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
Applicant's election with traverse of Group II in the reply filed on 10/29/24 was previously acknowledged. Election was made of ANP peptide or ANP peptide derivative and P. aeruginosa as the infection.
The requirement was deemed proper and made FINAL.
In the reply filed 4/28/25, Applicants amended claims 11 and 19-21.
In the reply filed 12/1/25, Applicants amended claims 11, 19-20 and 21. Claims 22-23 were newly added.
Claims 11-18 and 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 19-20 and 22-23 read on elected Group II and elected species and are under consideration.
Claim Rejections-Withdrawn
The rejection of claims 19-20 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn due to Applicants arguments.
The rejection of claims 19 and 20 under 35 U.S.C. 103 as being unpatentable over Lesouhaitier et al. (Journal of Innate Immunity 2019;11:227-241, published online 11/5/2018, cited on IDS) in view of Haywood et al. (Aust Presc 2011;34:112-114) is withdrawn due to amendment of the claims.
The rejection of claims 19-20 under 35 U.S.C. 102(a)(1) as being anticipated by Suffee et al. (“Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria” PNAS published online 1/16/2017) as evidenced by ThermoFisher Scientific (https://www.thermofisher.com/us/en/home/technical-resources/media-formulation.55.html accessed 8/4/25) is withdrawn due to amendment of the claims.
Claim Rejections - 35 USC § 112-Maintained
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.
The rejection of claims 19-20 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention is maintained and extended to claims 22 and 23.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Scope of the claimed genus
Claim 19 is drawn to a pharmaceutical composition comprising (a) a natriuretic peptide selected from the group consisting of (i) osteocrin, (ii) a lebetin, a lebetin fragment and (iii) an ANP peptide or ANP peptide derivative; and (b) an antibiotic effective against Pseudomonas aeruginosa or Staphylococcus aureus and (c) a pharmaceutically acceptable vehicle or excipient.
Claim 20 is drawn to a pharmaceutical antibacterial combination for therapeutically treating a bacterial infection associated with a Pseudomonas aeruginosa or Staphylococcus aureus bacterial biofilm in a subject in need thereof, the pharmaceutical antibacterial combination comprising: comprising (a) a natriuretic peptide selected from the group consisting of (i) osteocrin (ii) a lebetin, a lebetin fragment and (iii) an ANP peptide or ANP peptide derivative; and (b) an antibiotic effective against Pseudomonas aeruginosa or Staphylococcus aureus for simultaneous, separate, or sequential use with the natriuretic peptide and a pharmaceutically acceptable vehicle or excipient.
The USPTO provides claim terms with broadest reasonable interpretation in light of the specification. The instant specification defines ANP peptide and ANP derivative on p. 5-6. The term derivative according the specification includes one or more amino acid residues are chemically modified, truncated forms corresponding to the amino acids 4 or 5 to 28 of the whole length of ANP, ANP peptides in which 1 to 12 amino acids have been deleted or substituted or added while preserving the activity of WT ANP. The instant specification defines lebetin, lebetin fragment on p. 7-8. Lebetin fragment is defined as a fragment of at least 10 amino acids.
Assessment of whether species are support in the original specification
The instant specification discloses ANP (SEQ ID NO: 1), osteocrin (SEQ ID NO: 5) and lebetins 2alpha (SEQ ID NO: 8) and L1 beta (SEQ ID NO: 9) on biofilms of P. aeruginosa. The antibodies include tobramycin, ciprofloxacin, Colistin, Imipenem and Polymyxin B.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are -adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, the disclosure of ANP, osteocrin and lebetins 2alpha and L1 beta are not representative of derivatives and fragments. The instant specification does not specifically limit the derivatives or fragments to a specific sequence, therefore the genus of peptides that meets the limitations is enormous. The specification does not teach which amino acids are modified or which amino acids can be deleted, added or changed while still resulting in a natriuretic peptide that has the claimed ability to treat bacterial infections associated with biofilms. For example, the instant specification states that 1-12 amino acids of ANP can be deleted or substituted or added. If one considers that there are 20 natural amino acids and a great number of non-natural amino acids and the substitutions/deletions/additional can occur at any position of the peptide, the number of peptides that meet the requirement is quite large.
Therefore, disclosure of ANP (SEQ ID NO: 1), osteocrin (SEQ ID NO: 5) and lebetins 2alpha (SEQ ID NO: 8) and L1 beta (SEQ ID NO: 9) are not representative of the genus of claims 19-20.
