DETAILED ACTION
Status of the Claims
Claims 9, 13-15, 17 and 19-31 are pending in the instant application and are being examined on the merits in the instant application. Claims 30-31 are newly presented.
Advisory Notice
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All rejections and/or objections not explicitly maintained in the instant office action have been withdrawn per Applicants’ claim amendments and/or persuasive arguments.
Priority
The instant Application was filed 10/22/2021 and claims priority to the U.S. Provisional Application No. 63/104,241 (hereafter ‘241) filed 10/22/2020.
The U.S. effective filing date has been determined to be 10/22/2021, the filing date of the instant Application. The examiner does not find support in ‘241 for the limitation “wherein the bactericidal metal element is incorporated into the columnar microstructure such that the bactericidal metal element is disposed at least partially around or within the columnar microstructure pillars and is accessible through out the pores thereof” (instant claim 9, lines 13-16). Claims 13-15, 17, 19-21 and 30 depend from claim 9, inheriting the aforementioned limitation and thus the same filing date.
The examiner does not find support in ‘241 for the limitation “a bactericidal layer comprising a multilayer structure” (claim 22, line 4) or the limitation “wherein the bactericidal metal element is incorporated into the first portion of the TiN or ZrN
columnar microstructure such that the bactericidal metal element is disposed at least partially around or within the first portion of the TiN or ZrN pillars, and is accessible through out the pores thereof” (claim 22, lines 14-18). Claims 23-29 and 31 depend from claim 9, inheriting the aforementioned limitation and thus the same filing date.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 9, 14-15, 19-22, 24-25 and 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over OSTRUM (US 2013/0344123; published December, 2013) in view of Outten et al. (“Development of Titanium Nitride Fractal Coatings for Cardiac and Neural Electrostimulation Electrodes,” 2014; 57th Annual Technical Conference Proceedings, pp. 33-37); LINK (WO 2019/214992 A1; published 11/14/2019 in German, US 2012/0128782 A1 relied on and cited herein) Samberg et al. (“Biocompatibility analysis of an electrically-activated silver-based antibacterial surface system for medical device applications,” 2013; Journal of Materials Science: Materials in Medicine, Vol. 24, No. 3, pp. 755-760) and FIELDS (US 6,539,252; published March, 2003).
Applicants Claims
Applicant claims an electrode article that is implantable in a subject, the article comprising: an electrode substrate having a surface; a bacterial layer comprising a bactericidal metal element and a titanium nitride (TiN) or zirconium nitride (ZrN) columnar microstructure; wherein the bactericidal metal element comprises copper or silver, wherein the TiN or ZrN columnar microstructure comprises pillars having pores therebetween, and wherein the bactericidal layer is stably adhered to at least on portion of the surface of the electrode substrate; and a power source configured to apply an electrical potential to the bactericidal layer, wherein the bactericidal layer, wherein ions of the bactericidal metal element are released from the composite into the pores of the bactericidal layer in response to the application of electrical potential to the bactericidal layer, and wherein the pores of the bactericidal layer allow for released ions of the bactericidal metal element to diffuse into a bodily fluid which is in contact with the electrode article. (instant claim 9).
Applicant claims an electrode article that is implantable in a subject, the article comprising: an electrode substrate having a surface; a bactericidal layer comprising a multilayer structure comprising: a composite layer comprising a bactericidal metal element and a first portion of a TiN or ZrN columnar microstructure, a TiN or ZrN layer comprising a second portion of the TiN or ZrN columnar microstructure, but without the bactericidal metal element, wherein the bactericidal metal element comprises copper or silver, wherein the TiN or ZrN columnar microstructure formed by the composite layer and the TiN or ZrN layer comprises pillars having pores therebetween, wherein the bactericidal layer is stably adhered to at least one portion of the surface of the electrode substrate; and a power source configured to apply an electrical potential to the bactericidal layer; wherein ions of the bactericidal metal element are released from the composite layer into the pores of the bactericidal layer in response to the application of electrical potential to the bactericidal layer, and wherein the pores of the bactericidal layer allow for released ions of the bactericidal metal to diffuse into a bodily fluid which is in contact with the electrode (new claim 22).
Determination of the scope
and content of the prior art (MPEP 2141.01)
OSTRUM teaches use of silver-containing layers at implant surfaces, “The silver is present in a microparticulate or nanoparticulate form, which exerts antimicrobial activity when bacteria (e.g., in a body fluid) contact the coated surface.” (see whole document, particularly the title & abstract).
Regarding claims 9 and 22 OSTRUM teaches "coatings that contain silver," wherein the silver "exerts antimicrobial activity when bacteria… contact the coated surface" (Abstract), and that articles comprising the coating are implantable in an animal (Claim 1). OSTRUM further teaches that "the surface can also be coated with other substances, such as diamond-like carbon or alumina, either as a discrete layer or intermixed with the silver-containing particles" [emphasis added](Abstract). And further that: “The antimicrobial layer can include or be coated with other materials, such as alumina or diamond-like carbon (DLC). By way of example, these materials can be uniformly mixed, laminated as separate layers (e.g., a porous layer enclosing the antimicrobial layer), or mixed such that the composition varies in different portions of the layer.” [emphasis added]([0013]).
