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 .
Election/Restrictions
Applicants’ election without traverse of Group I (i.e., claims 1, 3, 7, 11, 13 and 22) in the reply filed on 08/07/2026 is acknowledged. Applicants’ election without traverse of Species A (i.e., SEQ ID NO: 1) in the reply filed on 08/07/2026 is acknowledged.
Claims 56, 69-70, 95 and 97-102 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/07/2026.
Priority
The present application claims the benefit under 35 U.S.C 119 (e) to U.S. Provisional Application No. 63/245,774 filed 09/17/2021. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C 119 (e) or under 35 U.S.C 120, 121, or 365 (c ) is acknowledged. And also claims status as a 371 (National Stage) of PCT/US2022/076560 filed 09/16/2022.
Claim Status
Claims 1-94 were originally filed on 03/15/2024.
The amendment filed on 11/22/2024 cancelled claims 2, 4-6, 8-10, 12, 14-18, 21, 23-37, 39, 41-42, 44-50, 57-67, 71-94; added new claims 95-96; and amended claims 1, 3, 7, 11, 19-20, 22, 38, 40, 43, 51-55, 69-70.
The amendment filed on 08/07/2026 cancelled claim 19-20, 38, 40, 43, 51-55, 68 and 96; added new claims 97-102; and amended claims 1, 3, 7, 11, 13, 22, 56.
Claims 1, 3, 7, 11, 13, 22, 56, 69-70, 95 and 97-102 are currently pending, and claims 1, 3, 7, 11, 13, 22 are under examination.
Information Disclosure Statement
The IDS filed on 09/23/2024 has been considered by the Examiner.
Claim Objections
Claim 13 is objected to because of the following informalities: grammar. The claim recites “at a concentration at about 12.6mg/mL”. The preposition “at” should be replaced by the preposition “of” Appropriate correction is required.
Claim 22 is objected to because of the following informalities: grammar. The claim recites “a bacterial burden a greater extent”. The preposition “to” should be included between the noun “burden” and the phrase “a greater extent”. Appropriate correction is required.
Claim Interpretation
The scope of “a peptide with a polypeptide sequence of SEQ ID NO: 1” is interpreted as open-ended requiring 100% identity with SEQ ID NO: 1 with any N-/-C terminal additions.
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.
1. Claim 22 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.
Claim 22 recites the limitation "synergistic effect with the peptide " in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. Claim 22 depends from parent claim 1, which includes a pharmaceutically acceptable salt of a peptide with a polypeptide of SEQ ID NO: 1. Therefore, the limitation “synergistic effect with the peptide” lacks antecedent basis because claim 1 only includes recitation of a pharmaceutically acceptable salt of a peptide with a polypeptide sequence of SEQ ID NO: 1. Claim 1 does not include the peptide as an alternative to the pharmaceutically acceptable salt of SEQ ID NO: 1.
2. Claim 22 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.
Claim 22 is indefinite because it includes a subjective term. The term “greater extent” fails to particularly point out and distinctly claim the degree of bacterial reduction exerted by the claimed irrigation solution, nor by each of the individual components of the claimed solution. Per MPEP 2173.05(b)(IV), [w]hen a subjective term is used in the claim, the examiner should determine whether the specification supplies some objective standard for measuring the scope of the term. Some objective standard must be provided in order to allow the public to determine the scope of the claim. A claim term that requires the exercise of subjective judgment without restriction may render the claim indefinite. In re Musgrave, 431 F.2d 882, 893, 167 USPQ 280, 289 (CCPA 1970). In the instant case, the specification is silent about an objective standard for measuring the scope of the term “to a greater extend”. Thus, an ordinary skilled artisan would not be able to ascertain the metes and bounds of the claimed invention with respect to the scope of the synergistic effect the aqueous sodium bicarbonate with a pharmaceutically acceptable salt of SEQ ID NO: 1, nor the effect of administering the individual components of the claimed irrigation solution.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness
(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
3. Claims 1, 3, 7, 11, 13 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Mandell et al., J Orthop Res. 2020; 28:2657-2663 (cited in the IDS filed on 09/23/2024) (herein after “Mandell”); in view of Swedan et al., Infection and Drug Resistance. 2019:12; 2019-2030 (cited in the IDS filed on 09/23/2024) (herein after “Swedan”); and US 10,940,163 B2 Date of Patent: Mar. 9, 2021 (herein after “Brown”).
