DETAILED ACTION
This is in response to communication received on 12/15/25.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The text of those sections of AIA 35 U.S.C. code not present in this action can be found in previous office actions dated 1/26/22, 4/18/22, 12/19/22, 8/2/23, 1/18/24 and 10/16/24.
Election/Restrictions
Examiner notes that claims 25-26, which are explicitly drawn to an apparatus and withdrawn without traverse on 3/28/22 as a non-elected invention, have been amended.
Claim 25 and 26 have been amended to now read as "the method according to claim 15, further comprising providing an apparatus for immobilization of the biomolecule through the linking molecule on the sample surface of the substrate, the apparatus comprising" and then goes on to list apparatus limitations. Thus, the claims have been explicitly rewritten to claim two statutory categories--both a method and apparatus.
Examiner also notes that a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011). Introducing a 112(b)issue does not overcome a restriction on the record or address the actual issue behind the restriction--namely the burden of searching two different inventions belonging in separate classes.
Based on the actual content of the claim and the previous election without traverse, Examiner maintains the restriction.
Claim Rejections - 35 USC § 103
The claim rejection(s) under AIA 35 U.S.C. 103 as being obvious over Paulussen et al. US PG Pub 2007/0292972 hereinafter PAULUSSEN in view of Gladish et al. US PGPub 2016/0250831 hereinafter GLADISH and Gilliam et al. US PG Pub 2016/0039979 hereinafter GILLIAM on claim 15-16, 19-24, 30-35, 37-39, 42 and 46 are withdrawn because the independent claims 15 and 30 have been amended and claim 20 has been cancelled.
The claim rejection(s) under AIA 35 U.S.C. 103 as being obvious over Paulussen et al. US PGPub 2007/0292972 hereinafter PAULUSSEN in view of Gladish et al. US PG Pub 2016/0250831 hereinafter GLADISH and Gilliam et al. US PG Pub 2016/0039979 hereinafter GILLIAM as applied to claim 15 above, and further in view of Cahalan et al. US PG Pub 2012/0107901 hereinafter CAHALAN on claim 36 is withdrawn because the independent claims 15 and 30 have been amended.
The claim rejection(s) under AIA 35 U.S.C. 103 as being obvious over Paulussen et al. US PGPub 2007/0292972 hereinafter PAULUSSEN in view of Gladish et al. US PG Pub 2016/0250831 hereinafter GLADISH and Gilliam et al. US PG Pub 2016/0039979 hereinafter GILLIAM as applied to claim 15 above, and further in view of Kaplan et al. US PGpub 2007/0281117 hereinafter KAPLAN on claim 43, 44, 45, and 46 are withdrawn because the independent claims 15 and 30 have been amended.
Claim(s) 15-16, 19, 21-24, 30, 35, 38-42 and 46-54 are rejected under 35 U.S.C. 103 as being unpatentable over Paulussen et al. US PGPub 2007/0292972 hereinafter PAULUSSEN in view of Gladish et al. US PG Pub 2016/0250831 hereinafter GLADISH and Gilliam et al. US PG Pub 2016/0039979 hereinafter GILLIAM as evidenced by Sigma-Aldritch Product Specification hereinafter SIGMA-Aldrich and 4.09 Plasma Polymer Deposition and Coatings on Polymers by D. Hegemann hereinafter PLASMA.
As for claim 15, PAULUSSEN teaches "The present invention is related to method for immobilizing a biomolecule on a surface by generating and maintaining an atmospheric pressure plasma, said method comprising the steps of: introducing a sample in the space between two electrodes, a mixed atmosphere being present between said electrodes, applying an alternating voltage to said electrodes for generating and maintaining a plasma in the volumetric space between the electrodes, said voltage having a profile as a function of time, defined by a sequence of time periods during which a positive or zero voltage is applied, alternated with time periods during which a negative or zero voltage is applied, and depositing a coating on a surface of said sample, characterised in that said mixed atmosphere comprises an aerosol comprising a reactive precursor and an aerosol comprising a biomolecule, both of which are deposited and immobilised during the depositing step" (abstract), i.e. A... method for the immobilization of a biomolecule through a linking molecule on a sample surface of a substrate by generating and maintaining a non-thermal atmospheric pressure plasma ... the method comprising ... steps of ... depositing the linking molecule onto the sample surface through exposing the sample surface to a ... plasma jet and the linking molecule, generating a linking layer onto the sample surface; and ... depositing the biomolecule onto the linking layer through exposing the linking layer to a ... plasma jet and the biomolecule.
Examiner notes that PAULUSSEN teaches a single step process in which the reactive precursor, i.e. linking molecule, and the biomolecule are applied simultaneously in the same plasma, i.e. plasma jet. Thus, PAULUSSEN is silent on a first step, a first plasma jet, a second step and a second plasma jet.
However, in general, the transposition of process steps or the splitting of one step into two, where the processes are substantially identical or equivalent in terms of function, manner and result, was held to be not patentably distinguish the processes. Ex parte Rubin, 128 USPQ 440 (Bd. Pat. App. 1959). See MPEP 2144 IV. In this case, splitting the simultaneous single step process into a two-step process in which there is a first step the linking molecule is deposited onto the sample surface through exposing the sample surface to a first plasma jet and the linking molecule ... and sequentially, in a second step, depositing the biomolecule onto the linking layer through exposing the linking layer to a second plasma jet and the biomolecule because both processes are substantially identical or equivalent in terms of function, manner and result as both result in an immobilized biomolecule on the surface using a reactive linking group.
PAULUSSEN further teaches “The precursors include organic molecules (like acrylic compounds, alkanes, alkenes, etc.) and organic/inorganic hybrid molecules (like HMDSO and TEOS)” (paragraph 44, lines 43-46).