Specifically regarding the multilayer structure including a bactericidal metal element composite layer below a layer without the bactericidal metal element (instant claim 22, lines 4-8), OSTRUM teaches that: “The antimicrobial layer can include or be coated with other materials, such as alumina or diamond-like carbon
(DLC). By way of example, these materials can be uniformly mixed, laminated as separate layers (e.g., a porous layer enclosing the antimicrobial layer), or mixed such that the composition varies in different portions of the layer.” ([0013]). And that: “For instance, use of multiple sources facilitates deposition of discrete layers of different materials, mixing of sputtered materials at the atomic level, or a combination of these.” ([0029]). OSTRUM teaches the embodiment wherein: “The implants described have a coating which includes Ag. In one embodiment, Ag is intermixed with a DLC material, and the mixed material is laid down ( e.g., via simultaneous sputtering from discrete Ag and DLC sputtering cathodes) as a substantially homogenous DLC-Ag matrix. HA [(hydroxyapatite)] can also be co-sputtered with Ag, or with both Ag and DLC to form similarly substantially homogenous matrices. Alternatively, or in addition, discrete layers of one or more of these materials can be laid down in a coating by operating the corresponding sputtering cathode(s) selectively. Thus, for example, a titanium implant having a coating can be made by sputtering substantially only HA onto a titanium surface of
the implant, then sputtering a mixture of Ag and HA to form a mixed Ag-HA layer, then sputtering a mixture of Ag, HA, and DLC to form a mixed Ag-HA-DLC layer, then sputtering a mixture of Ag and DLC to form a mixed Ag-DLC layer, and finally sputtering substantially only DLC to form an outer DLC layer. In such an example, HA (or borosilicate glass used in its place) can serve to anchor the coating to the titanium surface, Ag mixed with the HA and DLC materials can release Ag ions and exert an antimicrobial effect, and DLC can inhibit adhesion of bacteria and other biomaterials to the coated implant.” [emphasis added]([0034]).
OSTRUM further teaches that: “Thin-films, on the order of 10 nm to 10 micrometers thick, can be readily synthesized using sputtering techniques. Sputtered films have several major advantages when compared to films grown using other technologies. Those advantages include excellent adhesion to many substrate materials, outstanding compositional control when deposited from multiple sources, ability to form discrete layers or allow atomic mixing, and the technique is applicable as a deposition method for most materials.” ([0037]).
The example substrates include titanium and stainless steel (Example 1, page 6)(instant claim 14 & 24). OSTRUM teaches coated implants including pacemaker components (e.g., the outer case), nerve-interface electrodes ([0026], [0027])(instant claims 9 & 21, a power source configured to apply an electrical potential to the bactericidal layer).
OSTRUM teaches that: “Ag exhibits bactericidal properties both upon bacterial cells that are in direct contact with an Ag-containing surface and upon bacterial cells that do not directly contact the Ag-containing surface. Without being bound by any particular theory of operation, it is believed that the non-contact bactericidal effect of Ag is mediated by Ag ions.” [emphasis added]([0051]).
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of OSTRUM is that OSTRUM does not expressly teach a columnar microstructure.
Outten et al. teaches that: "Development of Titanium Nitride Fractal Coatings for Cardiac and Neural Electrostimulation Electrodes," (title, see whole document), and particularly, “This work deals with the development of reactively sputtered fractal titanium nitride coatings for use in electrostimulation and recording electrodes. Electrical stimulation of cardiac and nerve tissues is an active area of research. This presentation will focus on the process development and characterization of porous, columnar titanium nitride coatings that exhibit high electrochemically active surface areas. Depositions were conducted in an industrial-scale sputtering system with substrate temperature varying between 25 – 130°C. Low-temperature deposition of high surface area coatings is presented. These coatings are of particular interest for stimulation electrodes where dimensional stability is a concern, for example implantable neural prostheses leads. The coating microstructure was investigated with Focused Ion Beam Microscopy. These results were used to assess the impact of substrate temperature on film porosity and grain size.” [emphasis added](Abstract, page 33). Outten further teaches that these coatings “are used to improve the performance of electrostimulation and recording electrodes for cardiac and neural prostheses and treatments” [emphasis added](Introduction, page 33)(instant claim 1, An electrode article that is implantable in a subject, the article comprising: an electrode substrate having a surface […] wherein the columnar microstructure comprises pillars having pores therebetween”; instant claims 11-12 - metal nitride, titanium nitride).
Outten et al. teaches that: “This work has shown that fractal TiN coatings can be deposited by DC magnetron sputtering […].” (p. 36, col. 2, lines 1-2), which is consistent with the disclosure of OSTRUM teaching the advantages of sputtering techniques – “Sputtered films have several major advantages when compared to films grown using other technologies.” ([0037]).
OSTRUM teaches that the silver coating may comprise additional layers (Abstract), and that the coating may be applied to pacemakers (Paragraph [0018]), and while Outten et al. teaches that the titanium nitride coating may be applied to devices for cardiac electrostimulation, and that titanium nitride “is an ideal material for [electrostimulation] applications due to its electrical conductivity, chemical stability, and biocompatibility” (Introduction, page 33), one of ordinary skill in the art at the time of instant filing would be motivated to combine the teachings of OSTRUM and Outten et al. because OSTRUM teaches a coating that may be applied to a pacemaker, and Outten et al. teaches a coating that is beneficial for electrostimulation. Such a combination would result in a composite coating that is antibacterial, with high conductivity, chemical stability, and biocompatibility with the silver composite layer adhering over the surface and the columnar layer adhering to the silver composite layer. The adhering would take place due to the coating procedures including sputtering.
Furthermore, the silver coating of OSTRUM and the titanium nitride coating of Outten et al. are construed to be equivalents known in the art to be beneficial for coating implants. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (MPEP § 2144.06). Thus, it is obvious to combine them to form a coating suitable for an implant.
