DETAILED ACTION
Receipt is acknowledged of applicant’s Amendment/Remarks filed 10/14/2025.
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
Claims 1, 7 and 49 have been amended. Claims 2, 3, 5, 8, 10-13, 15-17, 19, 21-42, 44 and 50 have been cancelled. No claims are newly added. Accordingly, claims 1, 4, 6, 7, 9, 14, 18, 20, 43, 45-49 and 51-58 remain pending in the application. Claims 18, 43, 45, 47, 54 and 55 stand withdrawn from further consideration, without traverse. Accordingly, claims 1, 4, 6, 7, 9, 14, 20, 46, 48, 49, 51-53 and 56-58 are currently under examination.
Information Disclosure Statement
The IDS filed 7/9/2025 has been considered. A signed copy is enclosed herewith.
Maintained Rejections
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 49, 51-53, 56 and 58 stand rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clevenger et al. (US 2010/0215643 A1, Aug. 26, 2010, hereafter as “Clevenger”) as evidenced by Smolecule (see PTO-892).
The claimed invention is drawn to a construct comprising: a) polymer surface comprising a polymer selected from the group consisting of polyalkanes, polyalkylarenes, polyolefins, polythiols and polyphosphines, said surface chemically accessible hydroxyl groups introduced by chemical oxidation and reactive with inorganic alkoxides; b) an inorganic oxide adhesion layer chemically bonded to the hydroxyl groups of said polymer surface, said inorganic oxide adhesion layer comprising surface oxide groups; c) a self-assembled phosphonate monolayer (SAMP) bonded to the surface of said inorganic oxide adhesion layer; and d) an anti-infective agent covalently bound to the SAMP.
Regarding instant claim 49, Clevenger teaches functionalization of substrates that allow for binding of anti-infective agents to said functionalized surfaces such that said surfaces have been modified to have anti-infective properties (abstract, [0002], [0053]-[0055] and [0063]-[0064]; Fig. 1; Examples). Clevenger teaches an activated surface comprising chemically accessible, reactive functional groups and an inorganic alkoxide adhesion layer chemically bonded to said reactive functional groups ([0031]-[0033]; Examples). Clevenger teaches the particular surface reactive functional groups, hydroxyl (-OH) and amino (-NH) groups ([0031]). Clevenger teaches that the surfaces (substrate) can be a polymer, e.g., polysiloxanes, polyethylene (a polyolefin) and polypropylene (a polyolefin) ([0013]-[0015] and [0017]; claim 30). Clevenger teaches the inclusion of a self-assembled monolayer composed of phosphonates wherein said layer is covalently bonded to functional groups ([0040], [0046] and [0048]). Clevenger also teaches a self-assembled phosphate monolayer bonded to a native oxide surface, wherein the self-assembled phosphonate monolayer is operable to bond an anti-infective agent (claim 67). Clevenger further teaches covalent bonding of the phosphonate film to the anti-infective agents ([0016]-[0017] and [0040]).
It is noted that that the instant claim and its depending claims are deemed product-by-process claims due to the limitation, “introduced by chemical oxidation” and as such, determination of patentability is based on the product itself, not by the method in which it is made. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process (MPEP 2113). As explained above, Clevenger teaches the particular surface reactive functional groups, hydroxyl (-OH) and amino (-NH) groups ([0031). While Clevenger does not expressly teach how the functional groups are introduced, said functional groups are nonetheless present. The product of Clevenger appears to be structurally the same as that of the claimed product. Thus, the teachings of Clevenger meet the limitations of the claim.
Regarding instant claim 51, Clevenger teaches alkoxides of the particular metals, Ti, Zr, Al, Nb, Ta, Sn and V ([0055]).
Regarding instant claims 52 and 53, Clevenger teaches the particular phosphonate, 11-hydroxyundecylphosphonic acid ([0104]) which has the claimed phosphonic acid structure wherein R is a substituted alkyl and the substitution consists of a hydroxyl functional group. While Clevenger does not explicitly state that said phosphonate possesses a cell-adhesive property, 11-hydroxyundecylphosphonic acid is known to be cell-adhesive as evidenced by Smolecule (page 3, Biological Activity paragraph).
Regarding instant claim 56, Clevenger teaches the particular anti-infective agents, chlorhexidine, quaternary ammonium cations (e.g., benzalkonium chloride), quaternary ammonium dendrimers, and cationic species ([0035] and [0038]).
Regarding instant claim 58, Clevenger, as discussed above, teaches surface oxides ([0014]-[0016]; claim 67), wherein the surface oxide comprises alkoxide groups ([0014]-[0015], [0033] and [0046]).
Thus, the teachings of Clevenger render the instant claims anticipated.
Response to Arguments
Applicant's arguments, filed 10/14/2025, regarding the 102 rejection over Clevenger have been fully considered but they are not persuasive.