As evidenced by PLASMA (Page 209, section 4.09.1.2.1, lines 1-3) and SIGMA-ALDRITCH (See page 1) both HMDSO and TEOS have multiple moieties. HMDSO (hexamethyldisiloxane) has three alkyl moieties attached to the Si-O-Si on either side and TEOS (tetraethyl orthosilicate) has four alkane groups attached to the SiO4 group in the center. Therefore, PAULUSSEN teaches wherein the linking molecule is a molecule comprising two or more moieties.
PAULUSSEN is silent on wherein the first plasma jet is generated at a first electrode power and the second plasma jet is generated at a second electrode power, wherein the first electrode power is at least 1.5 W/cm2 and the second electrode power is at most 1.0 W/cm2, such that the first electrode power is higher than the second electrode power.
GLADISH teaches "the inventive subject matter contemplates: providing a substrate; providing a biomaterial to be affixed to the substrate; and subjecting the substrate and biomaterial to reactive species from a plasma generated by an atmospheric plasma apparatus until the biomaterial affixes to the substrate" (abstract, lines 1-5).
GLADISH further teaches "Pulsed or unpulsed, high-power plasmas may be used to produce durable coatings that may be applied using a plasma exposure of a second or less (as opposed to minutes), and that a continuously applied, effective power density for generating thicker, more durable coatings, may be between 1 and 5 W/cm2" (paragraph 82, lines 1-6), i.e. wherein power of the plasma is a variable that effects the thickness and durability of the resulting coating and teaches a power that overlaps with both ranges mentioned by the claims.
It would have been within the skill of the ordinary artisan at the time of effective filing to design the power of each plasma jet in each separate step such that a desired thickness and durability of the coating produced in each step is achieved. Discovery of optimum value of result effective variable in known process is ordinarily within the skill of the art. In re Boesch, CCPA 1980, 617 F.2d 272, 205 USPQ215.
PAULUSSEN further teaches "The most important feature of atmospheric pressure plasmas in this context is however the absence of highly energetic species in the plasma. While complex precursor molecules get fractured when exposed to vacuum plasma, they retain their structure to a high extent in atmospheric pressure plasmas. The latter phenomenon is attributed to the reduced mean free path length of the active species due to the presence of high amounts of gas molecules. Accordingly this new technology also allows the incorporation of biomolecules into coatings with only minor modifications" (paragraph 44, lines 6-15), i.e. wherein the second plasma jet is generated at the second electrode power such that a functionality of the biomolecule is retained.
PAULUSSEN and GLADISH are silent on the biomolecule being an antibody or the biomolecule having anti-bacterial properties and/or anti-fungal properties.
PAULUSSEN teaches "The method of immobilisation according to the present invention comprises the incorporation of biomolecules, and proteins in particular, in thin plasma polymerized coatings" (paragraph 43, lines 1-4).
GILLIAM teaches "In another aspect, a chemical or biological component is injected into the stream of treated particles downstream of the treatment zone to react with the new reactive sites or radicals on the surf ace of the particles for grafting or immobilization. The chemical can be added as a gas, vapor, liquid, mist, spray, or any similar method. The list of chemicals for grafting is numerous and can be any from those that are organic molecules, hybrid molecules, biological extracts or materials, biomolecules, and bioactive molecules. Suitable chemicals for grafting can include ... biomolecules ... antibodies, proteins, or others" (paragraph 44) and "Once the particles enter the treatment chamber, they encounter the plasma discharge that contains high energy plasma species, including ions, electrons, excited neutrals, and radicals" (paragraph 37, lines 1-4).
It would have been obvious to one of ordinary skill in the art before the effective filing date to apply antibodies with the process of PAULUSSEN and GLADISH such that the biomolecule being an antibody ... wherein the second plasma jet is generated at the second electrode power such that a functionality of the antibody ... is retained because GILLIAM teaches that antibodies were known biomolecules used in plasma treatments alongside proteins. It is a prima facie case of obviousness to substitute one known element for another to obtain predictable results.
As for claim 16, PAULUSSEN teaches "introducing a sample in the space between two electrodes, a mixed atmosphere being present between said electrodes, applying an alternating voltage to said electrodes for generating and maintaining a plasma in the volumetric space between the electrodes" (abstract, lines 4-8) and "The mixed atmosphere can comprise ... argon" (paragraph 16, line 1 ), i.e. wherein the plasma jet can be generated using a plasma gas, which is chosen from the group comprising ... argon.
As noted above, PAULUSSEN is silent on a second plasma jet, and explicitly only teaches a simultaneous step. However, as argued above, in general, the transposition of process steps or the splitting of one step into two, where the processes are substantially identical or equivalent in terms of function, manner and result, was held to be not patentably distinguish the processes. Ex parte Rubin, 128 USPQ 440 (Bd. Pat. App. 1959). See MPEP 2144 IV. As such, it would have been obvious to split the steps into a first and second step such that there is a second plasma jet being produced in the mixed atmosphere comprising argon such that argon is used as plasma gas to generate the second plasma jet.
As for claim 19, PAULUSSEN teaches "The sample can comprise metal, ceramic or plastic materials" (paragraph 17, line 1-2), i.e. wherein the substrate is chosen from the group comprising ... metals, plastics ... ceramics.
As for claim 21, PAULUSSEN teaches “The precursors include organic molecules (like acrylic compounds, alkanes, alkenes, etc.) and organic/inorganic hybrid molecules (like HMDSO and TEOS)” (paragraph 44, lines 43-46).
As evidenced by SIGMA-ALDRITCH (See page 1), TEOS (tetraethyl orthosilicate) has four alkane groups attached to the SiO4 group in the center. Therefore, PAULUSSEN teaches wherein at least one of the two more moieties of the linking molecule is chosen from the group comprising… alkane.