OSTRUM teaches that the silver is deposited via a sputter deposition technique (Example 1, page 6) and that “[s]puttering of Ag is simple with a direct current (DC) power supply connected to a DC magnetron cathode” (Paragraph [0038]). OSTRUM further teaches that “[b]y mixing reactive gases (e.g., oxygen containing gases such as O2 and nitrogen containing gases such as N2) during deposition, the dissolution rate can be… modified” (Paragraph [0055]) and that “[t]his understanding provides a technique for selecting the dissolution rate and the rate of bactericidal action of the coatings” (Paragraph [0056]). Outten et al. teaches that “[f]ractal TiN films were deposited using DC reactive magnetron” (Experimental Procedures, page 33) and that “depositions were carried out in an Ar and N2 gas mixture” (Surface Morphology, page 34). It is obvious to use the method disclosed by OSTRUM and Outten et al. to deposit the coating layers disclosed therein. Thus, an electrode article produced via known methods resulting in a product of claims 9 and 22 are obvious.
Outten et al. teaches "titanium nitride coatings for use in electrostimulation and recording electrodes," wherein the coatings are "porous, columnar titanium nitride coatings that exhibit high electrochemically active surface areas" (Abstract, page 33). Outten et al. further teaches that these coatings “are used to improve the performance of electrostimulation and recording electrodes for cardiac and neural prostheses and treatments” (Introduction, page 33).
OSTRUM teaches that the silver coating may comprise additional layers (Abstract), and that the coating may be applied to pacemakers (Paragraph [0018]), while Outten et al. teaches that the titanium nitride coating may be applied to devices for cardiac electrostimulation, and that titanium nitride “is an ideal material for [electrostimulation] applications due to its electrical conductivity, chemical stability, and biocompatibility” (Introduction, page 33). Additionally, OSTRUM teaches that "the surface can also be coated with other substances, such as diamond-like carbon or alumina, either as a discrete layer or intermixed with the silver-containing particles" [emphasis added](Abstract). And further that: “The antimicrobial layer can include or be coated with other materials, such as alumina or diamond-like carbon (DLC). By way of example, these materials can be uniformly mixed, laminated as separate layers (e.g., a porous layer enclosing the antimicrobial layer), or mixed such that the composition varies in different portions of the layer.” [emphasis added]([0013]). One of ordinary skill in the art before the time of instant filing would be motivated to combine the teachings of OSTRUM and Outten et al. because OSTRUM teaches a coating that may be applied to a pacemaker, and Outten et al. teaches a coating that is beneficial for electrostimulation. Such a combination would result in composite and/or a multilayer coating that is antibacterial, with high conductivity, chemical stability, and biocompatibility.
The silver coating of OSTRUM and the titanium nitride coating of Outten et al. are construed to be equivalents known in the art to be beneficial for coating implants. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (MPEP § 2144.06). Thus, it is obvious to combine them to form a coating suitable for an implant.
Furthermore, because OSTRUM and Outten et al. both disclose that the coatings may be applied to pacemakers (OSTRUM: [0018]) and “electrodes for cardiac and neural prostheses treatments” (Outten et al., Introduction, page 33), it is obvious that the combination of these coatings could be applied to components of a pacemaker, which would inherently include an electrode.
LINK teaches an anti-microbial implant coating (title, [0001], see whole document), and particularly teaches that: The object of the present invention was therefore to provide a coating for an implant surface that prevents an infection in situ. The object of the invention was in particular to provide a coating for an implant surface that counteracts the colonisation of pathogens […].” ([0006]). LINK teaches that: “The invention thus provides a coating for an implant component, in particular a component of a spinal implant, said coating being a ceramic titanium nitride coating having an at % content of 5 to 30 at % of Ag in addition to an at % content of Ti and an at % content of N.” ([0008]). And that: “Such a content of silver can prevent an infection caused by pathogens. An antimicrobial effect against Staphylococcus epidermidis has in particular been found.” ([0009]). And further that: “Owing to its resistance, the ceramic titanium nitride coating with a silver content, i.e. the titanium nitride/silver coating, is particularly suitable for structural implants that support or replace parts of the skeleton when they have been introduced into the body of a patient.” ([0011]).
LINK teaches that: “The present invention furthermore provides a method for applying a coating to an implant component, which comprises the steps of providing an implant component to be coated […] providing at least one Ti target and at least one Ag target, and evaporating the at least one target in an atmosphere containing at least nitrogen, and simultaneously coating the implant component with the evaporated metal of the at least one target.” ([0029]). And that: “This method allows a simultaneous coating with titanium nitride and silver to form the titanium nitride/silver coating. Simultaneous coating ensures that silver is exposed on the surface of the coating and that the infection-inhibiting effect of the coating can thus unfold. Furthermore, by selecting the number of the respective targets of the coating components, the at % content can be adjusted at least in its order of magnitude to the desired composition of the coating.” [emphasis added]([0030]). And further that: “As an alternative or in addition to adjusting the composition of the coating via the number of respective targets, at least one target having a predetermined ratio of titanium and silver can be provided.” ([0031]).
Regarding claims 19 and 27, as discussed above for claims 9 and 22, it is obvious that the coatings could be applied to a pacemaker, which would inherently comprise a power source. Outten et al. teaches the electrochemical properties of the TiN-coated substrate at voltages ranging from -0.8 to +0.8 V (Fig. 3, page 35). A person of ordinary skill in the art would have a reasonable expectation of success that the optimal electrical potential for a coating that comprises TiN would fall somewhere in that range, and a person of ordinary skill in the art, through routine optimization, could determine the optimal electrical potential to maximize the efficiency of the electrostimulation device.
