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 .
Claim Status
Claims 2, 4, 5, 7, 17, 18, 25, 29, 35, 42, 54, 61, 64, 65, 113, and 125-129 are pending. Claim 129 is new. Claims 2, 4, 5, 7, 17, 25, 29, 35, 42, 54, 61, 64, 113, and 125-127 are currently amended. Claims 1, 3, 6, 8-16, 19-24, 26-28, 30-34, 36-41, 43-54, 55-60, 62-63, 66-112, 114-124 are cancelled.
Priority
The instant application is a CON of PCT/US2022/016023, filed 2/10/2022, which claims priority to the provisional applications 63/245,769, filed 9/17/2021, and 63/148,320, 2/11/2021. The priority date of 2/11/2021 is acknowledged.
Information Disclosure Statement
The IDS filed on 3/13/2024 is being considered.
Drawings
The drawings are objected to because 1) Figures 3 and 4 are blurry, 2) Figures 6-12, the Y axis is blurry and the grayscale makes it hard to determine which bars correspond to which antibiotics, 3) Figure 20, the graphs are too small to distinguish one isolate from another, 4) Figure 21 the axes as well as the legends with the symbols indicating which cohort is which are too small to read, 5) Figures 22 – 26, the symbols in the legend and on the graphs are too light in color to read, 6) Figure 27, 28, 29B, and 30-33 the legends are too small to read and there are no units on the Y axis, 7) Figure 29 the legend is too small to read, and 8) Figures 34 and 35 the x and y axes are too small to read.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 – 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.
Several paragraphs of the specification include sequences without SEQ ID NO’s – see [0007, 0133, 0134, 0135, 0203, and 0204].
Specification
The disclosure is objected to because of the following informalities: Tables 3-11 as well as those found in paragraphs 0477, 0478, 0479, 0481, 0483, 0484, 0486, 0487, 0508, 0515, 0516, 0519, 0520 are illegible. Appropriate correction is required.
Claim Objections
Claims 2 and 17 are objected to because of the following informalities:
Claim 2 – there is an extra space between “48 hr” and “, thereby treating” in line 3.
Line 6 also recites “a peptide… having a 70% to 100%” (emphasis added). Remove “a” such that the line reads “a peptide… having 70% to 100%” for improved clarity.
Claim 17 – there is an extra space between “dose that” and “is about” in line 2.
Line 2 also recites “at a dose is administered at as a unit dose” (emphasis added). Remove the second, emphasized “at” such that the claim reads “at a dose is administered as a unit dose” for improved clarity.
Appropriate correction is required.
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.
Claims 4 and 5 are 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.
Claims 4 and 5 both ultimately depend from claim 1, which is cancelled. For purposes of examination, claims 4 and 5 are being interpreted as if depending from claim 2.
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.
First rejection – written description
Claims 2, 4, 5, 7, 17, 18, 25, 29, 35, 42, 54, 61, 64, 65 and 125-129 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.
The claims are drawn to a method of treating or preventing a condition or disease in a human subject comprising intravenously administering a pharmaceutical composition comprised of a peptide with 70-100% sequence identity to SEQ ID NO: 1 and a pharmaceutically acceptable excipient; SEQ ID NO: 1 is the antimicrobial peptide WLBU2 (see, for example, SEQ ID NO: 10 in Figure 2 of Montelaro et al. (US 2003/0036627 A1, published 2/20/2003), which is 100% identical to the instant SEQ ID NO: 1). The claims broadly encompass the treatment or prevention of any condition or any disease by any peptide with at least 70% sequence identity to SEQ ID NO: 1. Therefore, the limitation “treating or preventing a condition or disease in a human subject” does not disclose sufficient structure-function relationship to meet the written description requirement.
The instant specification teaches that SEQ ID NO: 1 can be used to disrupt the integrity of a membrane by (a) binding to a negatively charged surface on a membrane; and/or (b) integrating into a membrane. The ability of a peptide to bind to a negatively charged surface on a membrane and/or integrate into a membrane can allow a peptide to act as a toxic agent to cells with a negatively charged surface by disrupting membrane integrity ([0053]).