As for claim 22, PAULUSSEN teaches "During this process, proteins will not be forced to change their conformation in order to bind to a surface because the coating, preferably a coating with a high-water content, will be formed around the proteins, thus stabilising and protecting them. It remains however important that the orientation of the proteins near the surf ace allows them to expose their biologically active sites" (paragraph 44, lines 31-37), i.e. wherein said biomolecule is a biologically... active molecule.
As for claim 24, PAULUSSEN is silent on a second plasma jet, and explicitly only teaches a simultaneous step. However, as argued above, in general, the transposition of process steps or the splitting of one step into two, where the processes are substantially identical or equivalent in terms of function, manner and result, was held to be not patentably distinguish the processes. Ex parte Rubin, 128 USPQ 440 (Bd. Pat. App.1959). SeeMPEP2144 IV.
Considering the above, further consider that PAULUSSEN teaches "an aerosol comprising the biomolecule" (paragraph 19, lines 2-3) wherein the aerosol comprising the biomolecule is apart of the mixed atmosphere where the plasma is being generated, i.e. wherein said biomolecule is administrated to the second plasma jet in an aqueous aerosol.
As for claim 30, PAULUSSEN teaches "The present invention is related to method for immobilizing a biomolecule on a surface by generating and maintaining an atmospheric pressure plasm a, said method com prising the steps of: introducing a sample in the space between two electrodes, a mixed atmosphere being present between said electrodes, applying an alternating voltage to said electrodes for generating and maintaining a plasma in the volumetric space between the electrodes, said voltage having a profile as a function of time, defined by a sequence of time periods during which a positive or zero voltage is applied, alternated with time periods during which a negative or zero voltage is applied, and depositing a coating on a surface of said sample, characterised in that said mixed atmosphere comprises an aerosol comprising a reactive precursor and an aerosol comprising a biomolecule, both of which are deposited and immobilised during the depositing step" (abstract), i.e. A... method for the immobilization of a biomolecule through a linking molecule on a sample surface of a substrate ... the method comprising ... steps of ... the linking molecule is deposited onto the sample surface through exposing the sample surface to a ... plasma jet and the linking molecule, generating a linking layer onto the sample surface; and ... the biomolecule is deposited onto the linking layer through exposing the linking layer to a ... plasma jet and the biomolecule.
Examiner notes that PAULUSSEN teaches a single step process in which the reactive precursor, i.e. linking molecule, and the biomolecule are applied simultaneously in the same plasma, i.e. plasma jet. Thus, PAULUSSEN is silent on a first step, a first plasma jet, a second step and a second plasma jet.
However, in general, the transposition of process steps or the splitting of one step into two, where the processes are substantially identical or equivalent in terms of function, manner and result, was held to be not patentably distinguish the processes. Ex parte Rubin, 128 USPQ 440 (Bd. Pat. App. 1959). See MPEP 2144 IV. In this case, splitting the simultaneous single step process into a two-step process in which there is a first step the linking molecule is deposited onto the sample surface through exposing the sample surface to a first plasma jet and the linking molecule ... and sequentially, in a second step the biomolecule is deposited onto the linking layer through exposing the linking layer to a second plasma jet and the biomolecule because both processes are substantially identical or equivalent in terms of function, manner and result as both result in an immobilized biomolecule on the surface using a reactive linking group.
PAULUSSEN further teaches “The precursors include organic molecules (like acrylic compounds, alkanes, alkenes, etc.) and organic/inorganic hybrid molecules (like HMDSO and TEOS)” (paragraph 44, lines 43-46).
As evidenced by PLASMA (Page 209, section 4.09.1.2.1, lines 1-3) and SIGMA-ALDRITCH (See page 1) both HMDSO and TEOS have multiple moieties. HMDSO (hexamethyldisiloxane) has three alkyl moieties attached to the Si-O-Si on either side and TEOS (tetraethyl orthosilicate) has four alkane groups attached to the SiO4 group in the center. Therefore, PAULUSSEN teaches wherein the linking molecule is a molecule comprising two or more moieties.
PAULUSSEN is silent on wherein the first plasma jet is generated at a first electrode power and the second plasma jet is generated at a second electrode power, wherein the first electrode power is at least 1.5 W/cm2 and the second electrode power is at most 1.0 W/cm2, such that the first electrode power is higher than the second electrode power.
GLADISH teaches "the inventive subject matter contemplates: providing a substrate; providing a biomaterial to be affixed to the substrate; and subjecting the substrate and biomaterial to reactive species from a plasma generated by an atmospheric plasma apparatus until the biomaterial affixes to the substrate" (abstract, lines 1-5).
GLADISH further teaches "Pulsed or unpulsed, high-power plasmas may be used to produce durable coatings that may be applied using a plasma exposure of a second or less (as opposed to minutes), and that a continuously applied, effective power density for generating thicker, more durable coatings, may be between 1 and 5 W/cm2" (paragraph 82, lines 1-6), i.e. wherein power of the plasma is a variable that effects the thickness and durability of the resulting coating and teaches a power that overlaps with both ranges mentioned by the claims.
It would have been within the skill of the ordinary artisan at the time of effective filing to design the power of each plasma jet in each separate step such that a desired thickness and durability of the coating produced in each step is achieved. Discovery of optimum value of result effective variable in known process is ordinarily within the skill of the art. In re Boesch, CCPA 1980, 617 F.2d 272, 205 USPQ215.
PAULUSSEN and GLADISH are silent on the biomolecule being an antibody or the biomolecule having anti-bacterial properties and/or anti-fungal properties.
PAULUSSEN teaches "The method of immobilisation according to the present invention comprises the incorporation of biomolecules, and proteins in particular, in thin plasma polymerized coatings" (paragraph 43, lines 1-4).