Additionally, FIELDS teaches “A method and apparatus for destroying blood borne pathogens is disclosed which utilizes a low intensity direct current to generate positive particles from various metals which destroy viral pathogens.” (Abstract). And that: “As will be discussed below, the power supply 110 supplies a low intensity direct current to the electrode 35. Because the electrode 35 releases silver cations, there is a chemical reaction that occurs on the surface of the electrode involving silver and oxygen that results in a nonconductive oxide on its surface. Over the treatment period, this oxide increases the surface resistance on the electrode 35. This increased resistance requires that the power supply 110 increase the voltage applied to the electrode 35 to produce the same number of silver ions throughout the treatment period. Thus in a preferred embodiment, the power supply 110 adjusts its voltage to maintain the proper current level and hence voltage level. However, at 0.88 volts and higher, the oxide can be forced off of the electrode, which could cause blood clots, stroke and the like. Therefore, a preferred embodiment of the present invention has a voltage limit of 0.86 volts. If the power supply 110 is required to supply more than 0.86 volts, it will shut down.” (paragraph bridging cols. 8-9). FIELDS further teaches the electrode comprises silver, copper and platinum “In a preferred embodiment, the electrode 35 is an alloy comprised of 97.8 percent silver, 0.2 percent copper, and 2.0 percent platinum.” (col. 7, lines 38-41; claims 9-10)(instant claims 9, 21, 22 & 29).
Regarding claims 20 and 28, OSTRUM teaches coatings that may be applied to objects implanted in animals (Claim 1), that they may be applied to devices such as pacemakers. Outten et al. teaches that the coating may be applied to “electrostimulation and recording electrodes for cardiac and neural prostheses and treatments” (Introduction, page 33). While they do not explicitly recite humans, devices such as these are often developed and implanted into humans. A person of ordinary skill in the art would immediately recognize that these devices can be implanted into humans, and would have a reasonable expectation of success that if the article of claim 9 were implanted into a human, it would function as designed. Additionally, note that claim 20 is to an article and not to a method of using the article where human would be more relevant. Nonetheless, the article of OSTRUM and Outten et al. is capable of use in humans.
Samberg et al. teaches that: “The costs associated with the treatment of medical device and surgical site infections are a major cause of concern in the global healthcare system. To prevent transmission of such infections, a prophylactic surface system that provides protracted release of antibacterial silver ions using low intensity direct electric current (LIDC; 28 lA system current at 6 V) activation has been recently developed.” (abstract, see whole document).
Samberg et al. teaches that: “the objective of this study was to assess the biocompatibility of the prophylactic surface system that uses electrical activation as a delivery mechanism for antibacterial Ag+. Specifically, investigations of the cytotoxicity to human epidermal keratinocytes (HEK), human dermal fibroblasts (HDF) and human osteoblasts (OST), and the antibacterial efficacy to Escherichia coli and S. aureus of electrically liberated Ag+ from interdigitated silver ink electrodes at specific current and voltage levels within a range of electrical parameters previously determined to kill the bacterial strains were conducted” (p. 756, col. 2, lines 9-19). And that: “The antimicrobial surface system consists of an interdigitated pattern of alternate electrically charged positive and negative silver-based electrodes separated by an electrically resistive insulation, and activated by LIDC. The system functions on the principle of oligodynamic iontophoresis; when the surface is in contact with any conducting liquid, the LIDC in the system causes the release and diffusion of antibacterial Ag+ from the silver anodes into the liquid medium. Surfaces in healthcare environments (e.g. medical implants, surgical tools) are frequently exposed to bacteria in the form of aqueous liquid media such as blood or other body fluids. In presence of such infected media on the surface, the resulting electrically stimulated Ag+ trigger the system to self-sterilize. This surface system design and its working principle are explained in more details elsewhere.” (p. 756, col. 2, §2.1, 1st paragraph).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
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 teachings of OSTRUM and Outten et al. because OSTRUM teaches a coating that may be applied to a pacemaker, and Outten et al. teaches a coating that is beneficial for electrostimulation, and a combination would result in composite multi-layered coating that is antibacterial, with high conductivity, chemical stability, and biocompatibility with the silver layer adhering over the surface and the columnar layer adhering to the silver layer, and further to modify the coatings to actively release silver ions, by electrical stimulation as suggested by FIELDS, for their antimicrobial effect of self-sterilizing without causing toxicity in vivo, as suggested by Samberg et al. to reduce the high costs associated with surgical treatments, the composite coating of TiN and silver being suggested by LINK for antimicrobial implants. Furthermore, the silver coating of OSTRUM and the titanium nitride coating of Outten et al. are construed to be equivalents known in the art to be beneficial for coating implants. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (MPEP § 2144.06). Thus, it is obvious to combine them to form a coating suitable for an implant.
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 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, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Claims 13, 17, 23 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over OSTRUM in view of Outten et al.; LINK; Samberg et al. and FIELDS, as applied to claims 9, 14-15, 19-22, 24-25 and 27-29 above, and further in view of Saubade et al. (“Effectiveness of titanium nitride silver coatings against Staphylococcus spp. in the presence of BSA and whole blood conditioning agents” 2019; ELSEVIER; International Biodeterioration & Biodegradation, Vol. 141, pp. 44-51) and Whitehead et al. (“Surface topography and physicochemistry of silver containing titanium nitride nanocomposite coatings,” 2010; Journal of Vacuum Science and Technology B, Vol. 28, No. 1, pp. 180-187).
