DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
2. Applicant’s Amendment filed May 5, 2026 (hereinafter “05/05/26 Amendment") has been entered, and fully considered. In the 05/05/26 Amendment, claims 1, 3, 4, 6, & 7 were amended, and claims 5 & 11 were cancelled (claim 2 was previously cancelled). No claims were newly added. Accordingly, claims 1, 3, 4, 6-10, 12, & 13 are now pending in the application.
3. The 05/06/26 Amendment has overcome the claim objections previously set forth in the Non-Final Office Action mailed 02/05/26 (“02/05/26 Action”).
4. The cancellation of claims 5 & 11 has rendered the prior rejection of these claims under § 103 moot.
5. The rejection of claims 1, 3, 4, 6-10, 12, & 13 under § 103 previously set forth in the 02/05/26 Action has been updated to address the new limitations, and maintained.
6. Applicant's arguments are addressed in detail below in the “Response to Arguments” section.
Claim Rejections - 35 USC § 103
7. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
8. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
9. Claims 1, 3, 4, 6-10, 12, & 13 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 2014/0316387 to Harris et al. (“Harris”) in view of U.S. 2017/0304308 to Gendelman et al. (“Gendelman”), and further in view of U.S. Patent Application Publication No. 2012/0129916 to Peer ("Peer"), as evidenced by a publication to Ul-Islam et al., entitled “Antimicrobial and biocompatible properties of nanomaterials;” J. Nanosci. Nanotechnol.; © 2014, Vol. 14, No. 1; pgs. 780-791 (“Ul-Islam”).
10. Regarding claim 1, Harris teaches a method of treating a skin condition comprising:
obtaining a composition of opsonized [see note below] plasmonic sub-micron nanoparticles [e.g., ¶[0084] (“a composition comprises plasmonic nanoparticles”); see also ¶’s [0076], [0081], [0093], [0121], [0247], & [0262]] formulated for topical administration [Harris teaches topical administration - e.g., ¶’s [0010], [0023], [0028], [0043], [0069] (“"Administer" and "administration" as used herein, include providing or causing the provision of a material to a subject, such as by a topical, subdermal, subcutaneous, intradermal, enteral, parenteral, rectal, nasal, intravenous, intramuscularly, intraperitoneal, or other route”); [0070], [0102], [0103], [0125], [0130]] wherein… (2) said opsonized [see note below] plasmonic sub-micron nanoparticles are in a dermatologically acceptable carrier [e.g., ¶’s [0070], [0125] (“a cosmetically or pharmaceutically acceptable carrier”)], wherein the plasmonic sub-micron nanoparticles are opsonized… [NOTE: Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [e.g., ¶’s [0097], [0121], [0210], [0212], [0241], [0247], [0262]; Applicant’s Specification recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]; as such, coating of the particles with hyaluronic acid (or encapsulating the particles therein) in Harris reads on this claim limitation];
wherein said composition has a concentration of opsonized plasmonic sub-micron nanoparticles of between about 109 and 1014 particles per ml [e.g., ¶[0084] (“In various embodiments, a composition comprises plasmonic nanoparticles. In various embodiments, such compositions contain from about…109 and 1014 … particles per ml”)],
wherein said opsonized plasmonic sub-micron nanoparticles generate a surface plasmon [e.g., ¶’s [0024], [0081], [0115], [0116], [0118], [0229]] when irradiated with light having a wavelength between about 750 and 1200 nm [e.g., ¶[0011] (“irradiating the solution of unassembled plasmonic nanoparticles with an energy wavelength in a range of 750 nm to 1200 nm to induce a plurality of surface plasmons”); see also ¶[0115]];
and wherein said opsonized plasmonic sub-micron nanoparticles comprise silver, gold, nickel, copper, titanium, palladium, platinum, chromium, or titanium nitride [e.g., ¶[0095] (“In various embodiments, the nanoparticle is a metal (e.g., gold, silver), metallic composite (e.g., silver and silica, gold and silica), metal oxide (e.g. iron oxide, titanium oxide), metallic salt (e.g., potassium oxalate, strontium chloride), intermetallic (e.g., titanium aluminide, alnico), electric conductor (e.g., copper, aluminum), electric superconductor (e.g., yttrium barium copper oxide, bismuth strontium calcium copper oxide), electric semiconductor (e.g., silicon, germanium), dielectric (e.g., silica, plastic), or quantum dot (e.g., zinc sulfide, cadmium selenium). In non-limiting examples, the materials are gold, silver, nickel, platinum, titanium, palladium, silicon, galadium. Alternatively, the nanoparticle contains a composite including multiple metals (e.g., alloy), a metal and a dielectric, a metal and a semiconductor, or a metal, semiconductor and dielectric”)];
applying said opsonized plasmonic sub-micron nanoparticle composition to a skin surface having a condition to be treated [e.g., ¶[0103] (“target tissues for topical and dermatological applications include the surface of the skin, the epidermis and the dermis. Diseases or conditions suitable for treatment with topical and dermatological applications include acne, warts, fungal infections, psoriasis, scar removal, hair removal, hair growth, reduction of hypertrophic scars or keloids, skin inconsistencies (e.g. texture, color, tone, elasticity, hydration), and malignant or non-malignant skin tumors”)];
moving said opsonized plasmonic sub-micron nanoparticles in said applied composition from said skin surface into a plurality of epidermal appendages [e.g., ¶[0130] (“Provided herein are means to redistribute plasmonic particles and other compositions described herein from the skin surface to a component of dermal tissue including a hair follicle, a component of a hair follicle, a follicle infundibulum, a sebaceous gland, or a component of a sebaceous gland…”); see also ¶[0131]];
removing said opsonized plasmonic sub-micron nanoparticles remaining on said skin surface after a portion of said opsonized plasmonic sub-micron nanoparticles have been moved into the plurality of epidermal appendages [e.g., ¶’s [0159]-[0160]]; and
irradiating said opsonized plasmonic sub-micron nanoparticles in said plurality of epidermal appendages with a 1 ns - 200 ms pulse [e.g., ¶’s [0119], [0163]] of light having a wavelength between about 750 and 1200 nm [e.g., ¶[0011] (“irradiating the solution of unassembled plasmonic nanoparticles with an energy wavelength in a range of 750 nm to 1200 nm to induce a plurality of surface plasmons”); see also ¶[0115]].
A. PARTICLE SIZE
Concerning the “size” of the nanoparticles, claim 1 requires:
wherein (1) (a) a longest dimension of at least about 80% of said opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and (b) the longest dimension of at least about 95% of said opsonized plasmonic sub-micron nanoparticles is greater than 100 nm.
Harris teaches “an optimal particle size of 30-800 nm (e.g., 100-800 nm)” [see ¶[0247]; see also ¶’s [0085], [0190], [0262]].
While those skilled in the art will readily appreciate that reference to the "size" of a nanoparticle is typically to the length of the largest straight dimension of the nanoparticle (e.g., the size of a perfectly spherical nanoparticle is its diameter), Harris does not explicitly reference a “longest dimension,” nor the claimed percentages.
Gendelman, in a similar field of endeavor, relates to the delivery of therapeutics [e.g., ¶[0002]], and teaches that it was known to utilize nanoparticles having a longest dimension of about 50nm to about 800nm [see ¶[0029] (“For example, the diameter or longest dimension of the nanoparticle may be about 50 to about 800 nm. In a particular embodiment, the diameter or longest dimension of the nanoparticle is about 50 to about 750 nm, about 50 to about 500 nm, about 200 nm to about 500 nm, about 250 nm to about 350 nm, or about 300 nm to about 350 nm. The nanoparticles may be, for example, rod shaped, elongated rods, irregular, or round shaped”)].
As such, it is the Examiner’s position that Gendelman teaches a range that overlaps with Applicant’s claimed range, i.e., 100% of the nanoparticles in Gendelman haver a longest dimension that falls within 50-800 nm, while 95% of Applicant’s nanoparticles have a size greater than 100 nm and at least about 80% have a size of less than 800 nm.