GILLIAM teaches "In another aspect, a chemical or biological component is injected into the stream of treated particles downstream of the treatment zone to react with the new reactive sites or radicals on the surf ace of the particles for grafting or immobilization. The chemical can be added as a gas, vapor, liquid, mist, spray, or any similar method. The list of chemicals for grafting is numerous and can be any from those that are organic molecules, hybrid molecules, biological extracts or materials, biomolecules, and bioactive molecules. Suitable chemicals for grafting can include ... biomolecules ... antibodies, proteins, or others" (paragraph 44) and "Once the particles enter the treatment chamber, they encounter the plasma discharge that contains high energy plasma species, including ions, electrons, excited neutrals, and radicals" (paragraph 37, lines 1-4).
It would have been obvious to one of ordinary skill in the art before the effective filing date to apply antibodies with the process of PAULUSSEN and GLADISH such that the biomolecule being an antibody... wherein the second plasma jet is generated at the second electrode power such that a functionality of the antibody ... is retained because GILLIAM teaches that antibodies were known biomolecules used in plasma treatments alongside proteins. It is a prima facie case of obviousness to substitute one known element for another to obtain predictable results.
As for claim 35, PAULUSSEN and GLADISH are silent on the biomolecule being an antibody.
PAULUSSEN teaches "The method of immobilisation according to the present invention comprises the incorporation of biomolecules, and proteins in particular, in thin plasma polymerized coatings" (paragraph 43, lines 1-4).
GILLIAM teaches "In another aspect, a chemical or biological component is injected into the stream of treated particles downstream of the treatment zone to react with the new reactive sites or radicals on the surface of the particles for grafting or immobilization. The chemical can be added as a gas, vapor, liquid, mist, spray, or any similar method. The list of chemicals for grafting is numerous and can be any from those that are organic molecules, hybrid molecules, biological extracts or materials, biomolecules, and bioactive molecules. Suitable chemicals for grafting can include ... biomolecules ... antibodies, proteins, or others" (paragraph 44) and "Once the particles enter the treatment chamber, they encounter the plasma discharge that contains high energy plasma species, including ions, electrons, excited neutrals, and radicals" (paragraph 37, lines 1-4).
It would have been obvious to one of ordinary skill in the art before the effective filing date to apply antibodies with the process of PAULUSSEN and GLADISH such that the biomolecule being an antibody... wherein the second plasma jet is generated at the second electrode power such that a functionality of the antibody ... is retained because GILLIAM teaches that antibodies were known biomolecules used in plasma treatments alongside proteins. It is a prima facie case of obviousness to substitute one known element for another to obtain predictable results.
As for claim 37, PAULUSSEN is silent on the first and second electrode power.
GLADISH teaches "the inventive subject matter contemplates: providing a substrate; providing a biomaterial to be affixed to the substrate; and subjecting the substrate and biomaterial to reactive species from a plasma generated by an atmospheric plasma apparatus until the biomaterial affixes to the substrate" (abstract, lines 1-5).
GLADISH further teaches "Pulsed or unpulsed, high-power plasmas may be used to produce durable coatings that may be applied using a plasma exposure of a second or less (as opposed to minutes), and that a continuously applied, effective power density for generating thicker, more durable coatings, may be between 1 and 5 W/cm2" (paragraph 82, lines 1-6), i.e. wherein power of the plasma is a variable that effects the thickness and durability of the resulting coating and teaches a power that is within the same magnitude by the claims.
It would have been within the skill of the ordinary artisan at the time of effective filing to design the power of each plasma jet in each separate step such that a desired thickness and durability of the coating produced in each step is achieved. Discovery of optimum value of result effective variable in known process is ordinarily within the skill of the art. In re Boesch, CCPA 1980, 617 F.2d 272, 205 USPQ215.
As for claim 38, PAULUSSEN teaches "The coating is deposited on the surface of both electrodes and on the glass and silicon substrates attached to the electrodes" (paragraph 49, lines 7-9), i.e. wherein the sample surface of the substrate is glass or quartz.
As for claim 39, PAULUSSEN teaches "The coating is deposited on the surface of both electrodes and on the glass and silicon substrates attached to the electrodes" (paragraph 49, lines 7-9), i.e. wherein the sample surface of the substrate includes silicon or silicon wafer.
As for claim 40, PAULUSSEN teaches “This technology can pave the way to a whole new realm of future applications in the medical, chemical, environmental, food, materials and many other industrial sectors, including but not limited to… Templates for extra-corporeal and/or in-vivo growth of functional tissues” (paragraph 28, line 10 – paragraph 37) and “Furthermore, any substrate, of any form or material, can be coated with biomolecules using the method of the present invention” (paragraph 41, lines 15-17), i.e. wherein the sample surface of the substrate includes skin or tissue.
As for claim 41, PAULUSSEN teaches “This technology can pave the way to a whole new realm of future applications in the medical, chemical, environmental, food, materials and many other industrial sectors, including but not limited to… Templates for extra-corporeal and/or in-vivo growth of functional tissues” (paragraph 28, line 10 – paragraph 37) and “Furthermore, any substrate, of any form or material, can be coated with biomolecules using the method of the present invention” (paragraph 41, lines 15-17), i.e. wherein the samplesurface of the substrate includes biological materials.
As for claim 42, Examiner notes that Applicant is essentially trying to limit the claim to a hypothetical with very little perimeters defining it. For example, for what period of time is the antibody hypothetical process that is not actually performed in the process? How much damage would be considered denatured or destroying function? For this reason, that the hypothetical is so broad can encompass any process, it is position of the Examiner that this is not limiting or capable of distinguishing over the prior art. Any power of plasma exposure would cause denaturing and destruction is it is undergone for long enough, e.g. three days. Furthermore, any number of impurities within the plasma exposure could also 'destroy' a certain amount of functionality.
