FINAL 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 .
Status of the Claims
This action is in response to papers filed 06/19/2025 in which claims 13-21 and 25-28 were withdrawn; and claims 1-12 and 22-24 were amended. All the amendments have been thoroughly reviewed and entered.
Claims 1-12 and 22-24 are under examination.
Withdrawn Rejection
The Examiner has re-weighted all the evidence of record. Any rejection and/or objection not specifically addressed below is hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Maintained-Modified Rejections
Modification Necessitated by Applicant’s Claim Amendments
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.
Claim(s) 1-5, 7-11 and 22-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Loontjens et al (US 2018/0298202 A1) in view of Chiattello et al (WO 2018/022926 A1), and as evidenced by Li et al (The Journal of Physical Chemistry, 2017, 121: 6416-6424; cited IDS filed 1/09/2021).
Regarding claim 1, Loontjens teaches a method of providing a substrate with an antimicrobial coating on the surface of the substrate, the antimicrobial coating comprises polycondensation of AB2 monomers comprising a secondary amine as A-group and blocked isocyanates as B-groups to obtain a low number average molecular weight polyurea of at least 2500 Da, contacting said polyurea with a surface grafted with coupling agent to covalently anchor the polyurea, and continuing polycondensation to obtain a hyperbranched polyurea coating; alkylating a polyethyleneimine (PEI) to produce a hydrophobic N-alkylating PEI having antimicrobial properties; and immobilizing onto said coating the hydrophobic N-alkylating polyethyleneimine (PEI) (Abstract; [0001]-[0032], [0036]-[0048], [0057]-[0066]; claims 1-19). Loontjens teaches the polyethyleneimine (PEI) (not alkylated) is first tethered to the coating ([0033] and [0061]; claim 6).
While Loontjens teaches the PEI is an alkylated PEI (a quaternized polyamine), it would have been obvious substitute the alkylated PEI for a non-alkylated PEI, and produce the resultant antimicrobial coating. One of ordinary skill in the art would have been motivated to modify the method of providing a substrate with antimicrobial coating of Loontjens and use a non-alkylated PEI because Chiattello provided the guidance to do so by teaching that a polymer-based antimicrobial composition for use as an antimicrobial coating on a substrate can use a non-alkylated PEI as the polyamine-functionalized polymer and is not required to use an alkylated PEI to produce the desired antimicrobial properties of the coating (Chiattello: Abstract; [0013]-[0036]). Chiattello further indicated that chemical modification of PEI such as chemically or structurally modifying PEI to include alkyl and/or quaternary ammonium groups, is not required to achieve antimicrobial properties, as non-modified PEI has the ability to kill both gram positive and gram negative bacteria (Chiattello: [0028]). Chiattello further indicated that it is preferred that a chemically modified PEI is not used as chemical modification requires expensive, low yield, organic chemical processes that use toxic chemicals that are harmful to humans and the environment (Chiattello: [0028]). In addition, Loontjens indicated that immobilization or tethering (covalent bonding) of the PEI can be via PEI that has not been alkylated (Loontjens: [0033] and [0061]; claim 6). Thus, an ordinary artisan knowing the drawbacks of using alkylated PEI would have looked to modifying the method of providing a substrate with antimicrobial coating of Loontjens and use a non-alkylated PEI (instead of an alkylated PEI) with a reasonable expectation of obtaining a resultant antimicrobial coating desired by Loontjens, as Chiattello suggested that non-alkylated PEI has the ability to kill both gram positive and gram negative bacteria, and that an alkylated PEI is not required to achieve an antimicrobial coating, and achieve Applicant’s claimed method with reasonable expectation of success.
While Loontjens does not teach the use of an aqueous salt solution in the method of producing the antimicrobial coating, it would have been obvious to include an aqueous salt solution containing an inorganic salt such as sodium bromide, sodium iodide, potassium bromide, potassium chloride, potassium iodide, potassium phosphate, magnesium sulfate, calcium nitrate, or calcium sulfate in the method of providing the antimicrobial coating onto the surface of the substrate of Loontjens, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Chiattello provided the guidance to do so by teaching that the antimicrobial coating (PEI polymer) can further be contacted a salt solution, which can affect the ability of the cationic polymer (PEI) to absorb to the surface of a substrate and create film by improving adsorption or adhesion of the PEI onto the surface of the substrate (Chiattello: [0082]-[0083]). Chiattello indicated that the cationic polymer (PEI) will act as any other non-polar polymer would in a high ionic strength solution and being to minimize interactions with the solvent, which can lead to a much more clumped and density polymer deposited onto the surface and improve adsorption or adhesion (Chiattello: [0082]). Thus, ordinary artisan seeking to provide a desired antimicrobial coating with improved adsorption or adhesion of the PEI onto the surface of the substrate would have looked to including an aqueous salt solution containing an inorganic salt such as sodium bromide, sodium iodide, potassium bromide, potassium chloride, potassium iodide, potassium phosphate, magnesium sulfate, calcium nitrate, or calcium sulfate in the method of providing the antimicrobial coating onto the surface of the substrate of Loontjens, such that the PEI polymer is in contact with the salt solution, thereby increasing the density the PEI polymer deposited onto the surface, and achieve Applicant’s claimed invention with reasonable expectation of success.