Identifying characteristics and structure/function correlation
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe the structural, physical and/or chemical properties of derivatives and fragments of ANP, osteocrin and lebetin that leads to the claimed function of treating a bacterial infection associated with a P. aeruginosa or S. aureus biofilm. The data do not suggest the physical basis for the claimed activity and therefore do not describe which substitutions, deletions or additions could be made while preserving function.
This is an issue of written description. The specification does not make clear which proteins are in the genus and which are not because it does not describe the physical basis for the claimed activity. In other words, the specification does not describe which proteins to make.
In conclusion, for the reasons presented above, the skilled artisan would reasonably conclude that the inventors, at the time the application was filed had full possession of the ANP (SEQ ID NO: 1), osteocrin (SEQ ID NO: 5) lebetins 2alpha (SEQ ID NO: 8) and L1 beta (SEQ ID NO: 9) and antibiotics tobramycin, ciprofloxacin, Colistin, Imipenem and Polymyxin B.
Response to Arguments
Applicant's arguments filed 12/01/25 have been fully considered but they are not persuasive. Applicants argue that the claims were amended to limit the scope to P. aeruginosa and S. aureus infections, limit the natriuretic peptide and limit the antibiotic to those effective against P. aeruginosa and S. aureus. Applicants disclose the definitions of ANP derivative and lebetin fragment in the specification. Applicants argue that due to the disclosure, the applicants provide sufficient written description in accordance with 112(a). Applicants argue that this is confirmed by data in Ex. 5 in the specification and the data provided in Annex 5 of the Declaration.
These arguments were considered but are not persuasive. The Examiner will address the data and arguments separately in the Declaration in the “Response to Amendment” below. The Examiner agrees that the definitions of ANP derivative and lebetin fragments are provided in the specification. However, the definitions are extremely broad and include a great number of peptides. For example, ANP derivatives includes truncated forms wherein 1 to 12 amino acids are deleted, added or substituted. The ANP peptide derivatives are not limited by a particular length and can include up to 12 additions, substitutions and deletions. If one considers that there are 20 natural amino acids and a great number or non-naturally occurring amino acids, the number of peptides that meet the structural limitations is enormous. The lebetin fragments are not limited to 2a and 1beta. The definition includes lebetin fragments of at least 10 amino acids. Therefore, the data do not suggest the physical basis for the claimed activity and therefore do not describe which substitutions, deletions or additions could be made while preserving function. The specification only demonstrates activity for a small number of specific peptides but the claims encompass a large genus defined by functional activity rather than structure. Accordingly, the specification does not reasonable convey possession of the full scope of the claims invention and the written description requirement is not satisfied.
Claim 20 is 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 treatment biofilm of P. Aeruginosa with (a) ANP (SEQ ID NO: 1), osteocrin (SEQ ID NO: 5) and lebetins 2alpha (SEQ ID NO: 8) and L1 beta (SEQ ID NO: 9) and (b) tobramycin, ciprofloxacin, Colistin, Imipenem and Polymyxin B, does not reasonably provide enablement for treatment of bacterial infections associated with a S. aureus biofilm with osteocrin, a lebetin or lebetin fragment, an ANP peptide or ANP peptide derivative and an antibiotic effective against P. aeruginosa or S. aureus. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
As stated in MPEP 2164.01(a), “there are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
The factors to be considered when determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, were described in In re Wands, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) as:
1. the nature of the invention;
2. the breadth of the claims;
3. the state of the prior art;
4. the relative skill of those in the art;
5. the predictability or unpredictability of the art;
6. the amount of direction or guidance presented [by the inventor];
7. the presence or absence of working examples; and
8. the quantity of experimentation necessary [to make and/or use the invention.
(1) The Nature of the Invention and (2) The Breadth of the claims
Claim 20 is drawn to a pharmaceutical antibacterial combination for therapeutically treating a bacterial infection associated with a P. aeruginosa or S. aureus bacterial biofilm in a subject in need thereof, the pharmaceutical antibacterial combination comprising: comprising (a) a natriuretic peptide selected from the group consisting of (i) osteocrin (ii) a lebetin, a lebetin fragment and (iii) an ANP peptide or ANP peptide derivative; and (b) an antibiotic effective against P. aeruginosa or S. aureus for simultaneous, separate, or sequential use with the natriuretic peptide and (c) a pharmaceutically acceptable vehicle or excipient.