PAULUSSEN specifically teaches “The most important feature of atmospheric pressure plasmas in this context is however the absence of highly energetic species in the plasma. While complex precursor molecules get fractured when exposed to vacuum plasma, they retain their structure to a high extent in atmospheric pressure plasmas. The latter phenomenon is attributed to the reduced mean free path length of the active species due to the presence of high amounts of gas molecules. Accordingly this new technology also allows the incorporation of biomolecules into coatings with only minor modifications” (paragraph 44, lines 6-16), and as combined with GLADISH and GILLIAM above i.e. wherein the plasma of the first electrode power would denature or destroy the functionality of the antibody or the biomolecule having anti-bacterial properties and/or anti-fungal properties.
As for claim 46, PAULUSSEN teaches "The incorporation of biomolecules may be accomplished physically (by embedding) or by covalent linking, depending on the reaction conditions and the type of precursor used" (paragraph 44, lines 27-30). Furthermore, Examiner notes that non-permenent and releasable are very broad. Namely, the actual process of releasing the biomolecule is not required, so therefore it merely requires the capability. Considering the PAULUSSEN teaches embodiments wherein the biomolecule is merely embedded in the polymer and is not chemically attached, it is the position of the Examiner that the biomolecule is non-permanently deposited onto the linking layer such that the biomolecule such that the biomolecule is releasable from the linking layer is inherent as it is not attached through a chemical bond.
As for claim 47, PAULUSSEN teaches “The incorporation of biomolecules may be accomplished physically (by embedding) or by covalent linking, depending on the reaction conditions and the type of precursor used” (paragraph 44, lines 28-30) and “Precursors that contain functional groups like amines and carboxyls will chemically bind to biomolecules while this is less likely to occur with precursors like alkanes” (paragraph 44, lines 39-42), i.e. wherein at least one of the two or more moieties of the linking molecule is suitable for the attachment of the linking layer to the biomolecule, wherein ‘suitable’ is interpreted to mean any linking molecule capable of that function, even in small amounts.
As for claim 48, PAULUSSEN is silent on wherein at least one of the two or more moieties of the linking molecule is suitable for the attachment of the linking layer to the sample surface.
GILLIAM teaches “These reactions can involve ablation of surface elements or molecule side groups, bond cleavage, etching, surface cross- linking, and the creation of reactive functional groups. The type of reactions and reactivity of the particle surfaces depend on the particle material, the plasma process gas or mixture, and the plasma process conditions. The process can be operated with addition of a chemical precursor, which reacts with the plasma species to form derivatives that react with the particle surfaces, resulting in the formation of new chemical functional groups. The chemical precursor can be chosen based on the desired functionality of the surface of the treated particles from a wide variety of chemicals that can be delivered in gas, vapor, or liquid form” (paragraph 15, lines 7-19), i.e. wherein at least one of the… moieties of the linking molecule is suitable for the attachment of the linking layer to the sample surface.
It would have been obvious to one of ordinary skill in the art before the effective filing date to include the surface reacting functionalities of GILLIAM in the process of PAULUSSEN such that wherein at least one of the two or more moieties of the linking molecule is suitable for the attachment of the linking layer to the sample surface because GILLIAM teaches that such linking allows for the attachment of desired functional groups to a substrate surface for later treatment.
As for claim 49, PAULUSSEN teaches “The incorporation of biomolecules may be accomplished physically (by embedding) or by covalent linking, depending on the reaction conditions and the type of precursor used” (paragraph 44, lines 28-30) and “Precursors that contain functional groups like amines and carboxyls will chemically bind to biomolecules while this is less likely to occur with precursors like alkanes” (paragraph 44, lines 39-42), i.e. wherein a first moiety of the two or more moieties of the linking molecule is suitable for the attachment of the linking layer to the biomolecule, wherein ‘suitable’ is interpreted to mean any linking molecule capable of that function, even in small amounts.
PAULUSSEN is silent on wherein a second moiety of the two or more moieties of the linking molecule is suitable for the attachment of the linking layer to the sample surface.
GILLIAM teaches “These reactions can involve ablation of surface elements or molecule side groups, bond cleavage, etching, surface cross- linking, and the creation of reactive functional groups. The type of reactions and reactivity of the particle surfaces depend on the particle material, the plasma process gas or mixture, and the plasma process conditions. The process can be operated with addition of a chemical precursor, which reacts with the plasma species to form derivatives that react with the particle surfaces, resulting in the formation of new chemical functional groups. The chemical precursor can be chosen based on the desired functionality of the surface of the treated particles from a wide variety of chemicals that can be delivered in gas, vapor, or liquid form” (paragraph 15, lines 7-19), i.e. wherein… moieties of the linking molecule is suitable for the attachment of the linking layer to the sample surface.
It would have been obvious to one of ordinary skill in the art before the effective filing date to include the surface reacting functionalities of GILLIAM in the process of PAULUSSEN such that wherein a second moiety of the two or more moieties of the linking molecule is suitable for the attachment of the linking layer to the sample surface because GILLIAM teaches that such linking allows for the attachment of desired functional groups to a substrate surface for later treatment.
As for claim 50, PAULUSSEN teaches “The incorporation of biomolecules may be accomplished physically (by embedding) or by covalent linking, depending on the reaction conditions and the type of precursor used” (paragraph 44, lines 28-30) and “The method of immobilisation according to the present invention comprises the incorporation of biomolecules, and proteins in particular, in thin plasma polymerized coatings” (paragraph 43, lines 1-4), i.e. wherein at least one of the two or more moieties of the linking molecule is suitable for polymerization of the linking molecule.
