation comprises between 0.1% w/v and 8.0% w/v of the peptide (see claim 73). Although this is range is not identical to the claimed range of the instant application, "a prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness" (In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005) (claimed alloy held obvious over prior art alloy that taught ranges of weight percentages overlapping, and in most instances completely encompassing, claimed ranges; furthermore, narrower ranges taught by reference overlapped all but one range in claimed invention). Here, the range of Mehta et al. (493) encompasses the claim of the instant application and is not so broad as to encompass a very large number of possible distinct compositions.
With regard to claims 54 and 55, Mehta et al. (493) claim the method discussed above wherein the peptide is cationic or anionic, the cationic peptide having a net charge of from +2 to +11 (see claim 77). Again, although this is range is not identical to the claimed range of the instant application, "a prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness" (In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005) (claimed alloy held obvious over prior art alloy that taught ranges of weight percentages overlapping, and in most instances completely encompassing, claimed ranges; furthermore, narrower ranges taught by reference overlapped all but one range in claimed invention). Here, the range of Mehta et al. (493) encompasses the claim of the instant application and is not so broad as to encompass a very large number of possible distinct compositions.
With regard to claim 57, Mehta et al. claim the method discussed above wherein the preparation is sterilized by autoclave sterilization (see claim 83).
With regard to claim 65, as discussed above, Mehta et al. (493) claim a method of treating a nerve injury, comprising: administering to a target site of a nerve injury a preparation comprising a purified amphiphilic peptide in an aqueous biocompatible solution, the peptide comprising a folding group having a plurality of charged amino acid residues and hydrophobic amino acid residues arranged in a substantially alternating pattern and a turn sequence, the peptide being configured to self-assemble into a hydrogel, in an amount effective to treat the nerve injury (see claim 1 of the reference application). Moreover, they claim that the folding group has a sequence comprising Y[XY]N[T][YX]MY, where X is 1-3 charged amino acids, Y is 1-3 hydrophobic amino acids, T is 2-8 turn sequence amino acids, and N and M are each independently between 2 and 10, and wherein the turn sequence amino acids are independently selected from a D-proline, an L- proline, aspartic acid, threonine, asparagine, and combinations thereof (see claims 46 and 47). This sequence includes SEQ ID NO: 2 of both the reference and the instant application, which the instant application elected as the peptide sequence for the hydrogel. Although Mehta et al. (493) do not explicitly claim the use of the hydrogel with this sequence for treating fungal contamination, “products of identical chemical composition cannot have mutually exclusive properties" (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. Moreover, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer" (Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999)). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable (In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)).
With regard to claims 69 and 70, Mehta et al. (493) claim the method discussed above, further comprising administering to the target site a buffer comprising an effective amount of an ionic salt and a biological buffering agent to form the hydrogel, wherein the buffer comprises between about 10 mM and 150 mM sodium chloride and between about 10 mM and 100 mM Bis-tris propane (BTP) (see claim 42).
Claims 1, 3-4, 7-11, 15, 20, 32, 36, 50, 54-57, 62, 65-67, and 69-70 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7, 10, 14, 19, 31, 49, 53-56, 61, 64-66, and 68-69 of copending Application No. 18/040388 (reference application), hereinafter Kumar et al. in view of Veiga et al. (submitted on IDS filed 10/06/2023, Veiga, Ana Salomé et al. “Arginine-rich self-assembling peptides as potent antibacterial gels.” Biomaterials vol. 33,35 (2012): 8907-16) and Cascales et al. (López Cascales, José Javier et al. “Small Cationic Peptides: Influence of Charge on Their Antimicrobial Activity.” ACS omega vol. 3,5 (2018): 5390-5398).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
With regard to claim 1, Kumar et al. claim a method of treating a microbial contamination associated with a community of microorganisms of a subject in need thereof, comprising administering to a target site of the subject a thermally stable preparation comprising a purified amphiphilic peptide in an aqueous biocompatible solution, the peptide comprising a folding group having a plurality of charged amino acid residues and hydrophobic amino acid residues arranged in a substantially alternating pattern and a turn sequence, the peptide being configured to self-assemble into a hydrogel, in an amount effective to promote deactivation of a target microorganism associated with the microbial contamination (see claim 1). Kumar et al. claim the method discussed above wherein the folding group has a sequence comprising Y[XYlN[T][YX1MY, where X is 1-3 charged amino acids, Y is 1-3 hydrophobic amino acids, T is 2-8 turn sequence amino acids, and N and M are each independently between 2 and 10;the hydrophobic amino acid residues are independently selected from glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, threonine, tryptophan, and combinations thereof; and the charged amino acid residues are independently selected from arginine, lysine, histidine, and combinations thereof, and the turn sequence amino acids are independently selected from a D-proline, an L-proline, aspartic acid, threonine, asparagine, and combinations thereof (see claim 19). This sequence includes SEQ ID NO: 2 of both the reference and the instant application, VKVRVRVRVPPTRVRVRVKV (PEP6R), which the instant application elected as the peptide sequence for the hydrogel. Kumar et al. do not, however, explicitly claim the use of the hydrogel with this sequence for treating fungal contamination.