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Harris such that a longest dimension of at least about 80% of said opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and the longest dimension of at least about 95% of said opsonized plasmonic sub-micron nanoparticles is greater than 100 nm, since it has been held that, 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).
B. OPSONIZED WITH KERATAN SULFATE OR CHONDROITIN SULFATE
As noted above, Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [this is consistent with Applicant’s Specification which recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]].
Harris does not, however, explicitly teach that:
[the particles are] opsonized with keratan sulfate or chondroitin sulfate.
Peer, in a similar field of endeavor, teaches that hyaluronic acid (HA), keratan sulfate, and chondroitin sulfate are all known examples of a glycosaminoglycan. More particularly, Peer teaches cell-targeting nanoparticles [¶[0001]] for targeting various different types of cancers [¶[0170]], as well as other diseases or viruses [e.g., ¶’s [0135], [0148]], and that a targeting moiety may comprise a glycosaminoglycan which can be selected from the group consisting of hyaluronic acid (HA), keratan sulfate, chondroitin sulfate, heparin sulfate, heparan sulfate, dermatin sulfate, salts, and mixtures thereof [¶’s [0022], [0043], [0044], [0146]-[0148]] for targeting any of a variety of cells [¶[0148]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to further modify Harris, which already teaches the use of a glycosaminoglycan (hyaluronic acid), to utilize any known, art-recognized glycosaminoglycan such as, e.g., keratan sulfate or chondroitin sulfate, since such a modification amounts merely to the simple substitution of one known glycosaminoglycan for another, yielding predictable results [opsinizing particles with a known glycosaminoglycan] to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
C. CAUSING BACTERIA TO INGEST THE PARTICLES
Claim 1 further recites the following emphasized claim limitations:
wherein the plasmonic sub-micron particles are opsonized with a glycosaminoglycan selected from keratan sulfate or chondroitin sulfate to cause bacteria to ingest the opsonized plasmonic sub-micron nanoparticles; [and]
allowing time for the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.
Harris further teaches that the invention may be used for the targeting of bacteria [see ¶[0022] (“In several embodiments of the invention, reduction of microorganisms, via the photoactive particles (e.g., plasmonic nanoparticles) described herein, include, but is not limited to, inactivation of bacteria or other microorganisms, reduction in the number, growth, viability, and/or function etc. of bacteria or other microorganisms. This reduction can be accomplished by, for example, the heat generated by several of the embodiments described herein and/or the enhanced delivery of drugs and other substances”); see also ¶’s [0137], [0178]].
Because the combination of Harris, Gendelman, & Peer teaches all of the other claimed method steps, it logically follows that the method of Harris, Gendelman, & Peer would therefore achieve the same result of causing the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.
Nonetheless, in the interest of compact prosecution, the antibacterial effects of nanomaterials, including the penetration of bacterial cells by nanoparticles (NPs), was clearly recognized and appreciated in the art, before the effective filing date of the claimed invention, a contention which (for completeness and clarity) is clearly established/evidenced by the disclosure of Ul-Islam - see § 4 (“Mechanism of Nanomaterial Antibacterial Activity”) and § 4.1 (“Interaction of Nanomaterials with the Cell Membrane”), at pgs. 784-785.
Finally, it is the Examiner’s position that the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, inherently includes the step of “allowing time for the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.” Again, as noted above, Harris teaches that the method is effective to, e.g., inactivate bacteria or other microorganisms and reduce the number, growth, viability, and/or function etc. of bacteria or other microorganisms [e.g., ¶’s [0022], [0137], [0178]]. As such, it is not clear how the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, could be effective against bacteria (as Harris states), if the bacteria were not allowed time to ingest the opsonized plasmonic sub-micron nanoparticles.
11. Regarding claim 3, Harris teaches a method of treating a skin condition comprising:
applying a composition formulated for topical administration [Harris teaches topical administration - e.g., ¶’s [0010], [0023], [0028], [0043], [0069] (“"Administer" and "administration" as used herein, include providing or causing the provision of a material to a subject, such as by a topical, subdermal, subcutaneous, intradermal, enteral, parenteral, rectal, nasal, intravenous, intramuscularly, intraperitoneal, or other route”); [0070], [0102], [0103], [0125], [0130]] of composite opsonized plasmonic sub-micron nanoparticles [e.g., ¶[0084] (“a composition comprises plasmonic nanoparticles”); see also ¶’s [0076], [0081], [0093], [0121], [0247], & [0262]; NOTE: Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [e.g., ¶’s [0097], [0121], [0210], [0212], [0241], [0247], [0262]; Applicant’s Specification recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]; as such, coating of the particles with hyaluronic acid (or encapsulating the particles therein) in Harris reads on this claim limitation] to a skin surface having a condition to be treated [e.g., ¶[0103] (“target tissues for topical and dermatological applications include the surface of the skin, the epidermis and the dermis. Diseases or conditions suitable for treatment with topical and dermatological applications include acne, warts, fungal infections, psoriasis, scar removal, hair removal, hair growth, reduction of hypertrophic scars or keloids, skin inconsistencies (e.g. texture, color, tone, elasticity, hydration), and malignant or non-malignant skin tumors”)];
wherein said composition has a concentration of composite opsonized plasmonic sub-micron nanoparticles of between about 109 and 1014 nanoparticles per ml [e.g., ¶[0084] (“In various embodiments, a composition comprises plasmonic nanoparticles. In various embodiments, such compositions contain from about…109 and 1014 … particles per ml”)];
wherein said composite opsonized plasmonic sub-micron nanoparticles comprise assembled [e.g., ¶[0090] (“In other embodiments, the nanoparticle compositions are assembled into ordered arrays. In particular, such ordered arrays can include any three dimensional array. In some embodiments, only a portion of the nanoparticles are assembled, e.g., 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 86, 90, 95, 99% or greater than 99% of the nanoparticles are assembled in an ordered array. The nanoparticles are assembled by a van der Walls attraction, a London force, a hydrogen bond, a dipole-dipole interaction, or a covalent bond, or a combination thereof”)] composite opsonized plasmonic sub-micron nanoparticles, …;
wherein said composite opsonized plasmonic sub-micron nanoparticles generate a surface plasmon [e.g., ¶’s [0024], [0081], [0115], [0116], [0118], [0229]] when irradiated with light having a wavelength between about 700 and 1200 nm [e.g., ¶[0011] (“irradiating the solution of unassembled plasmonic nanoparticles with an energy wavelength in a range of 750 nm to 1200 nm to induce a plurality of surface plasmons”); see also ¶[0115]]; [and]
wherein said composite opsonized plasmonic sub-micron nanoparticles comprise silver, gold, nickel, copper, titanium, silicon, gallium, palladium, platinum, chromium, or titanium nitride [e.g., ¶[0095] (“In various embodiments, the nanoparticle is a metal (e.g., gold, silver), metallic composite (e.g., silver and silica, gold and silica), metal oxide (e.g. iron oxide, titanium oxide), metallic salt (e.g., potassium oxalate, strontium chloride), intermetallic (e.g., titanium aluminide, alnico), electric conductor (e.g., copper, aluminum), electric superconductor (e.g., yttrium barium copper oxide, bismuth strontium calcium copper oxide), electric semiconductor (e.g., silicon, germanium), dielectric (e.g., silica, plastic), or quantum dot (e.g., zinc sulfide, cadmium selenium). In non-limiting examples, the materials are gold, silver, nickel, platinum, titanium, palladium, silicon, galadium. Alternatively, the nanoparticle contains a composite including multiple metals (e.g., alloy), a metal and a dielectric, a metal and a semiconductor, or a metal, semiconductor and dielectric”)]; and
A. PARTICLE SIZE
Concerning the “size” of the nanoparticles, claim 3 requires:
wherein a longest dimension of at least about 80% of said assembled opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and (b) the longest dimension of at least about 95% of said assembled opsonized plasmonic sub-micron nanoparticles is greater than 100 nm.