Applicants Claims
Applicant claims an electrode article that is implantable in a subject, the article comprising: an electrode substrate having a surface; a bacterial layer comprising a bactericidal metal element and a titanium nitride (TiN) or zirconium nitride (ZrN) columnar microstructure, as discussed above.
Applicant claims an electrode article that is implantable in a subject, the article comprising: an electrode substrate having a surface; a bactericidal layer comprising a multilayer structure comprising: a composite layer comprising a bactericidal metal element and a first portion of a TiN or ZrN columnar microstructure, as discussed above. Applicant further claims the amount of the bactericidal metal element ranges from 5% to 18% (mol/mol) based on a total amount of metal elements in the bactericidal layer (instant claims 13 & 23). And wherein the bactericidal layer is synthesized by co-deposition of the bactericidal metal element and Ti onto at least a portion of the substrate’s surface under a partial pressure of Nitrogen (instant claims 17 and 26).
Determination of the scope
and content of the prior art (MPEP 2141.01)
OSTRUM teaches use of silver-containing layers at implant surfaces, as discussed above and incorporated herein by reference.
Outten et al. teaches titanium nitride coatings for use in electrostimulation and recording electrodes, and that the coatings are porous, columnar titanium nitride coatings that exhibit high electrochemically active surface areas, a discussed above and incorporated herein by reference.
LINK teaches an anti-microbial implant coating by simultaneous deposition of titanium nitride and silver, as discussed above and incorporated herein by reference.
Samberg et al. teaching that the costs associated with the treatment of medical device and surgical site infections are a major cause of concern in the global healthcare system, as discussed above and incorporated herein by reference.
FIELDS teaches a method and apparatus for destroying blood borne pathogens is disclosed which utilizes a low intensity direct current to generate positive particles from various metals which destroy viral pathogens, as discussed above and incorporated herein by reference.
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of OSTRUM and Outten et al. is that these references do not expressly teach the amount of Silver is 5% to 18% (mol/mol) based on a total amount of metal elements in the bactericidal layer.
Regarding claims 17 and 26, these claim are construed to be product-by-process claims. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. 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." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (MPEP § 2113(I)). Additionally, LINK teaches co-depositing (simultaneous coating with titanium nitride and silver – [0030]), as discussed above and incorporated herein by reference.
Nonetheless, OSTRUM teaches that the silver is deposited via a sputter deposition technique (Example 1, page 6) and that “[s]puttering of Ag is simple with a direct current (DC) power supply connected to a DC magnetron cathode” (Paragraph [0038]). OSTRUM further teaches that “[b]y mixing reactive gases (e.g., oxygen containing gases such as O2 and nitrogen containing gases such as N2) during deposition, the dissolution rate can be… modified” (Paragraph [0055]) and that “[t]his understanding provides a technique for selecting the dissolution rate and the rate of bactericidal action of the coatings” (Paragraph [0056]). Outten et al. teaches that “[f]ractal TiN films were deposited using DC reactive magnetron” (Experimental Procedures, page 33) and that “depositions were carried out in an Ar and N2 gas mixture” (Surface Morphology, page 34). It is obvious to use the method disclosed by OSTRUM and Outten et al. to deposit the coating layers disclosed therein. Thus, a product produced via the methods of claims 16 and 17 are obvious.
Regarding claim 13 and 17, Saubade et al. teaches “medical grade stainless steel substrata… coated with… titanium nitride/silver (TiN/14.94 at %Ag or TiN/19.04 at %Ag)” (Abstract, page 44, results/discussion), and that these surfaces are antibacterial (Fig. 3, page 48). These substrates comprise 14.94% or 19.04% silver (Substrate, page 45). Saubade et al. teaches that: “To the authors knowledge, the effect of a conditioning film on bacterial retention and antimicrobial activity on TiNAg, coatings, i.e., nanocomposite coatings containing silver particles in a titanium nitride matrix, has not been previously described.” [emphasis added](p. 45, col. 1, lines 12-16). And that: “Coatings were deposited onto the stainless steel coupons, (titanium nitride (TiN), titanium nitride with 14.94% silver (TiN/14.94 at.%Ag) and 19.04% (TiN/19.04 at.%Ag) using an adapted magnetron sputtering method (Whitehead et al., 2010a,b).” [emphasis added](p. 45, col. 1, §2.1).
Whitehead et al. teaches that: “Silver has also long been thought to have antimicrobial and anti-inflammatory properties being effective against a broad range of yeast, fungi, viruses, and Gram-negative and Gram positive bacteria (including methicillin-resistant Staphylococcus aureus). Combining the properties of titanium nitride with the inherent antimicrobial nature of silver particularly when present in nanocrystalline form, opens up a number of novel applications for TiN/Ag nanocomposite films in, for example, the biomedical or food processing industries
where surfaces that are durable, safe, readily clean able, and resistant to microbial contamination are required.” (p. 180, col. 2, lines 5-16). Whitehead et al. teaches that: “Titanium nitride (TiN) is a hard, wear-resistant coating material, which is widely applied to components operating in an abrasive wear environment. When codeposited with silver, the coating forms a nanocomposite structure consisting of nanoparticles of silver embedded in a TiN matrix. TiN/Ag coatings were deposited by cosputtering onto bright annealed stainless steel substrates. By control of the target powers, the silver content of the films was varied in the range of 0–16.7 at. %.” (abstract, see whole document)(instant claims 13, 17, 23, and 26).