Regarding claim 1, Mandell teaches WLBU2 dissolved in differing irrigation solvents, such as diphosphate buffered saline (dPBS) (see pg. 2657, abstract). WLBU2 is a de nova-engineered cationic peptide inspired by the optimization of cationic helical amphipathic structures of the intracellular motifs (lentivirus lytic peptides) observed in the transmembrane protein gp41 of the human immunodeficiency virus-1 (see pg. 2658, left column, paragraph 2). WLBU2 has been demonstrated to eliminate biofilms and create culture negative implants within 30 minutes; thereby potential indications of its use include intraoperative delivery for irrigation and debridement in periprosthetic joint infection (PJI) based on its ability to rapidly eliminate antibiotic tolerant biofilm from implant surfaces (see pg. 2658, left column, paragraph 2).Additionally, Mandell teaches that WLBU2 activity was increased in alkaline dPBS and that when WLBU2 was dissolved in less acidic dPBS, it displayed increased efficacy in treating PJI implants ex vivo (see pg. 2657, abstract).
Mandell adds that the activity of cationic peptides are dependent on ionic strength and pH; and that typical irrigation solutions utilized in the lavage of surgical wounds include normal saline or lactated ringers solution (see pg. 2658, left column, last paragraph). Mandell also teaches that infected implant pieces were tested with WLBU2 at both 0.5 and 1.0 mg/mL in PBS adjusted to pH of 6.5, 6.8, 7.0, 7.2, 7.4, and 8.0 (see pg. 2658, right column, second paragraph). For ionic strength analysis, dPBS was adjusted to hypertonic conditions by addition of NaCl to dPBS (0.3 M) and hypotonic conditions by addition of deionized water to dPBS (0.08 M) (see pg. 2658, right column, second paragraph).
MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art", a prima facie case of obviousness exists. Therefore, the claimed concentration range of the peptide would have been obvious to one of ordinary skill in the art since the prior art range (i.e., 0.5 and 1.0 mg/mL) lies within the claimed concentration range (i.e., from 1mg/mL to 10mg/mL).
Thus, Mandell’s teachings read on an irrigation solution comprising (a) sterile water, and wherein the concentration of the peptide is from 1mg/mL to 10 mg/mL as recited in instant claim 1. However, Mandell does not expressly teach (b) the pharmaceutically acceptable salt of a peptide with a polypeptide sequence of Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1); and aqueous sodium bicarbonate at a concentration from about 50mM to about 300 mM.
Swedan reports synergism of cationic antimicrobial peptide WLBU2 with antibacterial agents against biofilms of multi-drug resistant Acinetobacter baumannii and Klebsiella pneumoniae (see pg. 2020, Title). Swedan teaches that WLBU2 is a peptide consisting of 24-amino acid residues, and the amino acid sequence is RRWVRRVRRWVRRVVRVVRRWVRR (see pg. 2021, left column, first paragraph). It is noted that Swedan’s WLBU2 sequence is 100% identical to instant SEQ ID NO: 1. Swedan adds that the synthesis of the peptide was based on the solid phase method and standard Fmoc chemistry (see pg. 2021, left column, first paragraph). Swedan’s teachings pertaining to the solid phase method and standard Fmoc chemistry are being interpreted as the preparation of a pharmaceutically acceptable salt of the cationic antimicrobial peptide WLBU2. Thereby Swedan’s teachings read on a pharmaceutically acceptable salt of a peptide with a polypeptide sequence of SEQ ID NO: 1, as recited in instant claim 1.
With respect to (c) aqueous sodium bicarbonate at a concentration from about 50mM to about 300 mM:
Brown’s invention pertains to bicarbonate as a potentiator for antimicrobial agents (see front pg. Title). Brown teaches that bicarbonate is present in all body fluids and organs and plays a critical role in maintaining acid-base balance in the human body (see column 52, lines 45-47). Brown claims an antimicrobial composition comprising an effective amount of (i) bicarbonate and (ii) an antimicrobial agent; wherein the bicarbonate is present in the composition at a concentration of about 20 mM to about 100 mM (see column 54, claim 1). Brown also teaches that in some embodiments the antimicrobial agent is a cationic antimicrobial agent (see column 10, lines 5-6).