Harris teaches “an optimal particle size of 30-800 nm (e.g., 100-800 nm)” [see ¶[0247]; see also ¶’s [0085], [0190], [0262]].
While those skilled in the art will readily appreciate that reference to the "size" of a nanoparticle is typically to the length of the largest straight dimension of the nanoparticle (e.g., the size of a perfectly spherical nanoparticle is its diameter), Harris does not explicitly reference a “longest dimension,” nor the claimed percentages.
Gendelman, in a similar field of endeavor, relates to the delivery of therapeutics [e.g., ¶[0002]], and teaches that it was known to utilize nanoparticles having a longest dimension of about 50nm to about 800nm [see ¶[0029] (“For example, the diameter or longest dimension of the nanoparticle may be about 50 to about 800 nm. In a particular embodiment, the diameter or longest dimension of the nanoparticle is about 50 to about 750 nm, about 50 to about 500 nm, about 200 nm to about 500 nm, about 250 nm to about 350 nm, or about 300 nm to about 350 nm. The nanoparticles may be, for example, rod shaped, elongated rods, irregular, or round shaped”)].
As such, it is the Examiner’s position that Gendelman teaches a range that overlaps with Applicant’s claimed range, i.e., 100% of the nanoparticles in Gendelman haver a longest dimension that falls within 50-800 nm, while 95% of Applicant’s nanoparticles have a size greater than 100 nm and at least about 80% have a size of less than 800 nm.
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Harris such that a longest dimension of at least about 80% of said assembled opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and the longest dimension of at least about 95% of said assembled opsonized plasmonic sub-micron nanoparticles is greater than 100 nm, since it has been held that, 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).
B. OPSONIZED WITH KERATAN SULFATE OR CHONDROITIN SULFATE
As noted above, Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [this is consistent with Applicant’s Specification which recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]].
Harris does not, however, explicitly teach:
wherein said composite opsonized plasmonic sub-micron nanoparticles are coated with keratan sulfate or chondroitin sulfate.
Peer, in a similar field of endeavor, teaches that hyaluronic acid (HA), keratan sulfate, and chondroitin sulfate are all known examples of a glycosaminoglycan. More particularly, Peer teaches cell-targeting nanoparticles [¶[0001]] for targeting various different types of cancers [¶[0170]], as well as other diseases or viruses [e.g., ¶’s [0135], [0148]], and that a targeting moiety may comprise a glycosaminoglycan which can be selected from the group consisting of hyaluronic acid (HA), keratan sulfate, chondroitin sulfate, heparin sulfate, heparan sulfate, dermatin sulfate, salts, and mixtures thereof [¶’s [0022], [0043], [0044], [0146]-[0148]] for targeting any of a variety of cells [¶[0148]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Harris, which already teaches the use of a glycosaminoglycan (hyaluronic acid), to utilize any known, art-recognized glycosaminoglycan such as, e.g., keratan sulfate or chondroitin sulfate, since such a modification amounts merely to the simple substitution of one known glycosaminoglycan for another, yielding predictable results [opsinizing particles with a known glycosaminoglycan] to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
C. CAUSING BACTERIA TO INGEST THE PARTICLES
Claim 3 further recites the following claim limitation:
allowing time for the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.
First, as it concerns ingestion of the opsonized plasmonic sub-micron nanoparticles by the bacteria, Harris further teaches that the invention may be used for the targeting of bacteria [see ¶[0022] (“In several embodiments of the invention, reduction of microorganisms, via the photoactive particles (e.g., plasmonic nanoparticles) described herein, include, but is not limited to, inactivation of bacteria or other microorganisms, reduction in the number, growth, viability, and/or function etc. of bacteria or other microorganisms. This reduction can be accomplished by, for example, the heat generated by several of the embodiments described herein and/or the enhanced delivery of drugs and other substances”); see also ¶’s [0137], [0178]].
Because the combination of Harris, Gendelman, & Peer teaches all of the other claimed method steps, it logically follows that the method of Harris, Gendelman, & Peer would therefore achieve the same result of allowing the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.
Nonetheless, in the interest of compact prosecution, the antibacterial effects of nanomaterials, including the penetration of bacterial cells by nanoparticles (NPs), was clearly recognized and appreciated in the art, before the effective filing date of the claimed invention, a contention which (for completeness and clarity) is clearly established/evidenced by the disclosure of Ul-Islam - see § 4 (“Mechanism of Nanomaterial Antibacterial Activity”) and § 4.1 (“Interaction of Nanomaterials with the Cell Membrane”), at pgs. 784-785.
Finally, it is the Examiner’s position that the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, inherently includes the step of “allowing time for the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.” Again, as noted above, Harris teaches that the method is effective to, e.g., inactivate bacteria or other microorganisms and reduce the number, growth, viability, and/or function etc. of bacteria or other microorganisms [e.g., ¶’s [0022], [0137], [0178]]. As such, it is not clear how the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, could be effective against bacteria (as Harris states), if the bacteria were not allowed time to ingest the opsonized plasmonic sub-micron nanoparticles.
12. Regarding claim 4, Harris teaches a method of treating a skin condition comprising:
obtaining a composition of composite opsonized [see note below] plasmonic sub-micron nanoparticles [e.g., ¶[0084] (“a composition comprises plasmonic nanoparticles”); see also ¶’s [0076], [0081], [0093], [0121], [0247], & [0262]];
wherein said composition has a concentration of composite opsonized [see note below] plasmonic sub-micron nanoparticles of between about 109 and 1014 nanoparticles per ml [e.g., ¶[0084] (“In various embodiments, a composition comprises plasmonic nanoparticles. In various embodiments, such compositions contain from about…109 and 1014 … particles per ml”)], wherein the composite plasmonic sub-micron nanoparticles are opsonized… [NOTE: Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [e.g., ¶’s [0097], [0121], [0210], [0212], [0241], [0247], [0262]; Applicant’s Specification recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]; as such, coating of the particles with hyaluronic acid (or encapsulating the particles therein) in Harris reads on this claim limitation];
applying the composition to a skin surface having a condition to be treated [e.g., ¶[0103] (“target tissues for topical and dermatological applications include the surface of the skin, the epidermis and the dermis. Diseases or conditions suitable for treatment with topical and dermatological applications include acne, warts, fungal infections, psoriasis, scar removal, hair removal, hair growth, reduction of hypertrophic scars or keloids, skin inconsistencies (e.g. texture, color, tone, elasticity, hydration), and malignant or non-malignant skin tumors”)];
wherein said composite opsonized plasmonic sub-micron nanoparticles comprise assembled [e.g., ¶[0090] (“In other embodiments, the nanoparticle compositions are assembled into ordered arrays. In particular, such ordered arrays can include any three dimensional array. In some embodiments, only a portion of the nanoparticles are assembled, e.g., 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 86, 90, 95, 99% or greater than 99% of the nanoparticles are assembled in an ordered array. The nanoparticles are assembled by a van der Walls attraction, a London force, a hydrogen bond, a dipole-dipole interaction, or a covalent bond, or a combination thereof”)] composite opsonized plasmonic sub-micron nanoparticles,…,
wherein said composite opsonized plasmonic sub-micron nanoparticles generate a surface plasmon e.g., ¶’s [0024], [0081], [0115], [0116], [0118], [0229]] when irradiated with light having a wavelength between about 700 and 1200 nm [e.g., ¶[0011] (“irradiating the solution of unassembled plasmonic nanoparticles with an energy wavelength in a range of 750 nm to 1200 nm to induce a plurality of surface plasmons”); see also ¶[0115]]; and
wherein said composite opsonized plasmonic sub-micron nanoparticles comprise silver, gold, nickel, copper, titanium, palladium, platinum, chromium, or titanium nitride [e.g., ¶[0095] (“In various embodiments, the nanoparticle is a metal (e.g., gold, silver), metallic composite (e.g., silver and silica, gold and silica), metal oxide (e.g. iron oxide, titanium oxide), metallic salt (e.g., potassium oxalate, strontium chloride), intermetallic (e.g., titanium aluminide, alnico), electric conductor (e.g., copper, aluminum), electric superconductor (e.g., yttrium barium copper oxide, bismuth strontium calcium copper oxide), electric semiconductor (e.g., silicon, germanium), dielectric (e.g., silica, plastic), or quantum dot (e.g., zinc sulfide, cadmium selenium). In non-limiting examples, the materials are gold, silver, nickel, platinum, titanium, palladium, silicon, galadium. Alternatively, the nanoparticle contains a composite including multiple metals (e.g., alloy), a metal and a dielectric, a metal and a semiconductor, or a metal, semiconductor and dielectric”)].