The prior art indicates that a common mechanism underlying antimicrobial peptide specificity for bacterial and/or cancer cells is their attraction to the negatively charged plasma membranes of these cells. For instance, Montelaro (US 2003/0036627 A1, published 2/20/2003) teaches that the mechanisms by which peptides such as the instant SEQ ID NO: 1/WLBU2 kill bacteria proceeds in a two-step process by first binding to the negatively charged bacterial surface and driving these bound peptides into bacterial membranes, thereby disrupting its structural integrity. Similarly, Chen et al. (Targeting Negative Surface Charges of Cancer Cells by Multifunctional Nanoprobes. Theranostics. 2016 Aug 7;6(11):1887-98.) teach that cancer cells, relative to noncancerous cells, also similarly display negatively charged cell surfaces (Figure 5; “Interaction of the NPs with cancer cells” Pg 1892-1894).
Thus, while there is support for a common mechanism of action that peptides with 100% sequence identity to the instant SEQ ID NO: 1 may exhibit to target these cell populations in a method of treating, not all conditions or diseased are known to be associated with negatively charged plasma membranes.
In addition to the breadth of the conditions and/or diseases and whether the mechanism underlying the ability of SEQ ID NO: 1 to target bacterial and cancer cell populations can be extended to any/all cells of a condition or disease, there is also a question of whether any peptide with 70% or more sequence identity to the instant SEQ ID NO: 1 will maintain such a mechanism and effectively target said conditions or disease. Kelly et al. (US 20060058228, published 3/16/2006) discuss a phage display screen to identify peptides that distinguish between well-differentiated (HCT116) and poorly-differentiated (HT29) colon cancer cell lines. Analysis of the selected library resulted in the identification of a nine amino acid, disulfide-constrained peptide having a three amino acid (arg-pro-met, “RPM”) motif that specifically binds HT29 cells ([0032]). Substituting each of RPM with alanine significantly limited or abolished the ability of the peptide to compete with wild type RPM in a binding assay, indicating that these three residues alone accounted for the ability to bind to HT29 cells ([0034]). In contrast to this example, it is unknown which residues of a peptide with 70-100% sequence identity to SEQ ID NO: 1 would interact with or engage the appropriate cells and/or their machinery to successfully treat a condition or disease. Thus, one cannot extrapolate how a peptide with 70-100% sequence identity to SEQ ID NO: 1 might impact its functionality in a method of treatment.
Further, Guo (H.H. Guo, J. Choe, & L.A. Loeb, Protein tolerance to random amino acid change, Proc. Natl. Acad. Sci. U.S.A. 101 (25) 9205-9210, (2004).) teaches that a protein’s tolerance to random substitutions ultimately depends on whether the residues at hand are involved the protein’s functional activity. For instance, regions that were highly substitutable in the human DNA repair enzyme 3-methyladenine DNA glycosylase (AAG) include the first 79 N-terminal residues previously demonstrated to be unnecessary for in vitro enzyme activity and DNA binding specificity. In contrast, residues that are involved in glycosylase function or DNA binding did not tolerate amino acid substitutions (“Substitutability and Structure”, Pg 9207-9209; Figure 1). Figure 1 of Guo also indicates that tolerated substitutions are generally conservative, i.e., a nonpolar residue is substituted for another nonpolar residue, etc. However, there are no explicit limitations in the instant claims regarding the type of substitutions that can be made relative to SEQ ID NO: 1.
SEQ ID NO: 1 is 24 amino acids in length; sequences having at least 70% sequence identity would require 17 of the amino acids to be maintained (i.e. 17/24*100 = 70.83%) and would allow up to 7 amino acids (i.e. 24-17 = 7) to be substituted. Consequently, there are more than 3.46*106 possible ways to select up to 7 residues from the 24 residues in the sequence that are free to be modified (i.e. x = n!/(r!(n-r)!)); each of which could be substituted with any of the other 19 naturally occurring common amino acids (i.e., that number multiplied by 19). However, these variants do not take into consideration additional limitations one might consider with regards to the overall charge and structure of the peptide; because it is known that SEQ ID NO: 1 exerts its therapeutic impacts through interacting with and/or inserting itself into negatively charged membranes, one skilled in the art would additionally want to consider how to maintain the peptides alpha-helical structure as well as its overall positive charge, aspects which may not be conserved in a peptide with only 70% sequence identity to SEQ ID NO: 1.