The instant specification defines ANP peptide and ANP peptide derivative on p. 5-6. The term derivative according the specification includes one or more amino acid residues are chemically modified, truncated forms corresponding to the amino acids 4 or 5 to 28 of the whole length of ANP, ANP peptides in which 1 to 12 amino acids have been deleted or substituted or added while preserving the activity of WT ANP. The instant specification defines lebetin, lebetin fragment on p. 7-8. Lebetin fragment is defined as a fragment of at least 10 amino acids.
The claims will be given its broadest reasonable interpretation. The applicable rule for interpreting the claims is that “each claim must be separately analyzed and given its broadest reasonable interpretation in light of and consistent with the written description.” See MPEP 2163(II)(1), citing In re Morris, 127 F.3d 1048, 1053-1054; 44 USPQ2d 1023, 1027 (Fed. Cir. 1997). In view of this rule, Claim 20 is drawn to treatment of any bacterial infection associated with a P. aeruginosa or S. aureus biofilm with (i) osteocrin (ii) a lebetin, a lebetin fragment (iii) an ANP peptide or ANP peptide derivative; and (b) an antibiotic effective against P. aeruginosa or S. aureus.
(3) The state of the prior art and (5) The predictability or unpredictability of the art
The instant application is enabling for treatment biofilm of P. Aeruginosa with (a) ANP (SEQ ID NO: 1), osteocrin (SEQ ID NO: 5) and lebetins 2alpha (SEQ ID NO: 8) and L1 beta (SEQ ID NO: 9) and (b) tobramycin, ciprofloxacin, Colistin, Imipenem and Polymyxin B.
However, the prior art teaches that biofilms have the ability to survive in the presence of high concentrations of antibiotics (Lebeaux et al. Microbiol Mol Biol Rev. 2014 Sep;78(3):510-543) (Abstract). Lebeaux et al. teach that due to their high tolerance toward antibiotics, these chronic tissue-related and device-related infections are difficult to treat and expose the patient to the risk of recurrence (p. 511, top of 2nd col.). Labeaux et al. teach that once a biofilm is established, bacteria are able to survive after various types of physicochemical aggression, including UV light, heavy metals, acidity, changes in hydration or salinity, and phagocytosis (15–19). In addition, biofilm bacteria also display a characteristic ability to withstand antibiotic-mediated killing, which is directly responsible for a significant number of therapeutic difficulties encountered in clinical settings (p. 511,2nd col. 3rd para.).
Mirghani et al. (AIMS Microbiology, 8(3):239-277 (2022)) teach biofilms are aggregates of bacteria, in most cases, which are resistant usually to broad-spectrum antibiotics in their typical concentrations or even in higher doses. A trend of increasing multi-drug resistance in biofilms, which are responsible for emerging life-threatening nosocomial infections, is becoming a serious problem (Abstract). Mirghani et al. teach the spread of multi-drug resistant microorganisms found in biofilms is worsening situations all around the globe and emerging as a new threat to public health (Conclusion).
Therefore, the state of the art at the time of the application is that the treatment of biofilms is challenging and complex. Adding to the complexity are the many different microorganisms associated with biofilms. It is noted that pharmaceutical and biological art is generally unpredictable, requiring each embodiment to be individually assessed for physiological activity. Given this fact, historically the development of new drugs has been difficult and time-consuming. Adding to the unpredictability is the trend of increasing multi-drug resistance in biofilms (Mirghani et al.). There is no absolute predictability, even in view of the high level of skill in the art.
(4) The relative skill of those in the art
MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
(6) The amount of direction or guidance presented (by the inventor) and (7) The presence or absence of working examples
The applicant provided sufficient guidance or direction regarding the potential treatment of P. aeruginosa biofilms with (a) ANP (SEQ ID NO: 1), osteocrin (SEQ ID NO: 5) and lebetins 2alpha (SEQ ID NO: 8) and L1 beta (SEQ ID NO: 9) and (b) tobramycin, ciprofloxacin, Colistin, Imipenem and Polymyxin B (see Examples 1-11).