Applicant argues that the polymers recited lack surface hydroxyl groups, which must be added by the oxidation processes disclosed in the present application. Applicant asserts that Clevenger lists these polymers as suitable substrates but does not describe or enable any oxidation or amination step to generate reactive functional groups on these surfaces. Remarks, page 8.
In response, it is respectfully submitted that the examiner agrees that Clevenger teaches the claimed polymers as suitable substrates (e.g., polyolefins). Clevenger also teaches that the surface may virtually be any material to include metals, polymers, ceramics, etc. which is amenable to receiving a functionalizing layer having acidic protons, such as -OH or -NH groups ([0031]). While Clevenger does not explicitly describe oxidation or amination step to generate reactive functional groups, the teachings of Clevenger imply that in order to use suitable substrates such as those without -OH or -NH groups (e.g., polypropylene), a step to generate said reactive functional groups is needed. It is also important to note that “by chemical oxidation” is a product by process step and is not a determining factor in a product claim. MPEP 2121 states that prior art is presumed to be operable/enabling and a reference is presumed operable until applicant provides evidence showing that the subject matter was not known at the relevant time. Further, an application nor a reference need not teach what was known to those skilled in the art before filing (“A patent need not teach, and preferably omits, what is well known in the art”, MPEP 2164.01). Ren et al. (CN 1836738 A, Sep. 27, 2006, machine translation) teaches modifying polymer surfaces such as polyolefins by introducing hydroxyl groups via surface oxidation which is evidence that such a step was known in the art prior to the Clevenger reference. In other words, a skilled artisan, at the relevant time, would have understood in the reviewing of Clevenger that modifying polymer surfaces such as polyolefins by introducing hydroxyl groups via surface oxidation was known. For these reasons, Applicant’s arguments are found unpersuasive.
Said 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4, 6, 7, 9, 14, 20, 46, 48 and 57 stand rejected under 35 U.S.C. 103 as being unpatentable over Clevenger et al. (US 2010/0215643 A1, Aug. 26, 2010, hereafter as “Clevenger”) in view of Koontz et al. (USPN 5,369,012, Nov. 29, 1994, hereafter as “Koontz”).
The claimed invention is drawn to a construct comprising: a) a polymer surface oxidized or aminated to introduce chemically accessible, reactive oxy, oxo, carbonyl, carboxylic acid, carboxylate or amino functional groups reactive with inorganic alkoxides; and b) an inorganic oxide adhesion layer chemically bonded to said reactive functional groups of said polymer surface, said inorganic oxide adhesion layer comprising surface oxide groups; and c) a self-assembled monolayer of phosphonates (SAMP) bonded to the surface of said inorganic oxide adhesion layer; wherein the SAMP further comprises an anti-infective agent or an antithrombogenic agent covalently bonded thereto.
Regarding instant claim 1, Clevenger teaches functionalization of substrates that allow for binding of anti-infective agents to said functionalized surfaces such that said surfaces have been modified to have anti-infective properties (abstract, [0002], [0053]-[0055] and [0063]-[0064]; Fig. 1; Examples). Clevenger teaches an activated surface comprising chemically accessible, reactive functional groups and an inorganic alkoxide adhesion layer chemically bonded to said reactive functional groups ([0031]-[0033]; Examples). Clevenger teaches the particular surface reactive functional groups, hydroxyl (-OH) and amino (-NH) groups ([0031). Clevenger teaches that the surfaces can be a polymer, e.g., polysiloxanes, polyethylene (a polyolefin) and polypropylene (a polyolefin) ([0013]-[0015] and [0017]; claim 30). Clevenger teaches the inclusion of a self-assembled monolayer composed of phosphonates wherein said layer is covalently bonded to functional groups ([0040], [0046] and [0048]). Clevenger also teaches a self-assembled phosphate monolayer bonded to a native oxide surface, wherein the self-assembled phosphonate monolayer is operable to bond an anti-infective agent (claim 67). Clevenger further teaches covalent bonding of the phosphonate film to the anti-infective agents ([0016]-[0017] and [0040]).
Clevenger is silent to an oxidized or aminated polymer surface.
Koontz teaches treating polymer surfaces with oxidizing plasma species and then grafting compatibilizing compounds to the treated surface (col. 5, lines 7-13). Koontz also teaches that the graft substrate may be used as a base for succeeding grafts or as an adhesive layer for proteins or living cells (col. 5, lines 13-15). Koontz teaches that the polymer substrate may be treated with a substantially uniform concentration of atomic oxygen or hydroxyl radicals and that said treated surface may be used to enhance surface adsorption of proteins or other bioactives, enhance surface adherence of cells or as a base for further surface compatibilizing (col. 5, lines 16-26). Koontz teaches that the substrates can be utilized in the body (col. 6, lines 3-7).