Consequently, it is unknown whether all variants encompassed within the range of 70% sequence identity to SEQ ID NO: 1 would retain the structural, chemical, and/or physical properties required to engage negatively charged cell membranes to effectively treat or prevent any/all conditions or diseases. Therefore, the instant specification does not provide adequate written description to possess the broad genus described above since the specification does not disclose a correlation between the necessary structure of the sequence and the claimed function to be maintained.
Second rejection – scope of enablement
Claims 2, 4, 5, 7, 17, 18, 25, 29, 35, 42, 54, 61, 64, 65, 113, and 125-129 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 treating a condition or disease, does not reasonably provide enablement for preventing a condition or disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
1) Nature of the invention and 5) breadth of the claims: The claims are drawn to a
method of treating or preventing a condition or disease in a human through administering a peptide with 70-100% identity to SEQ ID NO: 1, which is a known antimicrobial peptide. The instant specification teaches administration of SEQ ID NO: 1 to treat microbial, viral, and fungal infections as well as some cancer species (see instant [0005, 0064, 0298-0307]; Examples 6 and 7; Figures 17-19).
However, prevention as claimed reads on administering SEQ ID NO: 1 to any individual with or without any condition or disease. Essentially, the claims read on administering a peptide with 70-100% identity to SEQ ID NO: 1 to anyone as a means of prevention.
2) State of the prior art and 4) predictability or unpredictability of the art: The state of the art at the time of filing did not recognize that peptide therapeutics such as a peptide with 70-100% sequence identity to SEQ ID NO: 1 could prevent a wide array of conditions or diseases. For instance, while Applicants are enabled for treating a subset of cancers (see instant [0243] and art rejections below), the art does not recognize that cancer can be prevented, let alone with a peptide therapeutic such as the instant SEQ ID NO: 1. There are several examples, discussed below, that suggest that therapeutic prevention might be possible someday but is presently not an option.
One such example is Cuzick et al. (Overview of the main outcomes in breast-cancer prevention trials. Lancet. 2003 Jan 25;361(9354):296-300.). Cuzick teaches that tamoxifen can reduce the risk of ER-positive breast cancer. However, Cuzick does not recommend tamoxifen as a preventive agent because continued research into specific subgroups of high-risk but healthy women is first needed (Pg 299, second column, first paragraph).
As another example, Schiffman et al. teach that primary prevention through vaccination against HPV might be possible in young women (The promise of global cervical-cancer prevention. N Engl J Med. 2005 Nov 17;353(20):2101-4.; Pg 2101, third column, first paragraph). However, they also teach that vaccine evaluations are ongoing (Pg 2103, third column, first paragraph). In addition, the most promising vaccines designed against HPV types 16 and 18 would only prevent 70 percent of cervical cancer cases at best (Pg 2103, second column, first paragraph). Therefore, there is still no vaccine that can definitively prevent cancer.
Other promising candidates for cancer prevention include tumor-associated antigen vaccines (Evans TR, Kaye SB. Vaccine therapy for cancer--fact or fiction? QJM. 1999 Jun;92(6):299-307.) and lunasin, a soy-derived peptide (Hernández-Ledesma B, Hsieh CC, de Lumen BO. Lunasin, a novel seed peptide for cancer prevention. Peptides. 2009 Feb;30(2):426-30.; Abstract.). However, in each of these studies, the authors indicate that additional research is required before such they can be greenlit as preventative therapeutics.
Thus, one skilled in the art would reasonably predict that a composition comprising a peptide with 70-100% sequence identity to the instant SEQ ID NO: 1 would not be able to prevent cancer.
Also, one would predict that a peptide with 70-100% sequence identity to the instant SEQ ID NO: 1 would not be able to prevent a microbial infection either. A peptide would need to interact directly with said microbe in order to exert its therapeutic impact; however, in order for said peptide, administered to a human subject, to interact with said microbe, the human subject would have to already be infected, in which case prevention would not be possible.
3) The relative skill of those in the art: The relative skill of those in the art is high.
6) The amount of direction or guidance presented: At the time of filing, no direction or
guidance was presented in either the prior art or the instant specification that would enable one to administer a peptide with 70-100% identity to SEQ ID NO: 1 to prevent a condition or disease as claimed.