In contrast, the applicant provides little in way of direction or guidance regarding treating bacterial infections associated with S. aureus biofilms. It should be noted that P. aeruginosa is gram negative bacteria and S. aureus is gram positive. Therefore, the biofilms are structurally and chemically different. The specification only demonstrates successful treatment of P. aeruginosa biofilms and does not provide data that the same treatment would be effective against S. aureus biofilms. As indicated above, the bacteria are distinct (gram positive vs gram negative) resulting in biofilms that differ structurally and chemically and one of ordinary skill in the art would not reasonably expect the treatment effective for biofilms against one to be effective against the other without undue experimentation.
(8) The quantity of experimentation necessary (to make and/or use the invention)
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
In conclusion, the instant application is enabled for the treatment of P. aeruginosa biofilms with (a) ANP (SEQ ID NO: 1), osteocrin (SEQ ID NO: 5) and lebetins 2alpha (SEQ ID NO: 8) and L1 beta (SEQ ID NO: 9) with (b) tobramycin, ciprofloxacin, Colistin, Imipenem and Polymyxin B.
Response to Arguments
Applicant's arguments filed 12/01/25 have been fully considered but they are not persuasive. Applicants argue that the claims were amended to limit the scope to P. aeruginosa and S. aureus infections, limit the natriuretic peptide and limit the antibiotic to those effective against P. aeruginosa and S. aureus. Applicants argue that the claim is not drawn to treating all bacterial infections associated with a biofilm just those of P. aeruginosa and S. aureus. Applicants argue that the effectiveness would have been apparent to a skilled artisan in view of the instant application. Applicants argue that the Office already recognized enablement of claim 20 with respect to P. aeruginosa using ANP, osteocrin, lebetin 2a and 1beta with tobramycin, ciprofloxacin, colistin, imipenem and polymyxin B. Applicants argue that a skilled artisan would have found claim 20 enabled for S. aureus based on the data in the originally filed application. Applicants argue that the data in Annex 2 shows ANP and lebetin were able to disperse S. aureus strains.
These arguments were considered but are not persuasive. The Examiner will address the data and arguments separately in the Declaration in the “Response to Amendment” below. The instant specification only demonstrates activity for a limited number or peptides, but the claims encompass a large genus of ANP peptide derivatives and lebetin fragments that are not limited by a specific length or sequence. Therefore, a person of ordinary skill in the art would need to practice undue experimentation to determine which peptides had the claimed function. While the specification demonstrates activity for certain peptides against P. Aeruginosa biofilms, the claims are not limited to those peptides or bacterial species. In addition, P. aeruginosa and S. aureus biofilms are different bacterial species (gram negative vs. gram positive) so success with one would not enable treatment with the other. Due to the breadth of the claims, the unpredictability of peptide activity and structure and the difference between bacterial biofilms, one of ordinary skill in the art would need to engage in undue experimentation to practice the full scope of the claims. Therefore, the enablement rejection is maintained.
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.
Claims 19-20 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Lesouhaitier et al. (Journal of Innate Immunity 2019;11:227-241, published online 11/5/2018, cited on IDS) and Chang et al. (The AAPS Journal (April 2019) 21, 49) in view of Haywood et al. (Aust Presc 2011;34:112-114) and. This is a NEW rejection necessitated by amendment of the claims.
The applied reference has common inventors (Lesouhaitier, Clamens, Louis, Rodrigues, and Feuilloley) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Lesouhaitier et al. teach that biofilms are complex microbial communities of cells that are attached to a substream, an interface or to each other and embedded into a matrix of self-produced extracellular polymeric compounds (p. 227, bottom of 2nd col.). Lesouhaitier et al. teach a search for new strategies or bacterial targets to counteract bacterial infection and/or biofilm formation, the potential as antimicrobials of eukaryotic communication factors released constantly by hosts cells during infections (natriuretic peptides) has emerged (p. 228, 1st col, last para). Lesouhaitier et al. teach that natriuretic peptide were shown to modify the virulence of P. aeruginosa and P. fluorescens (p. 228, 2nd col, last para.). Lesouhaitier et al. teach that biofilm formation activity of S. aureus was inhibited by ANP (p. 238, 1st col.). Lesouhaitier et al. teach the data suggests that CNP or CNP derivatives could be interesting drugs for inhibition of P. aeruginosa biofilm formation either alone or in combination with antibiotics. Lesouhaitier et al. teach that CNP derivatives such as osteocrin could be an interesting candidate (p. 235, 1st col.).