Pursuant to MPEP 2144.05(I) "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art", a prima facie case of obviousness exists. Therefore, the claimed range concentration of the aqueous sodium bicarbonate would have been obvious to one of ordinary skill in the art since the prior art sodium bicarbonate concentration range (i.e., about 20 mM to about 100mM) lies within the claimed concentration range (i.e., from about 50 mM to about 300mM).
Brown studied the bacteriostatic mechanism of bicarbonate and its interaction with antimicrobial agents of varying mechanisms of action (see column 52, lines 47-50). All interactions pointed to a mechanism whereby the bicarbonate ion causes perturbation of the pH gradient of proton motive force (PMF) across the cytoplasmic membrane (see column 52, lines 53-55). Thus, by altering the cell's transmembrane pH gradient, bicarbonate potentiates antibiotic activity by increasing the effective intracellular levels of various antibiotics or enhancing their ability to collapse PMF (see column 53, lines 21-25).
From the teachings of the references, the Examiner recognizes that it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Mandell, Swedan, and Brown to arrive at the claimed irrigation solution comprising (a) sterile water, (b) a pharmaceutically acceptable salt of a peptide with a polypeptide sequence of SEQ ID NO: 1, wherein the concentration of the pharmaceutically acceptable salt of the peptide is from 1mg/mL to 10mg/mL, and (c) aqueous sodium bicarbonate at a concentration from about 50 mM to about 300 mM.
One of ordinary skill in the art would have been motivated to do so because it was known that:
the cationic peptide WLBU2 has demonstrated to rapidly eliminate antibiotic tolerant biofilm from implant surfaces, thereby its application includes intraoperative delivery for irrigation and debridement in periprosthetic joint infection, as taught by Mandell; WLBU2 is a peptide consisting of 24-amino acid residues, and the amino acid sequence is RRWVRRVRRWVRRVVRVVRRWVRR and has demonstrated synergism with antibacterial agents, as taught by Swedan; and because bicarbonate alters the cell’s transmembrane pH gradient, thereby potentiating antibiotic activity by increasing the effective intracellular levels of various antibiotics or enhancing their ability to collapse PMF (proton motive force), as taught by Brown.
One of ordinary skill in the art would have had a reasonable expectation of success in achieving the claimed irrigation solution given that: WLBU2 activity was increased when dissolved in alkaline dPBS and when dissolved in less acidic dPBS it displayed increased efficacy in treating PJI implants ex vivo, taught by Mandell; and given that the bacteriostatic mechanisms of bicarbonate and its interaction with antimicrobial agents of varying mechanisms of action had been previously studied and resulted in the bicarbonate ion causing perturbation of the pH gradient of proton motive force (PMF) across the cytoplasmic membrane thereby potentiating or enhancing the activity of the antimicrobial agent. Since all the claimed elements were known in the prior art one skilled in the art would have combined the elements as claimed by known methods with no change in the respective functions (i.e., cationic antimicrobial peptide and antimicrobial agent potentiator/enhancer) and the combination would have yielded predictable results (i.e., irrigation solution).
As such, the combined teachings of Mandell, Swedan, and Brown would support the instantly claimed irrigation solution by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention; and/or combining prior art elements according to known methods to yield predictable results; and/or the use of a known technique to improve similar devices (methods, or products) in the same way; pursuant to KSR.
Regarding claims 3 and 7, as previously mentioned, Mandell teaches dissolving 1.0mg/mL of WLBU2 in PBS adjusted to pH of 6.5, 6.8, 7.0, 7.2, 7.4, and 8.0 (see pg. 2658, right column, second paragraph). Per MPEP 2144.05(I), "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art", a prima facie case of obviousness exists. Therefore, the claimed pH range of the irrigation solution would have been obvious to one of ordinary skill in the art since the prior art range (i.e., pH 6.5, 6.8, 7.0, 7.2, 7.4, and 8.0) lies within the claimed concentration range (i.e., from about 7 to about 11). Similarly, the claimed concentration range of the peptide would have been obvious to one of ordinary skill in the art since the prior art range (i.e., 0.5 and 1.0 mg/mL) lies within the claimed concentration range (i.e., about 1mg/mL, about 3mg/mL, about 5mg/mL, or about 10mg/mL). Thus, Mandell’s teachings read on the claim limitations recited in instant claims 3 and 7.