As for claim 51, PAULUSSEN further teaches “The precursors include organic molecules (like acrylic compounds, alkanes, alkenes, etc.) and organic/inorganic hybrid molecules (like HMDSO and TEOS)” (paragraph 44, lines 43-46).
As evidenced by SIGMA-ALDRITCH (See page 1), TEOS (tetraethyl orthosilicate) has four alkane groups attached to the SiO4 group in the center. Therefore, PAULUSSEN teaches wherein the two or more moieties of the linking molecule include a first moiety and a second moiety, wherein the first moiety and the second moiety are not located alongside each other as the first and second moiety are opposite each other on the molecule.
As for claim 52, PAULUSSEN teaches “It remains however important that the orientation of the proteins near the surface allows them to expose their biologically active sites or that the cross-link density of the plasma polymer is sufficiently low to allow diffusion of the matching substrates to completely embedded proteins” (paragraph 44, lines 35-39), i.e. wherein the steps of the depositing the linking molecule onto the sample surface and the depositing the biomolecule onto the linking layer include controlling an orientation of the immobilization of the biomolecule.
As for claim 53, PAULUSSEN is silent on wherein the step of the depositing the linking molecule onto the sample surface includes homogenizing the first plasma jet and/or the step of the depositing the biomolecule onto the linking layer includes homogenizing the second plasma jet.
GILLIAM teaches “This method involves a non-thermal atmospheric plasma source 1 generated using any known source that creates a homogeneous, current-carrying arc in which the nozzle is the anode and the plasma exits the source at zero potential and high density of plasma species” (paragraph 30, lines 5-10) and “A method and apparatus described in this disclosure bring about fast, uniform surface treatment in a configuration conducive for scale-up” (paragraph 29, lines 1-3), i.e. wherein when applying a plasma coating homogenizing the… plasma jet.
It would have been obvious to one of ordinary skill in the art before the effective filing date to include wherein the step of the depositing the linking molecule onto the sample surface includes homogenizing the first plasma jet and/or the step of the depositing the biomolecule onto the linking layer includes homogenizing the second plasma jet in the combined process of PAULUSSEN, GLADISH and GILLIAM because GILLIAM teaches that such a homogeneous plasma produces a uniform coating.
As for claim 54, PAULUSSEN is silent on wherein said homogenizing the first plasma jet and/or said homogenizing the second plasma jet includes using flow disturbance means for the first plasma jet and/or the second plasma jet.
GILLIAM teaches “This method involves a non-thermal atmospheric plasma source 1 generated using any known source that creates a homogeneous, current-carrying arc in which the nozzle is the anode and the plasma exits the source at zero potential and high density of plasma species” (paragraph 30, lines 5-10) and “A method and apparatus described in this disclosure bring about fast, uniform surface treatment in a configuration conducive for scale-up” (paragraph 29, lines 1-3), i.e. wherein the nozzle is a flow disturbance means for the plasma jet.
It would have been obvious to one of ordinary skill in the art before the effective filing date to include wherein said homogenizing the first plasma jet and/or said homogenizing the second plasma jet includes using flow disturbance means for the first plasma jet and/or the second plasma jet in the combined process of PAULUSSEN, GLADISH and GILLIAM because GILLIAM teaches that such a homogeneous plasma produces a uniform coating.
Claim(s) 31-34 are rejected under 35 U.S.C. 103 as being unpatentable over Paulussen et al. US PGPub 2007/0292972 hereinafter PAULUSSEN in view of Gladish et al. US PG Pub 2016/0250831 hereinafter GLADISH and Gilliam et al. US PG Pub 2016/0039979 hereinafter GILLIAM as evidenced by Sigma-Aldritch Product Specification hereinafter SIGMA-Aldrich and 4.09 Plasma Polymer Deposition and Coatings on Polymers by D. Hegemann hereinafter PLASMA as applied to claim 15 above, and further as evidenced by The Engineering ToolBox Pressure hereinafter PRESSURE, page 2, Standard Atmospheric Pressure).
As for claim 31, PAULUSSEN teaches that the conditions of its plasma are "low temperature (room temperature up to 60° C.) and ambient pressure" (paragraph 45, lines 1-5), wherein ambient pressure is understood to be atmospheric pressure which is equal to 1.01 bar (see The Engineering ToolBox Pressure hereinafter PRESSURE, page 2, Standard Atmospheric Pressure), i.e. wherein the first step and the second step are performed while generating and maintaining a non-thermal atmospheric pressure plasma at a pressure between 0.6 and 5.0 bar.
As for claim 32, PAULUSSEN teaches that the conditions of its plasma are "low temperature (room temperature up to 60° C.) and ambient pressure" (paragraph 45, lines 1-5), wherein ambient pressure is understood to be atmospheric pressure which is equal to 1.01 bar (see The Engineering ToolBox Pressure hereinafter PRESSURE, page 2, Standard Atmospheric Pressure), i.e. wherein the first and second step are performed while generating and maintaining a non-thermal atmospheric pressure plasma at a pressure between 0. 6 and 5. 0 bar and a temperature that overlaps with the range of between 5°C and 60°C. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d, 1362, 1365-66 (Fed. Cir. 1997). See M PEP 2144.05.
As for claim 33, PAULUSSEN teaches that the conditions of its plasma are "low temperature (room temperature up to 60° C.) and ambient pressure" (paragraph 45, lines 1-5), wherein ambient pressure is understood to be atmospheric pressure which is equal to 1.01 bar (see The Engineering ToolBox Pressure hereinafter PRESSURE, page 2, Standard Atmospheric Pressure), i.e. wherein the first step or the second step are performed while generating and maintaining a non-thermal atmospheric pressure plasma at a pressure between 0.6 and 5.0 bar and a temperature that overlaps with the range of between 5°C and 60°C. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d, 1362, 1365-66 (Fed. Cir. 1997). See MPEP 2144.05.