It would also have been reasonably obvious that the inclusion of an aqueous salt solution containing an inorganic salt such as sodium bromide, sodium iodide, potassium bromide, potassium chloride, potassium iodide, potassium phosphate, magnesium sulfate, calcium nitrate, or calcium sulfate in the method of providing the antimicrobial coating onto the surface of the substrate of Loontjens per guidance from Chiattello would implicitly result in “enhancing a charge density” of the antimicrobial PEI coating because as discussed above, Chiattello indicated that the cationic polymer (PEI) will act as any other non-polar polymer would in a high ionic strength solution and being to minimize interactions with the solvent, which can lead to a much more clumped and density polymer deposited onto the surface and improve adsorption or adhesion (Chiattello: [0082]).
As evidence by Li, an inorganic salt such as sodium bromide, sodium iodide, potassium bromide, potassium chloride, potassium iodide, potassium phosphate, magnesium sulfate, calcium nitrate, or calcium sulfate, has a polarizability α37 of at least 4 (Li: page 6418, Table 1).
Regarding claims 2-4, as discussed above, Chiattello provided the guidance include an aqueous salt solution containing an inorganic salt such as sodium bromide, sodium iodide, potassium bromide, potassium chloride, potassium iodide, potassium phosphate, magnesium sulfate, calcium nitrate, or calcium sulfate in the method of providing the antimicrobial coating onto the surface of the substrate of Loontjens. As evidenced by Li, an inorganic salt such as sodium bromide, sodium iodide, potassium bromide, potassium chloride, potassium iodide, potassium phosphate, magnesium sulfate, calcium nitrate, or calcium sulfate, has a polarizability α37 of at least 4 (Li: page 6418, Table 1). Particularly, Li discloses an inorganic salt such as sodium bromide has a polarizability α37 of about 4.8 , sodium iodide has a polarizability α37 of about 7.4, potassium bromide has a polarizability α37 of about 5.5, and potassium iodide has a polarizability α37 of about 8 (Li: page 6418, Table 1).
Regarding claim 5, as discussed above, Chiattello provided the guidance for using a non-alkylated PEI as the PEI of Loontjens.
Regarding claims 7 and 22, Loontjens teaches the substrate is a medical grade material selected from medical grade polydimethylsiloxane elastomer (PDMS), polyurethane, and polyvinylchloride (PVC) ([0012], [0017], [0036], and [0047]).
Regarding claims 8 and 23, Loontjens teaches the substrate is a metal which is biocompatible with the mammalian body, preferably selected from the group consisting of titanium, titanium-alloy, tantalum and tantalum-alloy ([0012], [0017], [0037], and [0046]).
Regarding claim 9, as discussed above, Loontjens teaches contacting said polyurea with a surface grafted with coupling agent to covalently anchor the polyurea to the substrate.
Regarding claims 10-11 and 24, as discussed above, Loontjens teaches the coating is a hyperbranched polyurea coating.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the reference, especially in the absence of evidence to the contrary.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Loontjens et al (US 2018/0298202 A1) in view of Chiattello et al (WO 2018/022926 A1), and as evidenced by Li et al (The Journal of Physical Chemistry, 2017, 121: 6416-6424; cited IDS filed 1/09/2021), as applied to claim 1 above, and further in view of Hernandez-Montelongo et al (Colloids and Surface B: Biointerfaces, 2018, 164: 370-378; cited IDS filed 1/09/2021).
The method of claim 1 is discussed above, said discussion being incorporated herein in its entirety.
However, Loontjens and Chiattello do not teach contacting the polyamine-functionalized polymer with one or more proteinaceous substances of claim 6.
Regarding claim 6, Montelongo teaches electrostatic immobilization of antimicrobial peptide on polyethyleneimine to provide a higher antibacterial effect (Abstract; pages 377-378).
It would have been obvious to one of ordinary skill in the art to modify the method of Loontjens in view of Chiattello to further comprise immobilizing an antimicrobial peptide on the surface of the PEI, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Montelongo provided the guidance to do by teaching that an antimicrobial peptide can be electrostatically immobilized onto PEI so as to provide a resultant PEI product with enhanced antibacterial effect (Montelongo: Abstract; pages 377-378). Thus, an ordinary artisan seeking to maximize the antimicrobial effect of the coating of Loontjens in view of Chiattello would have looked to electrostatically immobilized onto PEI an antimicrobial peptide, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the reference, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 06/19/2025 have been fully considered but they are not persuasive.
Applicant argues:
“Chiattello concerns an antimicrobial composition that is applied as a "removable self-sanitizing film" to a surface to be coated. Thus, Chiattello is not concerned with covalently coating a substrate with a polyamine-functionalized polymer. Instead, Chiattello merely deposits non-covalently a PEI polymer onto a substrate to form a removable film. This is merely a precipitation process, which is unrelated to the presently claimed permanent, covalent attachment to an outer surface of a substrate.” (Remarks, page 10, 2nd paragraph).