A. PARTICLE SIZE
Concerning the “size” of the nanoparticles, claim 4 requires:
wherein (a) a longest dimension of at least about 80% of said assembled opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and (b) the longest dimension of at least about 95% of said assembled opsonized plasmonic sub-micron nanoparticles is greater than 100 nm.
Harris teaches “an optimal particle size of 30-800 nm (e.g., 100-800 nm)” [see ¶[0247]; see also ¶’s [0085], [0190], [0262]].
While those skilled in the art will readily appreciate that reference to the "size" of a nanoparticle is typically to the length of the largest straight dimension of the nanoparticle (e.g., the size of a perfectly spherical nanoparticle is its diameter), Harris does not explicitly reference a “longest dimension,” nor the claimed percentages.
Gendelman, in a similar field of endeavor, relates to the delivery of therapeutics [e.g., ¶[0002]], and teaches that it was known to utilize nanoparticles having a longest dimension of about 50nm to about 800nm [see ¶[0029] (“For example, the diameter or longest dimension of the nanoparticle may be about 50 to about 800 nm. In a particular embodiment, the diameter or longest dimension of the nanoparticle is about 50 to about 750 nm, about 50 to about 500 nm, about 200 nm to about 500 nm, about 250 nm to about 350 nm, or about 300 nm to about 350 nm. The nanoparticles may be, for example, rod shaped, elongated rods, irregular, or round shaped”)].
As such, it is the Examiner’s position that Gendelman teaches a range that overlaps with Applicant’s claimed range, i.e., 100% of the nanoparticles in Gendelman haver a longest dimension that falls within 50-800 nm, while 95% of Applicant’s nanoparticles have a size greater than 100 nm and at least about 80% have a size of less than 800 nm.
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Harris such that the longest dimension of at least about 80% of said assembled opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and the longest dimension of at least about 95% of said assembled opsonized plasmonic sub-micron nanoparticles is greater than 100 nm, since it has been held that, 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).
B. OPSONIZED WITH KERATAN SULFATE OR CHONDROITIN SULFATE
As noted above, Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [this is consistent with Applicant’s Specification which recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]].
Harris does not, however, explicitly teach that:
[the particles are] opsonized with keratan sulfate or chondroitin sulfate.
Peer, in a similar field of endeavor, teaches that hyaluronic acid (HA), keratan sulfate, and chondroitin sulfate are all known examples of a glycosaminoglycan. More particularly, Peer teaches cell-targeting nanoparticles [¶[0001]] for targeting various different types of cancers [¶[0170]], as well as other diseases or viruses [e.g., ¶’s [0135], [0148]], and that a targeting moiety may comprise a glycosaminoglycan which can be selected from the group consisting of hyaluronic acid (HA), keratan sulfate, chondroitin sulfate, heparin sulfate, heparan sulfate, dermatin sulfate, salts, and mixtures thereof [¶’s [0022], [0043], [0044], [0146]-[0148]] for targeting any of a variety of cells [¶[0148]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Harris, which already teaches the use of a glycosaminoglycan (hyaluronic acid), to utilize any known, art-recognized glycosaminoglycan such as, e.g., keratan sulfate or chondroitin sulfate, since such a modification amounts merely to the simple substitution of one known glycosaminoglycan for another, yielding predictable results [opsinizing particles with a known glycosaminoglycan] to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
C. ALLOWING BACTERIA TO INGEST THE PARTICLES
Claim 4 further recites the following emphasized claim limitations:
wherein the opsonized plasmonic sub-micron nanoparticles are opsonized with a glycosaminoglycan selected from keratan sulfate or chondroitin sulfate to cause bacteria to ingest the opsonized plasmonic sub-micron nanoparticles; [and]
allowing time for the bacteria to ingest the composite opsonized plasmonic sub-micron nanoparticles.
Harris further teaches that the invention may be used for the targeting of bacteria [see ¶[0022] (“In several embodiments of the invention, reduction of microorganisms, via the photoactive particles (e.g., plasmonic nanoparticles) described herein, include, but is not limited to, inactivation of bacteria or other microorganisms, reduction in the number, growth, viability, and/or function etc. of bacteria or other microorganisms. This reduction can be accomplished by, for example, the heat generated by several of the embodiments described herein and/or the enhanced delivery of drugs and other substances”); see also ¶’s [0137], [0178]].
Because the combination of Harris, Gendelman, & Peer teaches all of the other claimed method steps, it logically follows that the method of Harris, Gendelman, & Peer would therefore achieve the same result of allowing the bacteria to ingest the composite opsonized plasmonic sub-micron nanoparticles.
Nonetheless, in the interest of compact prosecution, the antibacterial effects of nanomaterials, including the penetration of bacterial cells by nanoparticles (NPs), was clearly recognized and appreciated in the art, before the effective filing date of the claimed invention, a contention which (for completeness and clarity) is clearly established/evidenced by the disclosure of Ul-Islam - see § 4 (“Mechanism of Nanomaterial Antibacterial Activity”) and § 4.1 (“Interaction of Nanomaterials with the Cell Membrane”), at pgs. 784-785.
Finally, it is the Examiner’s position that the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, inherently includes the step of “allowing time for the bacteria to ingest the composite opsonized plasmonic sub-micron nanoparticles.” Again, as noted above, Harris teaches that the method is effective to, e.g., inactivate bacteria or other microorganisms and reduce the number, growth, viability, and/or function etc. of bacteria or other microorganisms [e.g., ¶’s [0022], [0137], [0178]]. As such, it is not clear how the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, could be effective against bacteria (as Harris states), if the bacteria were not allowed time to ingest the composite opsonized plasmonic sub-micron nanoparticles.