Regarding claims 11 and 13, Brown teaches that in some embodiments, the concentration of bicarbonate is about 150mM (see column 31, lines 15 and 18).
With respect to the presence of sodium bicarbonate in the irrigation solution at a concentration of about 12.6 mg/mL; the conversion of millimolar (i.e., mM) to milligrams per milliliter (mg/mL) can be achieved by multiplying the concentration of sodium bicarbonate in mM by 0.084 mg/mL of sodium bicarbonate (i.e., 150mM multiplied by 0.084mg/mL), which is equivalent to 12.6 mg/mL. Thus, the teachings of Brown read on a sodium bicarbonate concentration of about 150mM, as recited in instant claim 7; and a sodium bicarbonate concentration of about 12.6mg/mL, as recited in instant claim 13.
Regarding claim 22, Swedan teaches synergism of cationic antimicrobial peptide WLBU2 with antibacterial agents against biofilms of multi-drug resistant Acinetobacter baumannii and Klebsiella pneumoniae (see Front pg., Title). Thus, the cationic antimicrobial peptide WLBU2 represented by amino acid sequence RRWVRRVRRWVRRVVRVVRRWVRR, in combination with antimicrobials holds promise in eradication of multi drug resistant pathogens (see Front pg., abstract).
Additionally, as taught in the literature reviewed by Brown; PMF, the product of cellular respiration, describes the electrochemical potential at the cytoplasmic membrane that is composed of an electrical potential (Δψ, negative inside) and a proton gradient (ΔpH, acidic outside). This electro-chemical potential crucially underpins energy production so that bacterial cells work to maintain a constant PMF (see column 52, lines 56-61). Agents that perturb either Δψ or ΔpH are growth inhibitory and prompt a compensatory increase in the other component in order to maintain PMF (see column 52, lines 63-65).
Further, synergy in growth inhibition is observed when an agent active on the electrical potential is combined with an agent that targets the proton gradient (see column 52, lines 65-68 to column 53, line 1). Thus, in dissipating the pH gradient, bicarbonate had enhancing effects on other antibacterial compound through distinct mechanisms. For instance, mechanism (a) bicarbonate dissipated the pH gradient across the cytoplasmic membrane and led to an increase in the compensatory component, the membrane potential (see column 53, lines 4-7). For antibiotics whose entries are dependent on the membrane potential, an enhancement of growth inhibition was observed in the presence of sodium bicarbonate consistent with an increase in antibiotic entry (see column 53, lines 7-10). Further, by disrupting the energetics across the membrane, bicarbonate also disrupts energy-dependent efflux thus potentiating the activity of efflux substrates (e.g. macrolides) (see column 53, lines 11-14). In these instances, it was observed that bicarbonate led to an increase in intracellular concentration of the antibiotic (see column 53, lines 15-16).Mechanism (b), bicarbonate enhanced those compounds that disrupt membrane potential component as a primary mechanism of action (see column 53, lines 17-19). These activities were potentiated via a synergistic collapse of both components of PMF, Δψ the antibiotic and ΔpH by bicarbonate (see column 53, lines 19-21).
Therefore, before the effective filing date of the claimed invention, an ordinary skilled artisan would have been motivated with reasonable expectation of success to incorporate a pharmaceutically acceptable salt of the cationic antimicrobial peptide WLBU2, and sodium bicarbonate in an irrigation solution because both components (i.e., WLBU and sodium bicarbonate), were individually known to elicit synergistic effects with antibacterial agents; and given that sodium bicarbonate was known to potentiate and/or enhance the activity of antibiotic agents when administered in combination therewith.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 U.S.C. 103. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references discussed above.
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.
4. Claims 1, 3, 7, 11, 13 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14-15 of copending Application No. 19/072,538 (reference application) PG Pub US20250195611A1, claim set filed 05/13/2025; in view US 10,940,163 B2 Date of Patent: Mar. 9, 2021 (herein after “Brown”) as evidenced by Swedan et al., Infection and Drug Resistance. 2019:12; 2019-2030 (cited in the IDS filed on 09/23/2024) (herein after “Swedan”).