Clevenger and Koontz are both drawn to polymer surface treatments that allow further attachment of bioactives, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to include an oxidized or aminated polymer surface in the invention of Clevenger as suggested by Koontz with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Koontz teaches that the oxidized polymer surface can be used as a base for succeeding grafts or as an adhesive layer for bioactives. Additionally, Clevenger teaches that alkoxides react with -OH or -NH groups on the substrate to form an alkoxide adhesion layer ([0013]-[0015]). Thus, one of ordinary skill in the art would have reasonably expected an oxidized polymer having -OH groups react with alkoxides to form an alkoxide adhesion layer thereon to effectively provide an adhesive layer and additional functional groups to bind to bioactives.
Regarding instant claim 4, Clevenger teaches the particular polymer substrates, polysiloxanes, polyethylene (a polyolefin) and polypropylene (a polyolefin) (claim 30).
Regarding instant claim 6, the claim recites the limitation, “wherein said surface reactive functional groups are produced by chemical oxidation”. It is noted that claim 6 is deemed a product-by-process claim due to the limitation, “produced by chemical oxidation” and as such, determination of patentability is based on the product itself, not by the method in which it is made. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process (MPEP 2113). It is further noted that the functional groups recited in claim 6 are not required because parent claim 1 recites said functional groups in addition to “amino” functional groups in the alternative. Clevenger, as discussed above, teaches said amino functional groups and as such meets the limitations of the claim.
Regarding instant claim 7, said claim depends from claim 6. As explained above, claim 6 (and its dependent claim 7) is deemed a product-by-process claim due to the limitation, “produced by chemical oxidation” and as such, determination of patentability is based on the product itself, not by the method in which it is made. Claim 7 does not further limit the product itself, therefore Clevenger reads on said claim. It is further noted that Clevenger additionally teaches the particular oxidizing agents, ozone and permanganate as well as oxygen and peroxides ([0035]).
Regarding instant claim 9, Clevenger teaches alkoxides of the particular metals, Ti, Zr, Al, Nb, Ta, Sn and V ([0055]).
Regarding instant claim 14, Clevenger teaches the particular phosphonate, 11-hydroxyundecylphosphonic acid ([0104]) which has the claimed phosphonic acid structure wherein R is a substituted alkyl.
Regarding instant claim 20, Clevenger teaches the particular anti-infective agents, chlorhexidine, quaternary ammonium cations (e.g., benzalkonium chloride), quaternary ammonium dendrimers, and cationic species ([0035] and [0038]).
Regarding instant claim 46, Clevenger teaches the particular anti-infective agents, copper and silver ([0073] and [0097]; claims 7 and 8).
Regarding instant claim 48, Clevenger, as discussed above, teaches the particular polymers, polysiloxanes, polyethylene (i.e., a polyolefin) and polypropylene (i.e., a polyolefin) ([0013]-[0015] and [0017]; claim 30). The limitations regarding the functional groups produced by chemical oxidation are considered product by process limitations. Determination of patentability is based on the product itself, not by the method in which it is made. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process (MPEP 2113). Furthermore, Clevenger teaches surfaces with acidic protons such as -OH or -NH groups react with Group IV alkoxides ([0031]). Clevenger also teaches that “any polymer can be functionalized” including polyethylene ([0054]). In order to introduce an -OH group into a polymer such as polyethene, an oxidation step must take place. Thus, while Clevenger teaches polymers that inherently contain reactive functional groups, e.g., -OH, Clevenger also teaches polymers that must be activated/functionalized. Clevenger’s teachings imply that if the functional groups are not inherently present, an activation/oxidation step must take place in order for functional groups to be introduced and bond to the alkoxides. In the instance of a polyethylene, when activated/oxidized, an -OH group will be added to each cleavage site and glycol is necessarily created. MPEP 2112.01(I) states,
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433.
Regarding instant claim 57, Clevenger, as discussed above, teaches surface oxides ([0014]-[0016]; claim 67), wherein the surface oxide comprises alkoxide groups ([0014]-[0015], [0033] and [0046]).
Thus, the combined teachings of Clevenger and Koontz render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 10/14/2025, regarding the 103 rejection over Clevenger and Koontz have been fully considered but they are not persuasive.
Applicant argues that Claim 1 has been amended to clarify that the reactive functional groups are introduced onto the polymer surface by chemical oxidation or amination. Remarks, page 8.
In response, it is respectfully submitted that claim 1 recites, “a polymer surface oxidized or aminated to introduce chemically accessible, reactive oxy, oxo…”. However, the limitation “chemical oxidation” is not recited until claim 6. Thus, independent claim 1 does not recite “chemical oxidation” as applicant contends. Further, “produced by chemical oxidation” is considered a product by process limitation. The claims are directed to a product and determination of patentability is based on the product itself, not by the method in which it is made. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process (MPEP 2113). As discussed in the rejection above, the structural limitations of the claimed construct are suggested by the combined teachings of Clevenger and Koontz and, as such, meet the limitations of the claimed invention.