7) The presence or absence of working examples: The instant specification provides no
examples wherein SEQ ID NO: 1 is administered prior to the onset of a condition or a disease.
8) The quantity of experimentation necessary: As there are no working examples in
either the instant specification nor the prior art, reasonable guidance with respect to preventing a condition or disease through administration of a peptide with 70-100% sequence identity to SEQ ID NO: 1 was limited. Consequently, one skilled in the art would be burdened with undue experimentation to determine the precise parameters and conditions necessary to effectively prevent a condition or disease.
Therefore, in view of the Wands factors, as discussed above, Applicants fail to provide information sufficient to practice the claimed invention for the prevention of a condition or disease.
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.
Claim(s) 2, 17, 18, 113, and 127 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Deslouches et al. (US20200079827A1, published 3/12/2020).
Deslouches teaches compositions comprised of antimicrobial peptides (AMPs) as well as methods of treating microbial infections, reducing biofilms, decreasing inflammation, and treating infectious disease in a subject in need thereof comprising administering to the subject a therapeutic amount of an antimicrobial peptide (Abstract). Methods of treating cancer are also contemplated ([0012]).
Deslouches teaches the peptide SEQ ID NO: 26/WLBU2, which is 100% identical to the instant SEQ ID NO: 1. Deslouches also teaches SEQ ID NO: 32 and 33 which exhibit 84.6% and 76.9% sequence identity to the instant SEQ ID NO: 1, respectively (Sequence Listing). The AMP may be in a pharmaceutical composition further comprising a pharmaceutically acceptable excipient ([0089]).
Deslouches teaches administration of AMPs by infusion (intravenous) which can occur over a period of about 15 minutes to 24 hours ([0104]). Thus, claim 2 is anticipated.
Deslouches teaches administration of the AMP in about 1mg/kg to about 150mg/kg ([0093, 0095]). Thus, claims 17 and 18 are anticipated.
Deslouches teaches treating infections (Abstract; [0005, 0074]). Thus, claim 113 is anticipated.
Deslouches teaches that the composition can take forms such as suspensions, solutions or emulsions in oily or aqueous vehicles (aqueous carrier) ([0104]). Thus, claim 127 is anticipated.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 2, 7, 17, 18, 25, 29, 35, 42, 54, 61, 64, 65, 113, 127, and 129 are rejected under 35 U.S.C. 103 as being unpatentable over Steckbeck et al. (WO 2019178274 A1, published 9/19/2019) in view of Deslouches et al. (US20200079827A1, published 3/12/2020).
Steckbeck teaches peptides with antimicrobial, antiviral, antifungal, and antitumor activity administered to subjects (Abstract). Steckbeck teaches the peptide SEQ ID NO: 1, which is 100% identical to the instant SEQ ID NO: 1.
Steckbeck further teaches administering pharmaceutical compositions containing SEQ ID NO: 1 to a subject in need thereof ([0003]). The pharmaceutical composition can be administered intravenously ([0161]). The pharmaceutical composition can be formulated for administration to a subject in order to treat a disease or condition ([0034]). The pharmaceutical formulations can comprise a peptide of the invention (SEQ ID NO: 1) and at least one of an excipient, diluent, or a carrier ([0004, 0005, 0124-0129]).
Steckbeck does not teach intravenously administering said pharmaceutical composition comprising a peptide having 70-100% sequence identity to the instant SEQ ID NO: 1 over a period of about 1 to about 48 hours.
Deslouches teaches administration of compositions comprising antimicrobial peptides such as SEQ ID NO: 26, 32, and 33, which exhibit >70-100% sequence identity to the instant SEQ ID NO: 1 and a pharmaceutically acceptable excipient ([0089]). Deslouches teaches administration of AMPs by infusion (intravenous) can occur over a period of about 15 minutes to 24 hours ([0104]).
In summary, Steckbeck teaches a method of treating microbial infections or certain cancers comprising administering a peptide with 100% sequence identity to the instant SEQ ID NO: 1. Deslouches teaches a method of treating a microbial infections or certain cancers comprising intravenous administration of a peptide with ~70-100% sequence identity to the instant SEQ ID NO: 1 for 15 minutes – 24 hours.