Lesouhaitier et al. does not teach an example of a combination of a natriuretic peptide, such as ANP or ostreocrin (CNP derivative) and an antibiotic effect against P. aeruginosa, however the teachings of Chang et al. cure this deficiency.
Chang et al. teach that CF patients suffer from multi-species bacterial colonization in the lung including P. aeruginosa (p. 1, 1st para.). Chang et al. teach combination treatment of biofilms of P. aeruginosa with phages and antibiotics (p. 2, 1st. para.). Chang et al. teach a combination of a phage and Ciprofloxacin (p. 2, 1st col.). As evidenced by claim 23, ciprofloxacin is an antibiotic against P. aeruginosa. Chang et al. teach synergistic effect of the phage and ciprofloxacin against P. aeruginosa biofilms (Fig. 1-4).
With respect to claims 19-20 and 22-23, It would have been obvious to a person of ordinary skill in the art to combine a natriuretic peptide such as ANP or osteocrin with an antibiotic effective against P. aeruginosa in order to make a pharmaceutical composition for inhibition or treatment of P. aeruginosa biofilms. A person of ordinary skill in the would have a motivation to combine them because Lesouhaitier et al. teach that the combination would be an interesting drug composition for inhibition of P. aeruginosa biofilms and Chang et al. teach combination of agents including the antibiotic ciprofloxacin was effective in inhibiting growth of P. aeruginosa biofilms. There is a reasonable expectation of success given that Lesouhaitier et al. suggest the combination for inhibition of P. aeruginosa films and Chang et al. teach that a combination of a phage and ciprofloxacin was synergistically effective in inhibiting growth of P. aeruginosa biofilm.
With respect to claim 20 and the limitation “for therapeutically treating a bacterial infection…” and “for simultaneous, separate, or sequential use with the natriuretic peptide” is regarded as “intended use”. Please note that the "intended use" of a composition or product will not further limit claims drawn to a composition or product. See, e.g., Ex parte Masham, 2 USPQ2d 1647 (1987) and In Re Hack 114, USPQ 161. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim limitation. In the instant case, the prior art meets the limitations of the claims and is capable of the intended use.
Lesouhaitier et al. do not teach a pharmaceutically acceptable excipient. However, the teachings of Haywood et al. cure this deficiency.
With respect to claim the limitation “(c) a pharmaceutically acceptable vehicle or excipient” (claims 19 and 20), Haywood et al. teach pharmaceutical excipients are substances that are included in a pharmaceutical dosage form not for their direct therapeutic action, but to aid the manufacturing process, to protect, support or enhance stability, or for bioavailability or patient acceptability. They may also assist in product identification and enhance the overall safety or function of the product during storage or use (bottom of p. 112, 1st col.). Table 1 discloses common excipients. Haywood et al. teach medicines contain ingredients other than the active drug that are essential for their manufacture, stability and function (Conclusion).
It would be obvious to a person of ordinary skill in the art to include a pharmaceutically acceptable excipient in the composition of Lesouhaitier et al. and Change et al. in order to aid the manufacturing process, to protect, support or enhance stability, or for bioavailability or patient acceptability. There is a reasonable expectation of success given that pharmaceutically acceptable excipients are well known and routine in the art.
With respect to the limitation (Claim 20) “wherein the pharmaceutical antibacterial combination is a fixed combination in a single unit dosage form or a kit for combined administration in which the natriuretic peptide and the antibiotic can be administered independently at the same time or separately at time intervals”, it would have been obvious for the combination to be in a fixed combination in a single unit dosage so the components can easily be administered together. There is a reasonable expectation because Lesouhaitier et al. and Chang et al. makes obvious the combination of natriuretic peptide and antibiotic.
Response to Arguments
Applicant's arguments filed 12/01/25 have been fully considered but they are not persuasive. Applicants argue that the claims were amended to limit the scope to P. aeruginosa and S. aureus infections, limit the natriuretic peptide and limit the antibiotic to those effective against P. aeruginosa and S. aureus. Applicants argue that Lesouhaitier et al. relates to biofilm formation inhibition (i.e. prevents biofilm formation), which is different that than dispersion of already formed biofilm. Applicants argue that numerous publication have established inhibition of biofilm formation is completely different than dispersion. Applicants argue that a skilled artisan would not have a reasonable expectation of success that teachings regarding a composition effective at inhibiting biofilm formation would be effective for dispersing an existing biofilm because the mechanisms are different. Applicants refer to the previous submitted Declaration (April 22, 2025). Applicants argue that a peptide able to prevent the formation of biofilms is not necessarily able to disperse it. Applicants argue that Lesoushaitier may suggest the use of BNP or CNP to prevent formation of P. aeruginosa biofilms, however the reference does not suggest they are able to disperse it.