Whitehead et al. teaches that: “To combine the properties of titanium nitride together with silver in a coating, the physical vapor deposition technique of closed field unbalanced magnetron sputtering has been used. TiN and Ag are immiscible, thus when deposited together by cosputtering from two targets, the coating forms a structure that consists of a matrix of TiN surrounding nanoparticles of silver. This occurs since during deposition titanium has a very strong affinity for nitrogen whereas silver nitride is unstable. Novel titanium nitride/silver (TiN/Ag) nanocomposite coatings were therefore deposited and analyzed using a range of surface analytical techniques to determine surface roughness, topography, and physicochemical characteristics in order to assess the effect of increased silver concentration on surface properties.” (p. 181, col. 1, 4th paragraph). Whitehead et al. teaches that: “Deposition took place in Ar–N2 atmospheres at 0.24 Pa with an Ar flow volume of 15 SCCM (SCCM denotes cubic centimeter per minute at STP). The chamber pressure was 0.23 Pa before N2 was introduced.” (p. 181, col. 2, lines 6-9)(instant claim 13).
One of ordinary skill in the art at the time of instant filing would be motivated to combine the teachings of OSTRUM, Outten et al., and Saubade et al., as OSTRUM teaches antibacterial coatings comprising silver, Outten et al. teaches the benefits of coatings comprising titanium nitride, and Saubade et al. teaches an appropriate ratio of silver to titanium nitride. Such a combination would result in an effective antibacterial composition as recognized by Saubade et al. See MPEP 2144.05 regarding obviousness of ranges and close values.
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
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 utilize a bactericidal effective amount of silver biocide in the implant coating suggested by OSTRUM and Outten et al., to actively release silver ions, by electrical stimulation as suggested by FIELDS, the composite coating of TiN and silver being suggested by LINK for antimicrobial implants, as discussed above, the bactericidal amount being in the range of ~14-19% silver, as suggested by Saubade et al. in order to effectively mitigate/prevent infection in a biocide coated implant, as Saubade et al. teaches an appropriate ratio of silver to titanium nitride, such a combination would result in an effective antibacterial composition as recognized by Saubade. See MPEP 2144.05 regarding obviousness of ranges.
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 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, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Claims 30 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over OSTRUM in view of Outten et al.; LINK; Samberg et al. and FIELDS, as applied to claims 9, 14-15, 19-22, 24-25 and 27-29 above, and further in view of NEUMANN (US 2013/0252021 A1; published September, 2013).
Applicants Claims
Applicant claims an electrode article that is implantable in a subject, the article comprising: an electrode substrate having a surface; a bacterial layer comprising a bactericidal metal element and a titanium nitride (TiN) or zirconium nitride (ZrN) columnar microstructure, as discussed above. Applicant further claims the bactericidal metal element comprises copper, and wherein the copper is distributed within and throughout the columnar microstructure of the composite coating (instant claim 3), and wherein the copper is distributed within and throughout the first portion of the TiN or ZrN columnar microstructure (instant claim 31).
Determination of the scope
and content of the prior art (MPEP 2141.01)
OSTRUM teaches use of silver-containing layers at implant surfaces, as discussed above and incorporated herein by reference.
Outten et al. teaches titanium nitride coatings for use in electrostimulation and recording electrodes, and that the coatings are porous, columnar titanium nitride coatings that exhibit high electrochemically active surface areas, a discussed above and incorporated herein by reference.
LINK teaches an anti-microbial implant coating by simultaneous deposition of titanium nitride and silver, as discussed above and incorporated herein by reference.
Samberg et al. teaching that the costs associated with the treatment of medical device and surgical site infections are a major cause of concern in the global healthcare system, as discussed above and incorporated herein by reference.
FIELDS teaches a method and apparatus for destroying blood borne pathogens is disclosed which utilizes a low intensity direct current to generate positive particles from various metals which destroy viral pathogens, as discussed above and incorporated herein by reference.
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of OSTRUM and Outten et al. is that these references do not expressly teach the bactericidal metal comprises copper.
NEUMANN teaches antibacterial coating for an implant (title, see whole document).
NEUMANN teaches that: “It is generally known that silver has a high antibacterial activity. It is also already described in the prior art to use silver in a coating for implants.” ([0002]). And that: “The cytotoxicity of silver ions that has been observed even with such low concentrations corresponds to the fact that silver does not play a role in the metabolism of the cell; silver is not part of the so-called essential trace elements in the human organism. The intake of low doses of silver, as well as a release from silver surfaces occurring over a longer period of time may lead to permanent cell damage.” ([0004]).
NEUMANN teaches that: “It is also known that copper has an antibacterial
activity, which, however, is lower than the antibacterial activity of silver.” ([0005]).