Regarding instant claims 1,3, 7, 11, 13 and 22, Copending App ‘538 claims:
A pharmaceutical formulation comprising:
(a) a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of:Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1) […]; and
(b) at least one pharmaceutically acceptable excipient; wherein the pharmaceutical formulation has a pH of about 3.5 to about 5.5; and wherein the pharmaceutical formulation comprises at most 5% by weight of at least one impurity as measured by high-performance liquid chromatography (HPLC) when stored for at least 50 days at 40C (see Copending App ‘538, claim 1).
The pharmaceutical formulation of claim 1, wherein the peptide comprises at least about 90% sequence identity to a polypeptide sequence of: Arg-Arg-Trp-Val-Arg-Arg-Val- Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1) (see Copending App ‘538, claim 14).
The pharmaceutical formulation of claim 14, wherein the peptide comprises Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp- Val-Arg-Arg (SEQ ID NO: 1) (see Copending App ‘538, claim 15).
Brown teaches bicarbonate as a potentiator for antimicrobial agents and claims a composition comprising an effective amount of (i) bicarbonate, at a concentration of about 20 mM to about 100mM, and (ii) an antimicrobial agent (see Brown, Front pg. and column 54, claim 1). With respect to the claimed irrigation solution and the claimed synergistic effect of sodium bicarbonate with the peptide. MPEP 2112.01(II) states that "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. Id.
In the instant case, the claimed irrigation solution comprises a pharmaceutically acceptable salt of a peptide with a sequence of SEQ ID NO: 1, which is also known in the prior art as WLBU2 as taught by Swedan, and sodium bicarbonate. Before the effective filing date of the claimed invention, both WLBU and sodium bicarbonate were known to individually elicit a synergistic effect in the presence of other antimicrobial agents. Thus, it must naturally follow that the claimed irrigation solution comprising aqueous sodium bicarbonate provides a synergistic effect with the claimed pharmaceutically acceptable salt of the peptide represented by SEQ ID NO: 1. Since all the claimed elements were known in the prior art one skilled in the art would have combined the elements as claimed by known methods with no change in the respective functions (i.e., cationic antimicrobial peptide and antimicrobial agent potentiator/enhancer) and the combination would have yielded predictable results (i.e., irrigation solution).
The instant claims would have been obvious because the combination of known elements would have yielded predictable results to one of ordinary skill in the art at the time of the invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
5. Claims 1, 3, 7, 11, 13 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 21, 25, 28 of copending Application No. 18/290,214 (reference application) PG Pub US20240317809A1, claim set filed 05/26/2026; in view of US 10,940,163 B2 Date of Patent: Mar. 9, 2021 (herein after “Brown”).
Regarding instant claims 1, 11, 13 and 22, Copending App ‘214 claims:
A method for treating or preventing periprosthetic joint infection in a patient in need thereof, wherein a prosthetic joint is implanted in said patient; the method comprising administering:(i) a pharmaceutical composition comprising:(a) a peptide or pharmaceutically acceptable salt thereof, wherein said peptide has at least 90% sequence identity to a polypeptide sequence WLBU-2 (SEQ ID NO: 10); and(b) an aqueous carrier; wherein said pharmaceutical composition is in a form of a liquid, wherein said pharmaceutical composition is locally administered to said prosthetic joint in vivo; and(ii) an antibiotic or pharmaceutically acceptable salt thereof; and wherein administration of said pharmaceutical composition and said antibiotic reduces a bacterial burden of said periprosthetic joint infection to a greater extent as compared to administering (i) or (ii) alone (see Copending App ‘214, claim 1).
The method of claim 1, wherein said administering comprises irrigating said prosthetic joint with said pharmaceutical composition, wherein said prosthetic joint is exposed (see Copending App ‘214, claim 12).
The method of claim 1, wherein said peptide or pharmaceutically acceptable salt is WLBU-2 (SEQ ID NO: 10) (see Copending App ‘214, claim 21).
Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). This is pertinent because in Copending App ‘214, SEQ ID NO: 10 corresponds to RRWVRRVRRVWRRVVRVVRRWVRR. Thereby, instant SEQ ID NO: 1 and SEQ ID NO: 10 in copending App ‘214 are 100% identical.