Applicant argues that Koontz discloses the use of silane coupling agents following oxidation of a polymer surface which form Si-O-Si linkages between the surface and the silane layer. Applicant asserts that such siloxane films are hydrolytically unstable under physiology condition, leading to loss of surface functionality over time. Applicant asserts that the present invention employs hydrolysis of a metal alkoxide to form a covalently bonded inorganic oxide adhesion layer characterized by a Metal-O-Metal network. Applicant asserts that this adhesion layer provides a robust and hydrolytically stable interface that securely anchors a phosphonate self-assembled monolayer and covalently bound active agents resulting in superior hydrolytic stability relative to silane-based systems. Remarks, pages 8-9.
In response, it is respectfully submitted that Koontz is relied upon for its teaching of treating polymer surfaces with oxidizing plasma species that can then be grafted with compatibilizing compounds to the treated surface (col. 5, lines 7-13). Koontz teaches that a polymer substrate may be treated with a substantially uniform concentration of atomic oxygen or hydroxyl radicals and that said treated surface may be used to enhance surface adsorption of proteins or other bioactives, enhance surface adherence of cells or as a base for further surface compatibilizing (col. 5, lines 16-26). In other words, Koontz is relied upon for the general treatment of polymer surfaces via oxidation to introduce hydroxyl groups in order to graft compounds to the treated surface. Koontz is not relied upon for the particular Si-O-Si linkages contrary to applicant’s assertions. Thus, applicant’s argument is inapplicable to the merits of the rejection.
Applicant argues that Koontz used an atomic oxygen reactor to oxidize polymer membranes to create active surfaces suitable for subsequent silane coupling. Applicant asserts that oxidation is carried out to such an extent that the polymer surface is largely converted to inorganic silicon dioxide, water and carbon dioxide. Applicant’ asserts that that the process of the instant application does not alter the polymer surface so drastically. Applicant asserts that the polymer remains organic in nature and is only lightly oxidized to introduce reactive oxygen functionalities. Remarks, page 9.
In response, it is respectfully submitted that the claims do not require any particular degree of oxidation and, as discussed above, determination of patentability is based on the product itself, not by the method in which it is made. MPEP 2113 states,
"The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product.
If a structural difference is produced by the method of the prior art versus the method of the claimed invention, it is applicant’s burden to provide evidence establishing an nonobvious difference between the claimed product and the prior art product. No such evidence has been provided. Thus, applicant’s argument is unpersuasive.
Applicant argues that Koontz does not disclose amination of polymer surfaces in the manner recited in the claims. Applicant asserts that Koontz teaches that amine functionality is introduced indirectly, by coupling phosphorylcholine-containing molecules to a silanized surface. Remarks, pages 9-10.
In response, it is respectfully submitted that the claims include open-ended “comprising” language that does not exclude additional unrecited elements (MPEP 2111.03(I)). Thus, the claims do not exclude indirect amination. Applicant’s argument is unpersuasive.
Applicant argues that the claimed construct is further non-obvious because one of ordinary skill in the art would not have reasonably expected, based on the cited prior art, that covalently attaching an anti-infective or anti-thrombogenic agent through a SAMP, bonded to an inorganic alkoxide layer on an oxidized or aminated polymer surface, would produce a non-eluting surface upon implantation. Applicant asserts that the Declaration dated 2/28/2025 explains that the multilayer construct exhibits the unexpected property that antimicrobial agents attached to the SAMP remain bound and are not released into the surrounding environment. Applicant also asserts that 2024 soaking experiments confirmed that the antimicrobial agents attached to the SAMP remain bound and were not released. Remarks, page 10.
In response, it is respectfully submitted that the prior art does not teach that the bioactives are released or eluted and applicant has not provided data that the prior art behaves in a different manner (i.e., eluting) than the instant invention (i.e., non-eluting). Arguments presented by the applicant cannot take the place of evidence in the record (MPEP 716.01(c)(II)). Please refer to MPEP 716.02(b) which details the burden on Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, Applicant must establish that differences in results are in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims (MPEP 716.02(d)). Thus, Applicant’s argument is unpersuasive.
For the above reasons, Applicant’s arguments are found unpersuasive. Said rejection is maintained.
Conclusion
All claims have been rejected; no claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CASEY HAGOPIAN whose telephone number is (571)272-6097. The examiner can normally be reached on M-F 9:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached on 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Casey S. Hagopian
Examiner, Art Unit 1617
/CARLOS A AZPURU/Primary Examiner, Art Unit 1617