13. Regarding claim 6, Harris teaches a method of treating a skin condition in need of treatment, said method comprising:
obtaining a suspension formulated for topical administration [Harris teaches topical administration - e.g., ¶’s [0010], [0023], [0028], [0043], [0069] (“"Administer" and "administration" as used herein, include providing or causing the provision of a material to a subject, such as by a topical, subdermal, subcutaneous, intradermal, enteral, parenteral, rectal, nasal, intravenous, intramuscularly, intraperitoneal, or other route”); [0070], [0102], [0103], [0125], [0130]] of opsonized [see note below] plasmonic sub-micron nanoparticles [e.g., ¶[0084] (“a composition comprises plasmonic nanoparticles”); see also ¶’s [0076], [0081], [0093], [0121], [0247], & [0262]] dispersed in a dermatologically acceptable carrier [e.g., ¶’s [0070], [0125] (“a cosmetically or pharmaceutically acceptable carrier”)],…, wherein the plasmonic sub-micron nanoparticles are opsonized… [NOTE: Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [e.g., ¶’s [0097], [0121], [0210], [0212], [0241], [0247], [0262]; Applicant’s Specification recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]; as such, coating of the particles with hyaluronic acid (or encapsulating the particles therein) in Harris reads on this claim limitation];
wherein an exterior of said opsonized plasmonic sub-micron nanoparticles is a coating [e.g., ¶’s [0052], [0096], [0097] (see TABLE), [0193], [0282]] that comprises at least one member of the group consisting of polyethylene glycol (PEG) [¶[0052]], silica, silica-oxide, polyvinylpyrrolidone, polystyrene, silica, silver, polyvinylpyrrolidone (PVP), cetyl trimethylammonium bromide (CTAB), citrate, lipoic acid, short chain polyethylenimine (PI) and branched polyethylenimine, reduced graphene oxide, a protein, a peptide, and a glycosaminoglycan [see also ¶’s [0086], [0097] (see TABLE), [0193], [0282]],
wherein said suspension has a concentration of opsonized plasmonic sub-micron nanoparticles of between about 109 and 1014 particles per ml [e.g., ¶[0084] (“In various embodiments, a composition comprises plasmonic nanoparticles. In various embodiments, such compositions contain from about…109 and 1014 … particles per ml”)],
wherein said opsonized plasmonic sub-micron nanoparticles generate a surface plasmon [e.g., ¶’s [0024], [0081], [0115], [0116], [0118], [0229]] when irradiated with light having a wavelength between about 750 and 1200 nm [e.g., ¶[0011] (“irradiating the solution of unassembled plasmonic nanoparticles with an energy wavelength in a range of 750 nm to 1200 nm to induce a plurality of surface plasmons”); see also ¶[0115]];
wherein said opsonized plasmonic sub-micron nanoparticles comprise silver, gold, nickel, copper, titanium, palladium, platinum, chromium, or titanium nitride [e.g., ¶[0095] (“In various embodiments, the nanoparticle is a metal (e.g., gold, silver), metallic composite (e.g., silver and silica, gold and silica), metal oxide (e.g. iron oxide, titanium oxide), metallic salt (e.g., potassium oxalate, strontium chloride), intermetallic (e.g., titanium aluminide, alnico), electric conductor (e.g., copper, aluminum), electric superconductor (e.g., yttrium barium copper oxide, bismuth strontium calcium copper oxide), electric semiconductor (e.g., silicon, germanium), dielectric (e.g., silica, plastic), or quantum dot (e.g., zinc sulfide, cadmium selenium). In non-limiting examples, the materials are gold, silver, nickel, platinum, titanium, palladium, silicon, galadium. Alternatively, the nanoparticle contains a composite including multiple metals (e.g., alloy), a metal and a dielectric, a metal and a semiconductor, or a metal, semiconductor and dielectric”)];
applying said opsonized plasmonic sub-micron nanoparticle suspension to a skin surface having a condition to be treated [e.g., ¶[0103] (“target tissues for topical and dermatological applications include the surface of the skin, the epidermis and the dermis. Diseases or conditions suitable for treatment with topical and dermatological applications include acne, warts, fungal infections, psoriasis, scar removal, hair removal, hair growth, reduction of hypertrophic scars or keloids, skin inconsistencies (e.g. texture, color, tone, elasticity, hydration), and malignant or non-malignant skin tumors”)];
moving said opsonized plasmonic sub-micron nanoparticles in said applied composition from said skin surface into a plurality of epidermal appendages [e.g., ¶[0130] (“Provided herein are means to redistribute plasmonic particles and other compositions described herein from the skin surface to a component of dermal tissue including a hair follicle, a component of a hair follicle, a follicle infundibulum, a sebaceous gland, or a component of a sebaceous gland…”); see also ¶[0131]];
removing said opsonized plasmonic sub-micron nanoparticles remaining on said skin surface after a portion of said opsonized plasmonic sub-micron nanoparticles have been moved into the plurality of epidermal appendages [e.g., ¶’s [0159]-[0160]]; and
irradiating said opsonized plasmonic sub-micron nanoparticles in said plurality of epidermal appendages with a 1 ns - 200 ms pulse [e.g., ¶’s [0119], [0163]] of light having a wavelength between about 750 and 1200 nm [e.g., ¶[0011] (“irradiating the solution of unassembled plasmonic nanoparticles with an energy wavelength in a range of 750 nm to 1200 nm to induce a plurality of surface plasmons”); see also ¶[0115]].
A. PARTICLE SIZE
Concerning the “size” of the nanoparticles, claim 6 requires:
wherein (1) (a) the longest dimension of at least about 80% of said opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and (b) the longest dimension of at least about 95% of said opsonized plasmonic sub-micron nanoparticles is greater than 100 nm.
Harris teaches “an optimal particle size of 30-800 nm (e.g., 100-800 nm)” [see ¶[0247]; see also ¶’s [0085], [0190], [0262]].
While those skilled in the art will readily appreciate that reference to the "size" of a nanoparticle is typically to the length of the largest straight dimension of the nanoparticle (e.g., the size of a perfectly spherical nanoparticle is its diameter), Harris does not explicitly reference a “longest dimension,” nor the claimed percentages.
Gendelman, in a similar field of endeavor, relates to the delivery of therapeutics [e.g., ¶[0002]], and teaches that it was known to utilize nanoparticles having a longest dimension of about 50nm to about 800nm [see ¶[0029] (“For example, the diameter or longest dimension of the nanoparticle may be about 50 to about 800 nm. In a particular embodiment, the diameter or longest dimension of the nanoparticle is about 50 to about 750 nm, about 50 to about 500 nm, about 200 nm to about 500 nm, about 250 nm to about 350 nm, or about 300 nm to about 350 nm. The nanoparticles may be, for example, rod shaped, elongated rods, irregular, or round shaped”)].
As such, it is the Examiner’s position that Gendelman teaches a range that overlaps with Applicant’s claimed range, i.e., 100% of the nanoparticles in Gendelman haver a longest dimension that falls within 50-800 nm, while 95% of Applicant’s nanoparticles have a size greater than 100 nm and at least about 80% have a size of less than 800 nm.
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Harris such that the longest dimension of at least about 80% of said opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and the longest dimension of at least about 95% of said opsonized plasmonic sub-micron nanoparticles is greater than 100 nm, since it has been held that, 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).
B. OPSONIZED WITH KERATAN SULFATE OR CHONDROITIN SULFATE
As noted above, Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [this is consistent with Applicant’s Specification which recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]].
Harris does not, however, explicitly teach that:
[the particles are] opsonized with keratan sulfate or chondroitin sulfate.
Peer, in a similar field of endeavor, teaches that hyaluronic acid (HA), keratan sulfate, and chondroitin sulfate are all known examples of a glycosaminoglycan. More particularly, Peer teaches cell-targeting nanoparticles [¶[0001]] for targeting various different types of cancers [¶[0170]], as well as other diseases or viruses [e.g., ¶’s [0135], [0148]], and that a targeting moiety may comprise a glycosaminoglycan which can be selected from the group consisting of hyaluronic acid (HA), keratan sulfate, chondroitin sulfate, heparin sulfate, heparan sulfate, dermatin sulfate, salts, and mixtures thereof [¶’s [0022], [0043], [0044], [0146]-[0148]] for targeting any of a variety of cells [¶[0148]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Harris, which already teaches the use of a glycosaminoglycan (hyaluronic acid), to utilize any known, art-recognized glycosaminoglycan such as, e.g., keratan sulfate or chondroitin sulfate, since such a modification amounts merely to the simple substitution of one known glycosaminoglycan for another, yielding predictable results [opsinizing particles with a known glycosaminoglycan] to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
C. CAUSING BACTERIA TO INGEST THE PARTICLES
Claim 6 further recites the following emphasized claim limitations:
… to cause bacteria to ingest the opsonized plasmonic sub-micron nanoparticles; [and]
allowing time for the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.
Harris further teaches that the invention may be used for the targeting of bacteria [see ¶[0022] (“In several embodiments of the invention, reduction of microorganisms, via the photoactive particles (e.g., plasmonic nanoparticles) described herein, include, but is not limited to, inactivation of bacteria or other microorganisms, reduction in the number, growth, viability, and/or function etc. of bacteria or other microorganisms. This reduction can be accomplished by, for example, the heat generated by several of the embodiments described herein and/or the enhanced delivery of drugs and other substances”); see also ¶’s [0137], [0178]].