These arguments were considered but are not persuasive as the claims are product claims, not method of use claims. The claims do not require administration or treatment of the biofilms. The recitation of treating biofilms represents an intended use and does not structurally distinguish the claimed composition from the composition of the prior art. The prior art composition is the same regardless of whether it is used to prevent formation of a biofilm or treating a bacterial infection associated with a biofilm. Importantly, Lesouhaitier et al. suggest administering ANP or osteocrin with an antibiotic in order to make a pharmaceutical composition for inhibition or treatment of P. aeruginosa biofilms. Importantly, the combination would inherently have all of the activities and properties of the composition of claim 20. The MPEP § 2112 states: “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference ‘[t]he PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same…[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzqerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433- 34 (CCPA 1977)).” In other words, Lesouhaitier et al. teach, ANP or osteocrin with an antibiotic in order to make a pharmaceutical composition for inhibition of P. aeruginosa biofilms and Chang et al. makes obvious including an antibiotic for P. aeruginosa infection, therefore the same composition would necessarily treat the biofilms. Moreover, MPEP 2112.01 states: “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.
Response to Amendment
The Declaration under 37 CFR 1.132 filed 12/1/25 is insufficient to overcome the rejection of the claims as set forth in the last Office action. The Declaration discloses a peptide derivative of ANP (peptide 1) was able to disperse a P. aeruginosa biofilm. Peptide 1 differs from ANP by a single amino acid. The Declaration states that ANP and peptide 1 were able to effectively disperse the biofilm.
The Examiner considered the results of Annex 1 and the results show a single ANP peptide derivative was able to disperse the biofilm. However, the results are not commensurate in scope with the claims. MPEP 2145 states: When considering whether proffered evidence is commensurate in scope with the claimed invention, Office personnel should not require the applicant to show unexpected results over the entire range of properties possessed by a chemical compound or composition. See, e.g., In re Chupp, 816 F.2d 643, 646, 2 USPQ2d 1437, 1439 (Fed. Cir. 1987). Evidence that the compound or composition possesses superior and unexpected properties in one of a spectrum of common properties can be sufficient to rebut a prima facie case of obviousness. Id. For example, a showing of unexpected results for a single member of a claimed subgenus, or a narrow portion of a claimed range would be sufficient to rebut a prima facie case of obviousness if a skilled artisan “could ascertain a trend in the exemplified data that would allow him to reasonably extend the probative value thereof.” In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Evidence of the nonobviousness of a broad range can be proven by a narrower range when one skilled in the art could ascertain a trend that would allow him to reasonably extend the probative value thereof.). But see, Grasselli, 713 F.2d at 743, 218 USPQ at 778 (evidence of superior properties for sodium containing composition insufficient to establish the non-obviousness of broad claims for a catalyst with “an alkali metal” where it was well known in the catalyst art that different alkali metals were not interchangeable and applicant had shown unexpected results only for sodium containing materials). In the instant case, the claims are not commensurate in scope with the claims because a ANP peptide can have 1 to 12 amino acid substitutions, deletions or additions. The example of peptide 1 with a single amino acid substitution is insufficient to overcome the prima facie case of obviousness because the skilled artisan could not ascertain a trend in the exemplified data that would allow him to reasonably extend the probative value thereof.
Applicants provide Annex 2 disclosing dispersion of preformed biofilm of S. aureus with ANP and lebetin 1beta. Applicants state that the results show that both ANP and lebetin 1b were able to efficiently disperse mature S. aureus biofilm.
This was not persuasive as the asserted dispersion of S. aureus biofilm is supported only by qualitative images. The Declaration does not provide quantitative measurements of biofilm reduction or dispersal as in Annex 1 and the instant specification. Annex 2 also does not provide the sample size and statistical analysis demonstrating that the differences were statistically significant (Please see MPEP 716.02). For the reasons presented above, the Declaration was insufficient to overcome the rejections of record.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/TARA L MARTINEZ/Examiner, Art Unit 1654