Cascales et al. teach that a great number of cationic peptides that are the first natural barrier against external pathogens have been discovered and characterized, and that two main characteristics of these cationic peptides are that they have positive charges, ranging from +2 to +9, and that they fold in an amphipathic helical conformation, with two well-defined hydrophilic and hydrophobic faces (see page 5390, paragraph 2). They further teach that, in line with the action mechanism of these antimicrobial peptides, there is a wide consensus that these peptides focus their target on the destabilization of the cell membrane of Gram-negative and Gram-positive bacteria and fungus (see page 5390, paragraph 4 and page 5391, paragraph 1). They argue that these peptides exert their lytic activity against pathogens by electrostatic interactions with the negative charge of the microbial cell surfaces (favored by the positive charge of these cationic peptides) and subsequent pathogen membrane disruption, meaning that the positive charge of the cationic peptide seems to be a crucial aspect that needs to be considered in the discrimination process between the pathogen and host cells (see page 5391, paragraph 1). In other words, the positive charge of these peptides, together with the amphipathic nature of their alpha helical conformation, seems to be key aspects for their antibacterial and antifungal activity, particularly for peptides with a charge less than or equal to +9 (see page 5391, paragraph 2). Given this, Cascales et al. provide a clear motivation and explanation for why small, positively charged, amphiphilic peptides with antibacterial activity may also have antifungal activity. Specifically, they argue that the positive charge interacts with the cell membrane of bacterial or fungal pathogens. As such, they provide a clear motivation for the use of positively charged (less than or equal to +9) amphiphilic small peptides with antibacterial activity in treating fungal pathogens with a reasonable expectation of success. Here, Kumar et al. explicitly teach that the net formal charge their peptides at neutral pH are between +5 and +9 (see claim 54). Given this clear motivation, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Cascales et al. and Kumar et al. to use the peptides of Kumar et al. to treat fungal contaminations with a reasonable expectation of success.
With regard to claim 3, Kumar et al. claim the method discussed above wherein the target site is a local site of the microbial contamination (see claim 3).
With regard to claim 4, Kumar et al. claim the method discussed above wherein the peptide comprises an effective amount of counterions, to form the hydrogel, the peptide being free of chloride counterions and the counterions selected from acetate and citrate counterions (see claim 4).
With regard to claim 7, Kumar et al. claim the method discussed above wherein the amount is sufficient to sterilize at least 90% of the target microorganism at the target site (see claim 7).
With regard to claims 8, 9, and 10, as discussed above, Kumar et al. claim a method of treating a microbial contamination associated with a community of microorganisms of a subject in need thereof, comprising administering to a target site of the subject a thermally stable preparation comprising a purified amphiphilic peptide in an aqueous biocompatible solution, the peptide comprising a folding group having a plurality of charged amino acid residues and hydrophobic amino acid residues arranged in a substantially alternating pattern and a turn sequence, the peptide being configured to self-assemble into a hydrogel, in an amount effective to promote deactivation of a target microorganism associated with the microbial contamination (see claim 1). Kumar et al. claim the method discussed above wherein the folding group has a sequence comprising Y[XYlN[T][YX1MY, where X is 1-3 charged amino acids, Y is 1-3 hydrophobic amino acids, T is 2-8 turn sequence amino acids, and N and M are each independently between 2 and 10;the hydrophobic amino acid residues are independently selected from glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, threonine, tryptophan, and combinations thereof; and the charged amino acid residues are independently selected from arginine, lysine, histidine, and combinations thereof, and the turn sequence amino acids are independently selected from a D-proline, an L-proline, aspartic acid, threonine, asparagine, and combinations thereof (see claim 19). This sequence includes SEQ ID NO: 2 of both the reference and the instant application, which the instant application elected as the peptide sequence for the hydrogel. Although Mehta et al. (493) do not explicitly claim the use of the hydrogel with this sequence for treating fungal contamination, “products of identical chemical composition cannot have mutually exclusive properties" (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. Moreover, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer" (Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999)). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable (In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)). Here, applying a method of microbial infections broadly to treating pathogenic C. albicans fungal infections or biofilms does not make the method patentable.