Because the combination of Harris, Gendelman, & Peer teaches all of the other claimed method steps, it logically follows that the method of Harris, Gendelman, & Peer would therefore achieve the same result of causing the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.
Nonetheless, in the interest of compact prosecution, the antibacterial effects of nanomaterials, including the penetration of bacterial cells by nanoparticles (NPs), was clearly recognized and appreciated in the art, before the effective filing date of the claimed invention, a contention which (for completeness and clarity) is clearly established/evidenced by the disclosure of Ul-Islam - see § 4 (“Mechanism of Nanomaterial Antibacterial Activity”) and § 4.1 (“Interaction of Nanomaterials with the Cell Membrane”), at pgs. 784-785.
Finally, it is the Examiner’s position that the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, inherently includes the step of “allowing time for the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.” Again, as noted above, Harris teaches that the method is effective to, e.g., inactivate bacteria or other microorganisms and reduce the number, growth, viability, and/or function etc. of bacteria or other microorganisms [e.g., ¶’s [0022], [0137], [0178]]. As such, it is not clear how the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, could be effective against bacteria (as Harris states), if the bacteria were not allowed time to ingest the opsonized plasmonic sub-micron nanoparticles.
14. Regarding claim 7, Harris teaches a method of treating a skin condition in need of treatment, said method comprising:
obtaining a suspension formulated for topical administration [Harris teaches topical administration - e.g., ¶’s [0010], [0023], [0028], [0043], [0069] (“"Administer" and "administration" as used herein, include providing or causing the provision of a material to a subject, such as by a topical, subdermal, subcutaneous, intradermal, enteral, parenteral, rectal, nasal, intravenous, intramuscularly, intraperitoneal, or other route”); [0070], [0102], [0103], [0125], [0130]] of opsonized [see note below] plasmonic sub-micron nanoparticles [e.g., ¶[0084] (“a composition comprises plasmonic nanoparticles”); see also ¶’s [0076], [0081], [0093], [0121], [0247], & [0262]] dispersed in a dermatologically acceptable carrier [e.g., ¶’s [0070], [0125] (“a cosmetically or pharmaceutically acceptable carrier”)], wherein the plasmonic sub-micron nanoparticles are opsonized… [NOTE: Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [e.g., ¶’s [0097], [0121], [0210], [0212], [0241], [0247], [0262]; Applicant’s Specification recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]; as such, coating of the particles with hyaluronic acid (or encapsulating the particles therein) in Harris reads on this claim limitation];
wherein said opsonized plasmonic sub-micron nanoparticles comprise a conductive metal [e.g., ¶[0095]] and an exterior coating [e.g., ¶’s [0052], [0096], [0097] (see TABLE), [0193], [0282]];
wherein said conductive metal comprises at least one metal selected from the group consisting of silver, gold, nickel, copper, titanium, palladium, platinum, chromium, and titanium nitride [e.g., ¶[0095] (“In various embodiments, the nanoparticle is a metal (e.g., gold, silver), metallic composite (e.g., silver and silica, gold and silica), metal oxide (e.g. iron oxide, titanium oxide), metallic salt (e.g., potassium oxalate, strontium chloride), intermetallic (e.g., titanium aluminide, alnico), electric conductor (e.g., copper, aluminum), electric superconductor (e.g., yttrium barium copper oxide, bismuth strontium calcium copper oxide), electric semiconductor (e.g., silicon, germanium), dielectric (e.g., silica, plastic), or quantum dot (e.g., zinc sulfide, cadmium selenium). In non-limiting examples, the materials are gold, silver, nickel, platinum, titanium, palladium, silicon, galadium. Alternatively, the nanoparticle contains a composite including multiple metals (e.g., alloy), a metal and a dielectric, a metal and a semiconductor, or a metal, semiconductor and dielectric”)];
wherein said exterior coating comprises at least one member of the group consisting of polyethylene glycol (PEG) [¶[0052]], silica, silica-oxide, polyvinylpyrrolidone, polystyrene, silica, silver, polyvinylpyrrolidone (PVP), cetyl trimethylammonium bromide (CTAB), citrate, lipoic acid, short chain polyethylenimine (PI) and branched polyethylenimine, reduced graphene oxide, a protein, a peptide, and a glycosaminoglycan [see also ¶’s [0086], [0097] (see TABLE), [0193], [0282]];
wherein said suspension has a concentration of opsonized plasmonic sub-micron nanoparticles of between about 109 and 1014 particles per ml [e.g., ¶[0084] (“In various embodiments, a composition comprises plasmonic nanoparticles. In various embodiments, such compositions contain from about…109 and 1014 … particles per ml”)],
applying said opsonized plasmonic sub-micron nanoparticle suspension as an aerosol [e.g., ¶[0129] (“In some embodiments, the nanoparticle formulations (e.g., photoactive nanoparticles, such as plasmonic nanoparticles) are formulated for application by a sponge applicator, cloth applicator, direct contact via a hand or gloved hand, spray, aerosol…”)] to a skin surface having a condition to be treated [e.g., ¶[0103] (“target tissues for topical and dermatological applications include the surface of the skin, the epidermis and the dermis. Diseases or conditions suitable for treatment with topical and dermatological applications include acne, warts, fungal infections, psoriasis, scar removal, hair removal, hair growth, reduction of hypertrophic scars or keloids, skin inconsistencies (e.g. texture, color, tone, elasticity, hydration), and malignant or non-malignant skin tumors”)]; and
irradiating said opsonized plasmonic sub-micron nanoparticle suspension applied to said skin surface with a 1 ns - 200 ms pulse [e.g., ¶’s [0119], [0163]] of light having a wavelength between about 750 and 1200 nm [e.g., ¶[0011] (“irradiating the solution of unassembled plasmonic nanoparticles with an energy wavelength in a range of 750 nm to 1200 nm to induce a plurality of surface plasmons”); see also ¶[0115]].
A. PARTICLE SIZE
Concerning the “size” of the nanoparticles, claim 7 requires:
wherein (a) a longest dimension of at least about 80% of said opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and (b) the longest dimension of at least about 95% of said opsonized plasmonic sub-micron nanoparticles is greater than 100 nm.
Harris teaches “an optimal particle size of 30-800 nm (e.g., 100-800 nm)” [see ¶[0247]; see also ¶’s [0085], [0190], [0262]].
While those skilled in the art will readily appreciate that reference to the "size" of a nanoparticle is typically to the length of the largest straight dimension of the nanoparticle (e.g., the size of a perfectly spherical nanoparticle is its diameter), Harris does not explicitly reference a “longest dimension,” nor the claimed percentages.
Gendelman, in a similar field of endeavor, relates to the delivery of therapeutics [e.g., ¶[0002]], and teaches that it was known to utilize nanoparticles having a longest dimension of about 50nm to about 800nm [see ¶[0029] (“For example, the diameter or longest dimension of the nanoparticle may be about 50 to about 800 nm. In a particular embodiment, the diameter or longest dimension of the nanoparticle is about 50 to about 750 nm, about 50 to about 500 nm, about 200 nm to about 500 nm, about 250 nm to about 350 nm, or about 300 nm to about 350 nm. The nanoparticles may be, for example, rod shaped, elongated rods, irregular, or round shaped”)].
As such, it is the Examiner’s position that Gendelman teaches a range that overlaps with Applicant’s claimed range, i.e., 100% of the nanoparticles in Gendelman haver a longest dimension that falls within 50-800 nm, while 95% of Applicant’s nanoparticles have a size greater than 100 nm and at least about 80% have a size of less than 800 nm.
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Harris such that the longest dimension of at least about 80% of said opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and the longest dimension of at least about 95% of said opsonized plasmonic sub-micron nanoparticles is greater than 100 nm, since it has been held that, 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).