Regarding instant claim 3, copending App ‘214 claims:
The method of claim 1, wherein said pharmaceutical composition comprises a pH value of from about 5 to about 10 (see copending App ‘214, claim 25).
Regarding instant claim 7, copending App ‘214 claims:
The method of claim 1, wherein said peptide or pharmaceutically acceptable salt thereof is present in said pharmaceutical composition at a concentration from at least about 1 mg/mL to at least about 10 mg/mL (see copending App ‘214, claim 28).
An ordinary skilled artisan would have been motivated with reasonable expectation of success to combine the claims of copending App ‘214 and the teachings of Brown to arrive at the claimed irrigation solution. Brown teaches bicarbonate as a potentiator for antimicrobial agents and claims a composition comprising an effective amount of (i) bicarbonate, at a concentration of about 20 mM to about 100mM, and (ii) an antimicrobial agent (see Brown, Front pg. and column 54, claim 1). Since all the claimed elements were known in the prior art one skilled in the art would have combined the elements as claimed in copending App ‘214 by known methods with no change in the respective functions (i.e., cationic antimicrobial peptide and antimicrobial agent potentiator/enhancer) and the combination would have yielded predictable results (i.e., irrigation solution). The instant claim would have been obvious because the combination of known elements would have yielded predictable results to one of ordinary skill in the art at the time of the invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending App ‘214 claims a method of treating a joint infection with an irrigation solution comprising SEQ ID NO: 10. Additionally, SEQ ID NO: 10 in Copending App ‘214 is 100% identical to instant SEQ ID NO: 1. The instant invention would have been obvious to an ordinary skilled artisan because copending App ‘214 is drawn to a method of treating by administering a pharmaceutical composition in a form of a liquid, therefore Copending App ‘214 encompasses a species of the instantly claimed irrigation solution. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
6. Claims 1, 3, 7, 11, 13 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of copending Application No. 18/447,414 (reference application) PG Pub US20240115654A1, claim set filed 06/26/2026; in view of US 10,940,163 B2 Date of Patent: Mar. 9, 2021 (herein after “Brown”) as evidenced by Swedan et al., Infection and Drug Resistance. 2019:12; 2019-2030 (cited in the IDS filed on 09/23/2024) (herein after “Swedan”).
Regarding instant claims 1, 3, 7, 11, 13 and 22, Copending App ‘414 claims:
A method of treating a condition or disease in a human subject in need thereof comprising intravenously administering a pharmaceutical composition to said human subject over a time period of from about 1 hr. to about 48 hr., thereby treating the condition or disease in said human subject; wherein the condition or disease is a microbial infection, a viral infection, a fungal infection, or a cancer tumor, each characterized by a negatively charged surface on a membrane; wherein the method reduces an infusion related reaction, a severity of said infusion related reaction, or any combination thereof, relative to administering otherwise said same pharmaceutical composition over a time period of about 5 min to about 30 min; and wherein said pharmaceutical composition comprises:
(a) a peptide or pharmaceutically acceptable salt thereof having 100% sequence identity to:Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val- Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1); and
(b) at least one pharmaceutically acceptable: excipient, diluent, or carrier, and the pharmaceutical composition has a pH of about 4 to about 9 (see Copending App ‘414, claim 1).
Brown teaches bicarbonate as a potentiator for antimicrobial agents and claims a composition comprising an effective amount of (i) bicarbonate, at a concentration of about 20 mM to about 100mM, and (ii) an antimicrobial agent (see Brown, Front pg. and column 54, claim 1).
With respect to the claimed irrigation solution and the claimed synergistic effect of sodium bicarbonate with the peptide. MPEP 2112.01(II) states that "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. Id. In the instant case, the claimed irrigation solution comprises a pharmaceutically acceptable salt of a peptide with a sequence of SEQ ID NO: 1, which is also known in the prior art as WLBU2 as taught by Swedan, and sodium bicarbonate. Before the effective filing date of the claimed invention, both WLBU and sodium bicarbonate were known to individually elicit a synergistic effect in the presence of other antimicrobial agents. Thus, it must naturally follow that the claimed irrigation solution comprising aqueous sodium bicarbonate provides a synergistic effect with the claimed pharmaceutically acceptable salt of the peptide represented by SEQ ID NO: 1.