Thus, regarding claim 2, it would be prima facie obvious to incorporate the time of administration taught by Deslouches into the method of Steckbeck. One skilled in the art would be motivated to do so as both Steckbeck and Deslouches are drawn to similar methods of treating similar diseases (infections and cancer) using similar AMPs. Moreover, one would have a reasonable expectation of success given that peptides with ~70-100% sequence identity to the instant SEQ ID NO: 1 are known to effectively treat microbial infections and some cancers, as taught by Deslouches.
Regarding claim 7, Deslouches teaches that intravenous administration occurs from a time period of 15 minutes – 24 hours ([0104]).
Regarding claims 17 and 18, Deslouches teaches administration of the AMP in about 1mg/kg to about 150mg/kg ([0093, 0095]).
Regarding claims 25 and 29, Steckbeck teaches the peptide or pharmaceutically acceptable salt thereof can have a half-life from about 1 minute to 600 minutes (10 hours).
Regarding claims 35 and 42, Steckbeck teaches that the maximum observed plasma concentration (Cmax) of the peptide or pharmaceutically acceptable salt thereof can be from about 50ng/mL to about 1000ng/mL ([0194]).
Regarding claims 54 and 61, Steckbeck teaches that the AUC(O-t) of said peptide or pharmaceutically acceptable salt thereof ranges from about 1900ng*h/mL – 10000ng*h/mL, wherein t is 90 hours after administration, wherein t=90.
Regarding claims 64 and 65, Steckbeck teaches the Tmax of a peptide or pharmaceutically acceptable salt thereof is about 1m to 600m (10h) ([0192]).
Regarding claims 113, Steckbeck teaches treating an infection such as a bacterial infection or infections in the urinary tract, abdomen, blood stream, or periprosthetic joint (Abstract; [0002]). Deslouches also teaches treating infections (Abstract; [0005, 0074]).
Regarding claim 127, Deslouches teaches that the composition can take forms such as suspensions, solutions or emulsions in oily or aqueous vehicles (aqueous carrier) ([0104]).
Regarding claim 129, Steckbeck teaches SEQ ID NO: 1 which is 100% identical to the instant SEQ ID NO: 1.
Claim(s) 2, 4, 5, 7, 17, 18, 25, 29, 35, 42, 54, 61, 64, 65, 113, 127, and 129 are rejected under 35 U.S.C. 103 as being unpatentable over Steckbeck et al. (WO 2019178274 A1, published 9/19/2019) and Deslouches et al. (US20200079827A1, published 3/12/2020), as applied to claims 2, 7, 17, 18, 25, 29, 35, 42, 54, 61, 64, 65, 113, 127, and 129 above, and further in view of Rombouts et al. (Systematic Review on Infusion Reactions to and Infusion Rate of Monoclonal Antibodies Used in Cancer Treatment. Anticancer Res. 2020 Mar;40(3):1201-1218.).
The teachings of Steckbeck and Deslouches have been set forth above. Steckbeck and Deslouches do not teach a method wherein by treating a condition or disease it also reduces an infusion related reaction, its severity, or combination thereof, relative to administering otherwise said same pharmaceutical composition over a time period of about 5-30 minutes.
Rombouts teaches that treating cancer patients with monoclonal antibodies can result in complications, particularly the occurrence of infusion-related reactions. Mild to moderate reactions are associated with chills, fever, mild hypotension, dyspnea and rash, and more severe symptoms can also occur. Most infusion reactions occur within 30minutes to 2 hours after the start of administration (Pg 1201, first column, paragraph after Abstract – second column, first paragraph).
In summary, Steckbeck and Deslouches teach a method of treating cancer through intravenously administering a pharmaceutical composition comprising the instant SEQ ID NO: 1 and a pharmaceutically acceptable excipient. Rombouts teaches treating cancer through intravenous administration of monoclonal antibodies, which sometimes causes infusion related reactions within 30 minutes-2 hours of administration.
Per MPEP 2144.06(I), combining equivalents known for the same purpose is one legal precedent recognized by the courts as directed to common practices that normally require only ordinary skill in the art and are considered routine expedients: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
By extension of this, it would be obvious to combine the method of treating cancer taught by Steckbeck and Deslouches and the method of treating cancer taught by Rombouts because both method methods effectively treat cancer. Additionally, one skilled in the art would recognize that combining the treatment of Steckbeck and Deslouches with that of Rombouts would allow one to effectively treat cancer as well as any possible infusion related reactions simultaneously because the time period during which most infusion related reactions occur (30 minutes – 2 hours) overlaps with the time period during which SEQ ID NO: 1 and monoclonal antibodies are administered (15 min – 24 hours). Thus, claims 4 and 5 are rendered obvious.