B. OPSONIZED WITH KERATAN SULFATE OR CHONDROITIN SULFATE
As noted above, Harris teaches that the particles are opsonized, in that they are coated with, or encapsulated in, hyaluronic acid, which is a known glycosaminoglycan [this is consistent with Applicant’s Specification which recites that “the plasmonic sub-micron particles are opsonized by functionalizing said particles with a glycosaminoglycan” (emphasis added) - see Applicant’s published Specification (U.S. 2018/0325594, published Nov. 15, 2018) at ¶[0117]].
Harris does not, however, explicitly teach that:
[the particles are] opsonized with keratan sulfate or chondroitin sulfate.
Peer, in a similar field of endeavor, teaches that hyaluronic acid (HA), keratan sulfate, and chondroitin sulfate are all known examples of a glycosaminoglycan. More particularly, Peer teaches cell-targeting nanoparticles [¶[0001]] for targeting various different types of cancers [¶[0170]], as well as other diseases or viruses [e.g., ¶’s [0135], [0148]], and that a targeting moiety may comprise a glycosaminoglycan which can be selected from the group consisting of hyaluronic acid (HA), keratan sulfate, chondroitin sulfate, heparin sulfate, heparan sulfate, dermatin sulfate, salts, and mixtures thereof [¶’s [0022], [0043], [0044], [0146]-[0148]] for targeting any of a variety of cells [¶[0148]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Harris, which already teaches the use of a glycosaminoglycan (hyaluronic acid), to utilize any known, art-recognized glycosaminoglycan such as, e.g., keratan sulfate or chondroitin sulfate, since such a modification amounts merely to the simple substitution of one known glycosaminoglycan for another, yielding predictable results [opsinizing particles with a known glycosaminoglycan] to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
C. CAUSING BACTERIA TO INGEST THE PARTICLES
Claim 7 further recites the following emphasized claim limitations:
wherein the plasmonic sub-micron nanoparticles are opsonized with a glycosaminoglycan selected from keratan sulfate or chondroitin sulfate to cause bacteria to ingest the opsonized plasmonic sub-micron nanoparticles; [and]
allowing time for the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.
Harris further teaches that the invention may be used for the targeting of bacteria [see ¶[0022] (“In several embodiments of the invention, reduction of microorganisms, via the photoactive particles (e.g., plasmonic nanoparticles) described herein, include, but is not limited to, inactivation of bacteria or other microorganisms, reduction in the number, growth, viability, and/or function etc. of bacteria or other microorganisms. This reduction can be accomplished by, for example, the heat generated by several of the embodiments described herein and/or the enhanced delivery of drugs and other substances”); see also ¶’s [0137], [0178]].
Because the combination of Harris, Gendelman, & Peer teaches all of the other claimed method steps, it logically follows that the method of Harris, Gendelman, & Peer would therefore achieve the same result of causing/allowing the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.
Nonetheless, in the interest of compact prosecution, the antibacterial effects of nanomaterials, including the penetration of bacterial cells by nanoparticles (NPs), was clearly recognized and appreciated in the art, before the effective filing date of the claimed invention, a contention which (for completeness and clarity) is clearly established/evidenced by the disclosure of Ul-Islam - see § 4 (“Mechanism of Nanomaterial Antibacterial Activity”) and § 4.1 (“Interaction of Nanomaterials with the Cell Membrane”), at pgs. 784-785.
Finally, it is the Examiner’s position that the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, inherently includes the step of “allowing time for the bacteria to ingest the opsonized plasmonic sub-micron nanoparticles.” Again, as noted above, Harris teaches that the method is effective to, e.g., inactivate bacteria or other microorganisms and reduce the number, growth, viability, and/or function etc. of bacteria or other microorganisms [e.g., ¶’s [0022], [0137], [0178]]. As such, it is not clear how the method of Harris, Gendelman, & Peer, as evidenced by Ul-Islam, could be effective against bacteria (as Harris states), if the bacteria were not allowed time to ingest the opsonized plasmonic sub-micron nanoparticles.
15. Regarding claim 8, the combination of Harris, Gendelman, and Peer, as evidenced by Ul-Islam, teaches all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Harris (as modified) further teaches wherein a majority of said opsonized plasmonic sub-micron nanoparticles further comprise opsonized plasmonic sub-micron nanoparticles selected from the group consisting of nanoplates, solid nanoshells, hollow nanoshells, nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanobipyramids, nanoprisms, nanostars and combinations thereof [see, e.g., ¶[0093[ (“In non-limiting examples, the nanoparticles are shaped as spheres, ovals, cylinders, squares, rectangles, rods, stars, tubes, pyramids, stars, prisms, triangles, branches, plates or comprised of a planar surface. In non-limiting examples, the plasmonic particles comprise nanoplates, solid nanoshells, hollow nanoshells nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanoprisms, or a combination thereof”)].
16. Regarding claim 9, the combination of Harris, Gendelman, and Peer, as evidenced by Ul-Islam, teaches all of the limitations of claim 3 for the reasons set forth in detail (above) in the Office Action.
Harris (as modified) further teaches wherein a majority of said composite opsonized plasmonic sub-micron nanoparticles further comprise composite opsonized plasmonic sub-micron nanoparticles selected from the group consisting of nanoplates, solid nanoshells, hollow nanoshells, nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanobipyramids, nanoprisms, nanostars and combinations thereof [see, e.g., ¶[0093[ (“In non-limiting examples, the nanoparticles are shaped as spheres, ovals, cylinders, squares, rectangles, rods, stars, tubes, pyramids, stars, prisms, triangles, branches, plates or comprised of a planar surface. In non-limiting examples, the plasmonic particles comprise nanoplates, solid nanoshells, hollow nanoshells nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanoprisms, or a combination thereof”)].
17. Regarding claim 10, the combination of Harris, Gendelman, and Peer, as evidenced by Ul-Islam, teaches all of the limitations of claim 4 for the reasons set forth in detail (above) in the Office Action.
Harris (as modified) further teaches wherein a majority of said composite opsonized plasmonic sub-micron nanoparticles further comprise composite opsonized plasmonic sub-micron nanoparticles selected from the group consisting of nanoplates, solid nanoshells, hollow nanoshells, nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanobipyramids, nanoprisms, nanostars and combinations thereof [see, e.g., ¶[0093[ (“In non-limiting examples, the nanoparticles are shaped as spheres, ovals, cylinders, squares, rectangles, rods, stars, tubes, pyramids, stars, prisms, triangles, branches, plates or comprised of a planar surface. In non-limiting examples, the plasmonic particles comprise nanoplates, solid nanoshells, hollow nanoshells nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanoprisms, or a combination thereof”)].
18. Regarding claim 12, the combination of Harris, Gendelman, and Peer, as evidenced by Ul-Islam, teaches all of the limitations of claim 6 for the reasons set forth in detail (above) in the Office Action.
Harris (as modified) further teaches wherein a majority of said opsonized plasmonic sub- micron nanoparticles further comprise opsonized plasmonic sub-micron nanoparticles selected from the group consisting of nanoplates, solid nanoshells, hollow nanoshells, nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanobipyramids, nanoprisms, nanostars and combinations thereof [see, e.g., ¶[0093[ (“In non-limiting examples, the nanoparticles are shaped as spheres, ovals, cylinders, squares, rectangles, rods, stars, tubes, pyramids, stars, prisms, triangles, branches, plates or comprised of a planar surface. In non-limiting examples, the plasmonic particles comprise nanoplates, solid nanoshells, hollow nanoshells nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanoprisms, or a combination thereof”)].
19. Regarding claim 13, the combination of Harris, Gendelman, and Peer, as evidenced by Ul-Islam, teaches all of the limitations of claim 7 for the reasons set forth in detail (above) in the Office Action.