NEUMAN teaches that: “the invention provision is made for an antibacterial coating for an implant, the coating being characterized in that it contains copper. The
invention is based on the finding that an antibacterial activity can be obtained by adding copper to the coating, without the mechanical properties of the coating being substantially affected thereby, […]. It is taken into consideration here that even comparatively small amounts of copper have a sufficient antibacterial activity, although copper as such has a lower antibacterial activity than silver. The cytotoxic effect of silver, on the other hand, starts at markedly lower concentrations than in the case of copper.” ([0008]). And that: “The antibacterial activity allows the activity of bacteria which reach the implant or are transported into the wound in an undesirable manner during the insertion of the implant into the body, or are already present in the body due to an infection, to be considerably reduced.” ([0009]). And further that: “An exemplary method of coating implants with the antibacterial coating will now be described below. The implants are provided with a coating consisting of a multilayer system of TiN and Cu in a plurality of underlayers. The proportion of copper in the coating is sufficiently high so as to develop an antibacterial activity.” ([0027]).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
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 utilize a bactericidal effective amount of silver biocide in the implant coating suggested by OSTRUM and Outten et al., to actively release silver ions, by electrical stimulation as suggested by FIELDS, the composite coating of TiN and silver being suggested by LINK for antimicrobial implants, as discussed above, and to combine/substitute the silver for copper, as suggested by NEUMANN for reducing infection associated with implants.
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 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, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Response to Arguments:
Applicant's arguments filed 06/16/2026 have been fully considered but they are not persuasive.
Applicant argues that: “Claim 9 has been further amended to recite "composite coating" for clarification. As described in paragraph [000122] of the application as filed, "composite coating" means a "substance compris[ing] at least two constituent materials that are not discretely divided into two layers." As such, one of ordinary skill in the art would understand that the term "composite coating," as used herein, excludes multilayer structures comprising discrete layers stacked on top of each other.” (p. 7, last paragraph). And further that: “As detailed elsewhere herein, the definition of the features of "composite coating" as recited in claim 9 excludes multilayer structures in which discrete layers are stacked on top of each other (specification, paragraph [000122]). Furthermore, the features that the bactericidal metal element is disposed at least partially around or within the TiN or ZrN pillars clearly demonstrate that the bactericidal metal element is incorporated into the columnar microstructure such that the composite coating is a single, inseparable layer comprising the TiN or ZrN, as well as the bactericidal metal element.” (paragraph bridging pp. 9-10).
In response the examiner argues that the claims are open-ended (“the article comprising: […] a bactericidal layer comprising a composite coating comprising […].” MPEP §2111.03 makes clear that: The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. Therefore, the claims clearly do not exclude multilayer structures in which discrete layers are stacked on top of each other. Applicant’s position that: “the bactericidal metal element is incorporated into the columnar microstructure such that the composite coating is a single, inseparable layer comprising the TiN or ZrN, as well as the bactericidal metal element.” is unclear as the release (i.e. the separation) of the bactericidal metal is clearly the intended use of the disclosed and claimed bactericidal coating compositions. OSTRUM teaches that "the surface can also be coated with other substances, such as diamond-like carbon or alumina, either as a discrete layer or intermixed with the silver-containing particles" [emphasis added](Abstract). And further that: “The antimicrobial layer can include or be coated with other materials, such as alumina or diamond-like carbon (DLC). By way of example, these materials can be uniformly mixed, laminated as separate layers (e.g., a porous layer enclosing the antimicrobial layer), or mixed such that the composition varies in different portions of the layer.” [emphasis added]([0013]).
Applicant argues that: “Outten describes titanium nitride fractal coatings for cardiac and neural electrostimulation electrodes (Outten, Title and Abstract). The coatings of Outten comprise a TiN film with TiN pillars (Fig. 1 of Outten), but no bactericidal elements.” (p. 10, 5th paragraph).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that: “The above asserted combination would result in a multilayer structure comprising a columnar layer (which contains no bactericidal metal element) on top of a silver layer (which has no columnar structure). In other words, even if the combination asserted in the Office Action were reasonable (which Applicant does not concede), the resulted structure would nonetheless be wholly different from the composite coating as recited in claim 9, which comprises the TiN/ZrN nitride and Ag/Cu elements all in one single, inseparable layer of columnar microstructure. The asserted combination also does not provide a structure in which an applied electrical potential oxidizes a bactericidal metal element positioned in recessed, pore-accessible regions of a nitride columnar microstructure to provide controlled ion release.” (paragraph bridging pp. 10-11).
In response the examiner argues that: OSTRUM teaches that "the surface can also be coated with other substances, such as diamond-like carbon or alumina, either as a discrete layer or intermixed with the silver-containing particles" [emphasis added](Abstract). And further that: “The antimicrobial layer can include or be coated with other materials, such as alumina or diamond-like carbon (DLC). By way of example, these materials can be uniformly mixed, laminated as separate layers (e.g., a porous layer enclosing the antimicrobial layer), or mixed such that the composition varies in different portions of the layer.” [emphasis added]([0013]). Additionally, LINK teaches a ceramic titanium nitride coating having an at % content of 5 to 30 at % of Ag, wherein the titanium nitride and silver are simultaneously coated onto the surface of an medical implant ([0008], [0030]). Additionally, Saubade et al. teaches that: “To the authors knowledge, the effect of a conditioning film on bacterial retention and antimicrobial activity on TiNAg, coatings, i.e., nanocomposite coatings containing silver particles in a titanium nitride matrix, has not been previously described.” [emphasis added](p. 45, col. 1, lines 12-16). And that: “Coatings were deposited onto the stainless steel coupons, (titanium nitride (TiN), titanium nitride with 14.94% silver (TiN/14.94 at.%Ag) and 19.04% (TiN/19.04 at.%Ag) using an adapted magnetron sputtering method (Whitehead et al., 2010a,b).” [emphasis added](p. 45, col. 1, §2.1). Thus, it would have been prima facie obvious to produce a composite coating by simultaneous coating (i.e. co-deposition) with titanium nitride and silver and/or copper to provide an antimicrobial TiN coating on a medical device such as a medical electrode.