With regard to claim 11, Kumar et al. claim the method discussed above wherein the target site is a tissue selected from mesenchymal tissue, connective tissue, muscle tissue, nervous tissue, embryonic tissue, dermal tissue, bone tissue, dental tissue, corneal tissue, cutaneous tissue, integumental tissue, soft tissue, and hard tissue, or a biological fluid selected from tears, mucus, urine, menses, blood, wound exudates, and mixtures thereof (see claim 10).
With regard to claim 15, Kumar et al. claim the method discussed above comprising administering the preparation to a target site of a subject topically, enterally, or parenterally (see claim 14).
With regard to claim 20, Kumar et al. claim the method discussed above wherein the folding group has a sequence comprising Y[XYlN[T][YX1MY, where X is 1-3 charged amino acids, Y is 1-3 hydrophobic amino acids, T is 2-8 turn sequence amino acids, and N and M are each independently between 2 and 10;the hydrophobic amino acid residues are independently selected from glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, threonine, tryptophan, and combinations thereof; and the charged amino acid residues are independently selected from arginine, lysine, histidine, and combinations thereof, and the turn sequence amino acids are independently selected from a D-proline, an L-proline, aspartic acid, threonine, asparagine, and combinations thereof (see claim 19).
With regard to claim 32, Kumar et al. claim the method discussed above wherein the peptide is at least 80% purified (see claim 31).
With regard to claim 50, Kumar et al. claim the method discussed above wherein the preparation comprises between 0.5% w/v and 3.0% w/v of the peptide (see claim 49).
With regard to claim 54, Kumar et al. claim the method discussed above herein the peptide is anionic or cationic, the cationic peptide having has a net charge of from +2 to +11 (see claim 53).
With regard to claim 55, Kumar et al. claim the method discussed above wherein the peptide has a net charge of from +5 to +9 (see claim 54).
With regard to claim 56, Kumar et al. claim the method discussed above wherein the peptide is lyophilized (see claim 55).
With regard to claim 57, Kumar et al. claim the method discussed above wherein the preparation is sterile (see claim 56).
With regard to claim 62, Kumar et al. claim the method discussed above further comprising debridement of the target tissue prior to administration of the preparation (see claim 61).
With regard to claim 65, Kumar et al. claim the method discussed above wherein the microbial contamination is a microbial colonization or infection (see claim 64).
With regard to claim 66, Kumar et al. claim the method discussed above wherein the target site is associated with a wound (see claim 65).
With regard to claim 67, Kumar et al. claim the method discussed above comprising administering the preparation in an amount effective to treat at least one of partial and full thickness wounds (e.g., pressure sores, leg ulcers, diabetic ulcers), first and second degree burns, tunneled/undermined wounds, surgical wounds (e.g., associated with donor sites/grafts, tissue and cell grafts, Post-Moh's surgery, post laser surgery, podiatric, sound dehiscence), trauma wounds (e.g., abrasions, lacerations, burns, skin tears), gastrointestinal wounds (e.g., anal fistulas, diverticulitis, ulcers), and draining wounds (see claim 66).
With regard to claim 69, Kumar et al. claim the method discussed above further comprising administering to the target site a buffer configured to induce self-assembly of the hydrogel (see claim 68).
With regard to claim 70, Kumar et al. claim the method discussed above wherein the buffer comprises between about 10 mM and 150 mM sodium chloride and between about 10 mM and 100 mM Bis-tris propane (BTP) (see claim 69).
Summary
The specification is objected to on the grounds of failing to fulfill sequence requirements for the sequence listing and the use of sequence identifiers. Claims 1, 3-4, 7-11, 15, 20, 32, 36, 50, 54-57, 62, 65-67, and 69-70 are rejected under 35 U.S.C. 112(a) on the grounds of scope of enablement. Claim 7 is rejected under 35 U.S.C. 112(b) on the grounds of failure to distinctly and particularly point out the subject matter that the inventor(s) consider the invention. Claims 1, 3, 9, 10, 50, 65, 66, and 69 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) on the grounds of anticipation. Claims 1, 3-4, 7-11, 15, 20, 32, 36, 50, 54-57, 62, 65-67, and 69-70 are rejected under 35 U.S.C. 103 on the grounds of obviousness. Claims 1, 3-4, 7-11, 15, 20, 32, 36, 50, 54-57, 62, 65-67, and 69-70 are rejected on the grounds of nonstatutory double patenting.
Conclusion
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/BRENDAN P. OLISS/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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