As for claim 34, PAULUSSEN teaches that the conditions of its plasma are "low temperature (room temperature up to 60° C.) and ambient pressure" (paragraph 45, lines 1-5), and, in view of the rejection of claim 31 from which 34 depends, i.e. wherein the first or the second step are performed while generating and maintaining a plasma at a temperature that overlaps with the range of between 5°C and 60°C. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d, 1362, 1365-66 (Fed. Cir.1997). See MPEP 2144.05.
Claim(s) 36 is rejected under 35 U.S.C. 103 as being unpatentable over Paulussen et al. US PGPub 2007/0292972 hereinafter PAULUSSEN in view of Gladish et al. US PG Pub 2016/0250831 hereinafter GLADISH and Gilliam et al. US PG Pub 2016/0039979 hereinafter GILLIAM as evidenced by Sigma-Aldritch Product Specification hereinafter SIGMA-Aldrich and 4.09 Plasma Polymer Deposition and Coatings on Polymers by D. Hegemann hereinafter PLASMA as applied to claim 15 above, and further in view of Cahalan et al. US PG Pub 2012/0107901 hereinafter CAHALAN.
As for claim 36, PAULUSSEN, GLADISH and GILLIAM are silent on wherein the biomolecule has antibacterial properties and/or anti-fungal properties, wherein the second plasma jet is generated at the second electrode power such that the functionality biomolecule having anti-bacterial properties and/or anti-fungal properties is retained.
PAULUSSEN does teach "The method of immobilisation according to the present invention comprises the incorporation of biomolecules, and proteins in particular, in thin plasma polymerized coatings" (paragraph 43, lines 1-4).
CALAHAN teaches "A method of treating the surf ace of a medical device with a biomolecule comprising the steps of: ... attaching a biomolecule, such as heparin, to the polyolefin substrate following formation of the plasma-deposited polyacrylic acid coating on the polyolefin substrate" (abstract).
CALAHAN teaches "In step d) of the process of the Present invention, the aminofunctional polysiloxane surface is contacted with a biomolecule under conditions effective to attach the biomolecule to the substrate. Examples of biomolecules that may be attached to the surface include antibacterial agents, antimicrobial agents ... antibodies ... protein" (Paragraph 53, lines 1-9).
It would have been obvious to one of ordinary skill in the art before the effective filing date to apply antibodies with the process of PAULUSSEN and GLADISH such that wherein the biomolecule has antibacterial properties and/or anti-fungal properties, wherein the second plasma jet is generated at the second electrode power such that the functionality biomolecule having anti-bacterial properties and/or anti-fungal properties is retained because CALAHAN teaches that antibodies were known biomolecules used in plasma treatments alongside proteins. It is a prima facie case of obviousness to substitute one known element for another to obtain predictable results.
Claim(s) 43-46 rejected under 35 U.S.C. 103 as being unpatentable over Paulussen et al. US PGPub 2007/0292972 hereinafter PAULUSSEN in view of Gladish et al. US PG Pub 2016/0250831 hereinafter GLADISH and Gilliam et al. US PG Pub 2016/0039979 hereinafter GILLIAM as evidenced by Sigma-Aldritch Product Specification hereinafter SIGMA-Aldrich and 4.09 Plasma Polymer Deposition and Coatings on Polymers by D. Hegemann hereinafter PLASMA as applied to claim 15 above, and further in view of Kaplan et al. US PGpub 2007/0281117 hereinafter KAPLAN.
As for claim 43, PAULUSSEN is silent on wherein in the first step comprises creating multiple layers which serve as a linking layer.
KAPLAN teaches "In another aspect of the present invention, a method for manufacturing an intraluminal device bearing a therapeutic agent releasable from the device in a time-controlled manner comprises exposing a metallic substrate to a gaseous plasma form of a substance that polymerizes in the plasma form under conditions causing the substance to form a polymer anchor coating on the substrate. A layer containing the therapeutic agent is then deposited over the anchor coating" (paragraph 14, lines 1-9) and "The therapeutic agent may be deposited on to the polymer anchor coating by a number of methods such as dipping, spraying, brush coating, syringe deposition, chemical vapor deposition or plasma deposition" (paragraph 20, lines 1-4).
KAPLAN further teaches "In some cases, the tie layer may be a single molecule in thickness, while in other cases the layer may be several molecules in thickness, depending on the type and degree of polymerization. In one aspect of the invention, the tie layer formed by the plasma-deposited polymer on the stent surface is about 500 A or less in thickness" (paragraph 10, lines 19-24), wherein a step of forming a polymer layer to anchor another biological layer includes multiple layers of molecules, i.e. comprises creating multiple layers which serve as a linking layer.
KAPLAN teaches "It is therefore desirable to provide stents with a therapeutic agent wherein the stent may be used to deliver the therapeutic agent to a treatment site over a controlled period of time. It is further desired that once the drug has eluted into the treatment site that only the bare metal stent surface remains, or an ultra thin layer of material that does not produce any adverse biocompatibility issues at the treatment site. It is also desirable to provide methods for coupling the therapeutic agent with the stent so that the therapeutic agent remains coupled to the stent during delivery and expansion of the stent" (paragraph 9).
It would have been obvious to one of ordinary skill in the art before the effective filing date to use the polymer process of KAPLAN to form the linking layer of PAULUSSEN such that it include wherein in the first step comprises creating multiple layers which serve as a linking layer because KAPLAN teaches that such a polymer coating allows for the creation of a layer that releases a therapeutic agent over a controller period of time.