Harris (as modified) further teaches wherein a majority of said opsonized plasmonic sub- micron nanoparticles further comprise opsonized plasmonic sub-micron nanoparticles selected from the group consisting of nanoplates, solid nanoshells, hollow nanoshells, nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanobipyramids, nanoprisms, nanostars and combinations thereof [see, e.g., ¶[0093[ (“In non-limiting examples, the nanoparticles are shaped as spheres, ovals, cylinders, squares, rectangles, rods, stars, tubes, pyramids, stars, prisms, triangles, branches, plates or comprised of a planar surface. In non-limiting examples, the plasmonic particles comprise nanoplates, solid nanoshells, hollow nanoshells nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanoprisms, or a combination thereof”)].
Response to Arguments
20. As noted above, the 05/06/26 Amendment has overcome the claim objections previously set forth in the 02/05/26 Action, while the cancellation of claims 5 & 11 has rendered the prior rejection of these claims under § 103 moot.
21. The prior rejection of claims 1, 3, 4, 6-10, 12, & 13 under § 103 has been updated to address the new limitations, and maintained.
22. The limitation at issue, which is the focus of Applicant’s arguments, concerns the “size” of the nanoparticles. Claim 1, for example, recites:
… wherein (1) (a) a longest dimension of at least about 80% of said opsonized plasmonic sub-micron nanoparticles is less than about 800 nm; and (b) the longest dimension of at least about 95% of said opsonized plasmonic sub-micron nanoparticles is greater than 100 nm.
Emphasis added.
Independent claims 3, 4, 6, & 7 each include similar limitations.
Harris teaches use of particles having “an optimal particle size of 30-800 nm (e.g., 100-800 nm)” [see Harris, ¶[0247]; see also ¶’s [0085], [0190], [0262]]. As such, it is the Examiner’s position that Harris can be fairly characterized as 100% of the particles having an optimal particle size that falls within the range of 30-800 nm.
As noted in the body of the rejections, those skilled in the art will readily appreciate that reference to the "size" of a nanoparticle is typically to the length of the largest straight dimension of the nanoparticle (e.g., the size of a perfectly spherical nanoparticle is its diameter). However, Harris does not explicitly define particle “size” as comprising a “longest dimension” of the particle. For this reason, Gendelman is relied upon as much for providing evidence on the record that reference to the "size" of a nanoparticle is typically to the length of the largest straight dimension of the nanoparticle [see ¶[0029] of Gendelman] [see also the “Citation of Pertinent Prior Art” below], as it is for the teaching that it was known to utilize nanoparticles having a longest dimension of about 50nm to about 800nm (a range that overlaps with Applicant’s claimed range) in the delivery of therapeutics (a teaching that is essentially cumulative to that of Harris). The formulated rejection is then based on the well-established principle concerning the obviousness of similar and overlapping ranges.
In the “Remarks,” Applicant provides no evidence concerning the criticality of the claimed range. Rather, Applicant argues against the propriety of the reliance on Gendelman in the rejection under § 103 as follows:
However, in contrast to the present invention, the nanoparticles of Gendelman are nanoparticles of "therapeutic agents...for the treatment of a viral infection." Gendelman, [0002]. Nothing in Gendelman teaches "opsonized plasmonic sub-micron nanoparticles" for "treating a skin condition", as claimed herein. The Office Action gives no specific reason to conclude that the size range of Gendelman's nanoparticles, which are for treating viral infections, that is, a purpose having nothing to do with the purpose of the present invention, has any bearing on the size ranges of the "opsonized plasmonic sub-micron nanoparticles" for "treating a skin condition" of claims 1, 3, 4, 6, and 7. Moreover, the present invention is for topical use, while the particles of Gendelman are meant to treat an infection with HIV, which is simply not a condition of the skin, but rather, a hematopoietic disease that infects CD4 T cells within the HIV patient. Therefore, while Gendelman teaches a nanoparticle size range, that range does not disclose, teach, suggest, or motivate the size ranges recited in claims 1, 3, 4, 6, and 7. Peer and Ul-Islam do not supply what Harris and Gendelman fail to disclose, teach, suggest, or motivate. As such, claims 1, 3, 4, 6, and 7 are non-obvious over Harris, Gandelman, Peer, and Ul-Islam, alone or in combination, for at least this reason. Therefore, the prima facie case of obviousness fails.
05/05/26 Amendment, pgs. 9-10.
Applicant’s arguments have been fully considered, but they are not persuasive.
As an initial matter, Harris, not Gendelman, is relied upon for the teaching of opsonized plasmonic sub-micron nanoparticles for treating a skin condition. Harris again already teaches use of particles having “an optimal particle size of 30-800 nm (e.g., 100-800 nm)” [see Harris, ¶[0247]; see also ¶’s [0085], [0190], [0262]].
Gendelman teaches a range that overlaps with Applicant’s claimed range, i.e., 100% of the nanoparticles in Gendelman have a longest dimension that falls within 50-800 nm, while 95% of Applicant’s nanoparticles have a size greater than 100 nm and at least about 80% have a size of less than 800 nm.
Moreover, and contrary to Applicant’s assertion, the teachings of Gendelman are broader than merely treating “an infection with HIV.” For example, Gendelman clearly teaches that conditions of the skin (e.g., herpes simplex) can also be treated topically with the nanoparticle formulations disclosed therein, along with microbial infections:
[0015] …While the prodrugs and nanoparticles of the instant invention are generally described as anti-HIV agents, the prodrugs and nanoformulations of the instant invention are also effective against other viral infections including, without limitation: hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), and Ebola virus. The prodrugs and nanoformulations of the instant invention are also effective against other microbial infections such as Mycobacterium tuberculosis.
Gendelman, ¶[0015], emphasis added.
***
[0061] Nanoparticles of the instant invention may be administered by any method. For example, the nanoparticles of the instant invention can be administered, without limitation parenterally, subcutaneously, orally, topically, pulmonarily, rectally, vaginally, intravenously, intraperitoneally, intrathecally, intracerbrally, epidurally, intramuscularly, intradermally, or intracarotidly… Dosage forms for topical administration include, without limitation, creams, gels, ointments, salves, patches and transdermal delivery systems.
Gendelman, ¶[0061], emphasis added.
As such, it is the Examiner’s position that Gendelman (and the nanoparticle sizes taught therein) would have logically commended itself to the inventor’s attention in considering nanoparticle sizes used for topical treatment of a skin condition. For each of the foregoing reasons, Applicant has failed to adequately rebut the prima facie case of obviousness, and the rejections under § 103 have been maintained.
Citation of Pertinent Prior Art
23. The following prior art is made of record for the purposes of further establishing the art-recognized definition of the "size" of a nanoparticle:
U.S. 2011/0097410 to Berney - ¶[0032] (“By nanoparticle "size" or "size range" we mean that the average longest dimension of the nanoparticles in a collection or preparation of nanoparticles falls within the range. Those of skill, in the art will recognize that the "longest dimension" of a particle will depend on the shape of the particle. For example, for particles that are roughly or substantially spheroid, the longest dimension will be a diameter of the particle. For other particles (e.g. crystals that may have, for example, angular shapes) the longest dimension may be e.g. a diagonal, a side, etc.”);
U.S. 2011/0044911 to Akhtari et al. - ¶[0015] (“Reference to the "size" of a nanoparticle is a reference to the length of the largest straight dimension of the nanoparticle. For example, the size of a perfectly spherical nanoparticle is its diameter”); and
U.S. 2009/0175915 to Maitra et al. - ¶[0026] (“Reference to the size of a pigment or nanoparticle means the length of the largest straight dimension of the pigment or nanoparticle. By way of example, the size of a spherical pigment is its diameter, and the size of a spherical nanoparticle is its diameter”).
Conclusion
24. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee 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 date of this final action.
25. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Bradford C. Blaise whose telephone number is (571) 272-5617. The Examiner can normally be reached on Monday - Friday, 8:30 AM - 4:30 PM MST.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Joanne M. Rodden, can be reached at telephone number 303-297-4276. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRADFORD C. BLAISE/Primary Examiner, Art Unit 3794
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