In response, the Examiner disagrees. The 103 rejection is based on the combined teachings of Loontjens and Chiattello, in which the primary reference of Loontjens has already taught the covalently coated of a polyamine-functionalized polymer (PEI-functionalized polyurea antimicrobial coating) onto a surface of a substrate (see 103 rejection, pages 3-4 of this office action).
Applicant argues that Chiattello’s use of salt in paragraph [0082] “is similarly related to use of a precipitation process, and would not have motivated the skilled person to introduce salt into the Loontjens polymerization method..” Thus, Applicant alleges that “Chiattello uses salt for promoting clumping and non-covalent adhesion of a polymer to a surface, which is not relevant to the polymerization reaction in Loontjens, or in the present invention, which does not involve salt during polymerization or coating.” (Remarks, page 10, 2nd paragraph).
In response, the Examiner disagrees. The 103 rejection is not drawn to including salt solution of Chiattello into the polymerization reaction of Loontjens, but rather including an aqueous salt solution containing an inorganic salt such as sodium bromide, sodium iodide, potassium bromide, potassium chloride, potassium iodide, potassium phosphate, magnesium sulfate, calcium nitrate, or calcium sulfate in the method of providing the antimicrobial coating onto the surface of the substrate of Loontjens. See 103 rejection, pages 3-7 of this office action. Thus, Loontjens and Chiattello are properly combined to render obvious Applicant’s claimed method.
Applicant argues “compared to the present invention, the salt in Chiattello's coating composition acts at a different stage of the process, namely during the formation and adhesion of the polymer.” Applicant alleges “salt is required to be present during a later step, after the polymer has been covalently applied to a substrate.” Thus, Applicant alleges “Chiattello provides no teaching or suggestion of using salt after the film has already been applied to a surface; rather, in Chiattello salt is used to promote the coating process itself.” (Remarks, page 10, last paragraph to page 11).
In response, the Examiner disagrees. Paragraph [0082] of Chiattello teaches the already formed polymer is contacted with the salt solution to form the antimicrobial composition in which the salt solution improved adsorption or adhesion of the polymer onto the surface by increasing the density of polymer deposited onto the surface. Thus, Chiattello does provide guidance for and render obvious contacting of PEI polymer with a salt solution to enhance charge density of the PEI polymer on the surface of the substrate.
Applicant argues “the salt serves the function of increasing the charge density of the coating and therefore the antibacterial effect, which is not at all found either in Loontjens or in Chiattello. The particular use of the salt solution in step (b) of claim 1 has been emphasized in the presently amended claim, which now states that the salt solution is contacted with the coated substrate. Claim 1 also has been amended to point out the effect of the salt treatment to increase in charge density. The combined teachings of the cited references do not teach or suggest either this use of salt or the significant increase in charge density.” Thus, Applicant alleges that “Loontjens, Chiattello, and Li fail to disclose or suggest the addition of salt to an already formed coating to enhance the antimicrobial effect.” (Remarks, top of page 11).
In response, the Examiner disagrees. As discussed above in the pending 103 rejection, it would also have been reasonably obvious that the inclusion of an aqueous salt solution containing an inorganic salt such as sodium bromide, sodium iodide, potassium bromide, potassium chloride, potassium iodide, potassium phosphate, magnesium sulfate, calcium nitrate, or calcium sulfate in the method of providing the antimicrobial coating onto the surface of the substrate of Loontjens per guidance from Chiattello would implicitly result in “enhancing a charge density” of the antimicrobial PEI coating because as discussed above, Chiattello indicated that the cationic polymer (PEI) will act as any other non-polar polymer would in a high ionic strength solution and being to minimize interactions with the solvent, which can lead to a much more clumped and density polymer deposited onto the surface and improve adsorption or adhesion (Chiattello: [0082]).
Applicant is noted that the Specification disclosed that “the invention provides a strongly adhered antimicrobial coating …” (Specification, pages 22-23), which appeared the be same objective obtained in Chiattello when contacting or reacting of the cationic polymer (PEI polymer) with salt solution, as Chiattello established supra that cationic polymer (PEI) will act as any other non-polar polymer would in a high ionic strength solution (salt solution) and being to minimize interactions with the solvent, which can lead to a much more clumped and density polymer deposited onto the surface and improve adsorption or adhesion.
Accordingly, Loontjens and Chiattello are properly combined in the pending 103 rejection to render obvious Applicant’s claimed method.
For at least the reasons discussed above, claims 1-11 and 22-24 remain rejected as being obvious and unpatentable over the combined teachings of the cited prior arts in the pending 103 rejections as set forth in this office action.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: as previously discussed, the coupling agent of claim 12 is not taught or suggested in the prior art. Thus, if claim 1 is amended to include the coupling agent of claim 12, claim 1 would be allowable. Accordingly, claim 12 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-11 and 22-24 are rejected.
Claim 12 is objected.
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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/DOAN T PHAN/ Primary Examiner, Art Unit 1613