As for claim 44, PAULUSSEN is silent on wherein creating multiple layers which serve as a linking layer includes providing a first linker that improves adhesion of a second linker to the sample surface, the second linker linking the biomolecule to the first linker.
KAPLAN teaches "In another aspect of the present invention, a method for manufacturing an intraluminal device bearing a therapeutic agent releasable from the device in a time-controlled manner comprises exposing a metallic substrate to a gaseous plasma form of a substance that polymerizes in the plasma form under conditions causing the substance to form a polymer anchor coating on the substrate. A layer containing the therapeutic agent is then deposited over the anchor coating" (paragraph 14, lines 1-9) and "The therapeutic agent may be deposited on to the polymer anchor coating by a number of methods such as dipping, spraying, brush coating, syringe deposition, chemical vapor deposition or plasma deposition" (paragraph 20, lines 1-4).
KAPLAN further teaches "In some cases, the tie layer may be a single molecule in thickness, while in other cases the layer may be several molecules in thickness, depending on the type and degree of polymerization. In one aspect of the invention, the tie layer formed by the plasma-deposited polymer on the stent surface is about 500 A or less in thickness" (paragraph 10, lines 19-24), wherein a step of forming a polymer layer to anchor another biological layer includes multiple layers of molecules, i.e. comprises creating multiple layers which serve as a linking layer, wherein the first molecular layer improves adhesion of a second linker to the sample surface and the second molecular layer links the biomolecule to the first linker.
KAPLAN teaches "It is therefore desirable to provide stents with a therapeutic agent wherein the stent may be used to deliver the therapeutic agent to a treatment site over a controlled period of time. It is further desired that once the drug has eluted into the treatment site that only the bare metal stent surface remains, or an ultra thin layer of material that does not produce any adverse biocompatibility issues at the treatment site. It is also desirable to provide methods for coupling the therapeutic agent with the stent so that the therapeutic agent remains coupled to the stent during delivery and expansion of the stent" (paragraph 9).
It would have been obvious to one of ordinary skill in the art before the effective filing date to use the polymer process of KAPLAN to form the linking layer of PAULUSSEN such that it include wherein creating multiple layers which serve as a linking layer includes providing a first linker that improves adhesion of a second linker to the sample surface, the second linker linking the biomolecule to the first linker because KAPLAN teaches that such a polymer coating allows for the creation of a layer that releases a therapeutic agent over a controller period of time.
As for claim 45, PAULUSSEN is silent on in a second step multiple biomolecules are deposited onto the linking layer, including a first biomolecule and a second biomolecule, the first biomolecule being different than the second biomolecule.
KAPLAN teaches "In another aspect of the present invention, a method for manufacturing an intraluminal device bearing a therapeutic agent releasable from the device in a time-controlled manner comprises exposing a metallic substrate to a gaseous plasma form of a substance that polymerizes in the plasma form under conditions causing the substance to form a polymer anchor coating on the substrate. A layer containing the therapeutic agent is then deposited over the anchor coating" (paragraph 14, lines 1-9) and "The therapeutic agent may be deposited on to the polymer anchor coating by a number of methods such as dipping, spraying, brush coating, syringe deposition, chemical vapor deposition or plasma deposition" (paragraph 20, lines 1-4).
KAPLAN teaches "In some embodiments, the porosity of the polymer anchor coating may be varied in order to control blending of the polymer matrix with the polymer anchor coating thereby controlling release rate of the therapeutic agent from the polymer matrix. The polymeric matrix may comprise a first polymer layer disposed over the therapeutic agent with an optional second therapeutic agent disposed over the first polymer layer'' (paragraph 22, lines 4-11 ), i.e. a second step multiple biomolecules are deposited onto the linking layer, including a first biomolecule and a second biomolecule, the first biomolecule being different than the second biomolecule.
KAPLAN teaches "It is therefore desirable to provide stents with a therapeutic agent wherein the stent may be used to deliver the therapeutic agent to a treatment site over a controlled period of time. It is further desired that once the drug has eluted into the treatment site that only the bare metal stent surface remains, or an ultra thin layer of material that does not produce any adverse biocompatibility issues at the treatment site. It is also desirable to provide methods for coupling the therapeutic agent with the stent so that the therapeutic agent remains coupled to the stent during delivery and expansion of the stent" (paragraph 9).
It would have been obvious to one of ordinary skill in the art before the effective filing date to use the polymer process and biomolecule process of KAPLAN to form the linking layer of PAULUSSEN such that it include a second step multiple biomolecules are deposited onto the linking layer, including a first biomolecule and a second biomolecule, the first biomolecule being different than the second biomolecule because KAPLAN teaches that such a polymer coating allows for the creation of a layer that releases a therapeutic agent over a controller period of time.
Response to Arguments
Applicant's arguments filed 12/15/25 have been fully considered but they are not persuasive.
Applicant’s arguments are summarized and addressed below:
(a) Applicant notes that in the Final Office Action dated 1/18/24 cited PAULUSSEN’s recitation of acetylene as the linking molecule, and amended the independent claims 15 and 30 to include the limitation ‘wherein the linking molecule is a molecule comprising two or more moieties’. Acetylene only has 1 moiety so fails to meet this limitation. Applicant asserts that because of this PAULUSSEN, GLADISH and GILLIAM fail to meet this limitation.
Examiner notes that Applicant’s arguments ignore the other teachings of PAULUSSEN, specifically its teachings on HDMSO and TEOS as precursors/linking molecules. These molecules do have multiple moieties, as shown in the rejection of claim 15 and 30. As such Applicant’s arguments cannot be considered persuasive as they did not address all the teachings of the art.
Conclusion
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/KRISTEN A DAGENAIS/Examiner, Art Unit 1717