Claim(s) 2, 7, 17, 18, 25, 29, 35, 42, 54, 61, 64, 65, 113, and 125-129 are rejected under 35 U.S.C. 103 as being unpatentable Steckbeck et al. (WO 2019178274 A1, published 9/19/2019) and over Deslouches et al. (US20200079827A1, published 3/12/2020), as applied to claims 2, 7, 17, 18, 25, 29, 35, 42, 54, 61, 64, 65, 113, 127, and 129 above, and further in view of Lebowitz et al. (The pH and acidity of intravenous infusion solutions. JAMA. 1971 Mar 22;215(12):1937-40.).
The teachings of Steckbeck and Deslouches have been set forth above. Steckbeck and Deslouches do not teach the that the pharmaceutical formulation has a pH of about 4-9.
Lebowitz teaches that typical intravenous infusion solutions have pH values ranging from 4.2 to 7.1 (Abstract; Pg 1937, first column, first paragraph).
Thus, regarding claims 125 and 126, Steckbeck and Deslouches teach a method of treating an infection or cancer through intravenously administering a pharmaceutical composition comprising the instant SEQ ID NO: 1 and a pharmaceutically acceptable excipient. Lebowitz teaches that intravenous infusion solutions typically have a pH of 4.2-7.1. Based on these teachings, it would be obvious to formulate the pharmaceutical composition of Steckbeck and Deslouches with a pH of 4.2-7.1. One skilled in the art would be motivated to do so because Leibowitz taught that this pH range is what is typically administering to patients who receive intravenous infusions. One would have a reasonable expectation of success as Lebowitz taught that this is the standard for intravenous infusions.
Regarding claims 127 and 128, the instant specification teaches that an aqueous carrier can be lactated Ringer’s solution or normal saline (0.9% w/v) ([0161]). Leibowitz teaches lactated Ringer’s solution as well as normal saline (0.9% w/v; Pg 1, middle column, “Method” and Tables 2 and 3).
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 2, 125-127, and 129 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-7, and 14-15 of copending Application No. 19/072,538 (‘538; claim set filed 5/13/2025).
Claim 1 of copending Application No. ‘538 recites a pharmaceutical formulation comprising (a) a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% identity to a polypeptide sequence of SEQ ID NO: 1 or 15-25 and (b) at least one pharmaceutically acceptable excipient; wherein the pharmaceutical formulation has a pH of about 3.5 to 5.5; and wherein the pharmaceutical formulation comprise at most 5% by weight of at least one impurity as measured when stored for at least 50 days at 40°C. SEQ ID NO: 1 of copending Application No. ‘538 and the instant SEQ ID NO: 1 are 100% identical. The instant specification of copending Application No. ‘538 teaches that SEQ ID NO: 1 can be used to treat a disease or condition ([0088]), and the pharmaceutical formulation can be formulated for intravenous administration ([0076]).
Dependent claims include specific pH values of the pharmaceutical formulation (claims 5-7) and species of the peptide (claims 14-15).
This is a provisional nonstatutory double patenting rejection.
Claims 2, 125-127, and 129 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 19, 38, 40, and 54 of copending Application No. 18/606,023 (‘023; claim set filed 11/22/2024).
Claim 1 of copending Application No. ‘023 recites a pharmaceutical formulation comprising: (a) a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of SEQ ID NO: 1 or 15-25 or any combination thereof and (b) aqueous sodium bicarbonate at a concentration from about 50mM to about 300 mM. A method of making a pharmaceutical formula thereof from a kit is also recited in claim 38.
SEQ ID NO: 1 of copending Application No. ‘023 and the instant SEQ ID NO: 1 are 100% identical. The instant specification of copending Application No. ‘023 teaches that SEQ ID NO: 1 can be used to treat a disease or condition ([00124]), and the pharmaceutical formulation can be formulated for intravenous administration ([00129]).
Dependent claims include specific pH values of the pharmaceutical formulation (claims 3 and 40) and species of the peptide (claims 19 and 54).
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658