Applicant argues that: “None of the applied references teaches or suggests how to prepare a composite coating that both contains the recited columnar microstructure and have TiN/ZrN, and Ag/Cu all in one single, inseparable layer. Such structural features were not common knowledge at the effective filing date of the present application, either. As such, one of ordinary skill in the art would have been unable to prepare the composite layer of present claim 9, and would have not be motivated to combine or modify the applied references in an attempt to achieve this composite layer.” (p. 11, paragraph second to bottom).
The examiner respectfully disagrees as the prior art clearly suggest co-deposition of titanium nitride (TiN) with antimicrobial silver and/or copper in order to produce an antimicrobial coating, as discussed above. And Outten et al. teaches that: "Development of Titanium Nitride Fractal Coatings for Cardiac and Neural Electrostimulation Electrodes," (title, see whole document), and particularly, “This work deals with the development of reactively sputtered fractal titanium nitride coatings for use in electrostimulation and recording electrodes. […] Depositions were conducted in an industrial-scale sputtering system with substrate temperature varying between 25 – 130°C. Low-temperature deposition of high surface area coatings is presented.(Abstract, page 33). Outten et al. further teaches that: “This work has shown that fractal TiN coatings can be deposited by DC magnetron sputtering […].” (p. 36, col. 2, lines 1-2), which is consistent with the disclosure of OSTRUM teaching the advantages of sputtering techniques – “Sputtered films have several major advantages when compared to films grown using other technologies.” ([0037]).
Applicant further agues that: “As commented above, without the knowledge as how to prepare a single layer comprising all the elements (TiN/ZrN, and Ag/Cu) and having columnar microstructure, one of ordinary skill in the art would have had no reasonable expectation of success to modify or combining Ostrum, Outten, Samberg, and Fields to arrive at the features of present claim 9.” (p. 12, 1st paragraph).
In response the examiner argues that the prior art clearly teaches magnetron sputtering (a PVD process) where the prior art is clearly consistent with Applicants own disclosure. And regarding the columnar microstructure of TiN, Outten et al. clearly teaches this structure, and it would have required no more than an ordinary level of skill in the art to utilize dual targets of titanium and a bactericidal metal such as silver and/or copper for co-deposition, and/or alternating the (composite) coatings with the titanium in a nitrogen atmosphere to produce TiN(Ag,Cu) composite layers.
Applicant argues that: “Without acquiescing to the properness of the above assertions, Applicant respectfully submits that the features newly recited in the present claim 9 (namely that the bactericidal metal element is disposed at least partially around or within the TiN or ZrN pillars, and is accessible through the pores) are commensurate in scope with the Declaration.” And that: “Indeed, one of ordinary skill in the art would understand that the bactericidal metal element, being located around or within the TiN or ZrN pillars, has low accessibility from outside of the composite coating. In other words, the flow of fluid around the bactericidal metal element in the composite coating, which is required for passive release, is significantly limited by the pillars and the pores. As a result, effective controlled release of the bactericidal ions is achieved only in response to applications of electrical potential to the bactericidal layer, thereby allowing significantly better longevity to be achieved.” (p. 12 last two paragraphs through p. 13, 1st paragraph).
In response the examiner argues that co-deposition using sputtering is clearly taught by OSTRUM, for example, see paragraph ([0034]). Additionally, LINK as well as both Staubade et al. and Whitehead et al. teach co-deposition by sputtering (cosputtering) of silver and/or copper with TiN producing a nanocomposite layer.
Applicant further argues that: “Indeed, Saubade is silent regarding the composite coating as recited in the independent claims. As commented in the Declaration dated November 21, 2025, the coating of Saubade does not have "bactericidal metal element ... disposed at least partially around or within the TiN or ZrN pillars," as the silver nanoparticles of Saubade are larger than any other visible features on the surface of the TiN coatings and unlikely to fit into any opening or pores, if exist; in fact accessible pores would actually render the coatings of Saubade unsatisfactory for the intended purposes of acting as a load bearing structure […].”
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Response to Applicants §1.132 declaration filed 11/21/2025:
The examiner has fully considered Applicants declaration filed 11/21/2025 and finds the declaration not convincing because (1) the declaration does not include comparative data (side-by-side comparison with the closest prior art or closer – MPEP §716.02(e), and is considered an opinion declaration, and (2) the positions in the declaration are not considered commensurate with the rejected claims as the argument is directed at an intended use of a composition of matter. Particularly Applicant suggests that: “In summary, the composite bactericidal layer of the present application achieves antibacterial effects similar to Ostrum, but with a much longer longevity due to the feature of on-demand ion release, which allows the release of bactericidal ions only when there is a need. This is a significant and unexpected improvement over Ostrum.” (item 14), however, the claims are not limited to compositions having “a much longer longevity due to the feature of on-demand ion release, which allows the release of bactericidal ions only when there is a need”. Additionally, this as an argument based on the intended use of a composition of matter which is considered prima facie obvious as discussed above. The argument is therefore a convincing basis for allowance of the instant claims.
Conclusion
Claims 9, 13-15, 17 and 19-31 are pending and have been examined on the merits. Claims 9, 13-15, 17 and 19-31 are rejected under 35 U.S.C. 103. No claims allowed at this time.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IVAN A GREENE whose telephone number is (571)270-5868. The examiner can normally be reached M-F, 8-5 PM PST.
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/IVAN A GREENE/Examiner, Art Unit 1619
/TIGABU KASSA/Primary Examiner, Art Unit 1619
Prosecution Insights