Since all the claimed elements were known in the prior art one skilled in the art would have combined the elements as claimed by known methods with no change in the respective functions (i.e., cationic antimicrobial peptide and antimicrobial agent potentiator/enhancer) and the combination would have yielded predictable results (i.e., irrigation solution). The instant claim would have been obvious because the combination of known elements would have yielded predictable results to one of ordinary skill in the art at the time of the invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending App ‘414 claims a method of treating condition by administering a composition comprising SEQ ID NO: 1. Additionally, SEQ ID NO: 1 in Copending App ‘414 is 100% identical to instant SEQ ID NO: 1. The instant invention would have been obvious to an ordinary skilled artisan because copending App ‘414 is drawn to a method of treating which encompasses a species of the instantly claimed irrigation solution. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
7. Claims 1, 3, 7, 11, 13, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 81 and 103-104, and 110-112 of copending Application No. 16/980,295 (reference application) PG Pub US20220249599A1, claim set filed 06/16/2026.
Regarding instant claims 1, 3, 7, 11, 13 and 22, Copending App ‘295 claims:
A method of treating a bacterial infection comprising a biofilm in a subject, wherein the biofilm is formed on a prosthetic joint implanted in the subject, comprising: performing proximal incising on the subject to expose the prosthetic joint, and irrigating the prosthetic joint in vivo with a pharmaceutical composition while the prosthetic joint is implanted, wherein the pharmaceutical composition comprises: a. a peptide or pharmaceutically acceptable salt thereof comprising a polypeptide of sequence: Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1), wherein the peptide or pharmaceutically acceptable salt thereof is present in the pharmaceutical composition at a concentration of about 1 mg/mL to about 10 mg/mL; and b. an excipient, wherein the excipient comprises a buffering agent (see Copending App ‘295, claim 81).
The method of claim 81, wherein the buffering agent comprises an agent selected from the group consisting of sodium bicarbonate, potassium bicarbonate, sodium carbonate, magnesium carbonate, magnesium lactate, magnesium glucomate, sodium citrate, sodium tartrate, sodium acetate, sodium polyphosphate, potassium polyphosphate, sodium pyrophosphate, potassium pyrophosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, potassium metaphosphate, calcium acetate, calcium glycerophosphate, and any combination thereof (see Copending App ‘295, claim 103).
The method of claim 103, wherein the buffering agent comprises sodium bicarbonate, potassium bicarbonate, sodium carbonate, or magnesium carbonate (see Copending App ‘295, claim 104).
The method of claim 81, wherein the peptide is present at a concentration of about 1 mg/mL (see Copending App ‘295, claim 110).
The method of claim 81, wherein the peptide is present at a concentration of about 3 mg/mL (see Copending App ‘295, claim 111).
The method of claim 81, wherein the peptide is present at a concentration of about 10 mg/mL (see Copending App ‘295, claim 112).
Although the claims at issue are not identical, they are not patentably distinct from each other because copending App ‘295 claims a method of treating a bacterial infection by administering a composition comprising SEQ ID NO: 1. Additionally, SEQ ID NO: 1 in Copending App ‘295 is 100% identical to instant SEQ ID NO: 1. With respect to the claimed irrigation solution and the claimed synergistic effect of sodium bicarbonate with the peptide. MPEP 2112.01(II) states that "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. Id. In the instant case, the claimed irrigation solution comprises a pharmaceutically acceptable salt of a peptide with a sequence of SEQ ID NO: 1, which is also known in the prior art as WLBU2, and sodium bicarbonate. Before the effective filing date of the claimed invention, both WLBU and sodium bicarbonate were known to individually elicit a synergistic effect in the presence of other antimicrobial agents. Thus, it must naturally follow that the claimed irrigation solution comprising aqueous sodium bicarbonate provides a synergistic effect with the claimed pharmaceutically acceptable salt of the peptide represented by SEQ ID NO: 1.
The instant invention would have been anticipated to an ordinary skilled artisan because copending App ‘295 is drawn to a method of treating which encompasses a species of the instantly claimed irrigation solution. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/CLAUDIA ESPINOSA/ Patent Examiner, Art Unit 1654
/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
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