DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 31, 2026 has been entered.
Status of Claims
Claims 1, 3-8, 19-20 and 22 are pending. Claims 2, 9-18 and 21 are canceled. Claims 1 and 19-20 are amended.
Claims 1, 3-8, 19-20 and 22 are examined based on their merits.
Previous Rejections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Rejections Withdrawn
Claim Rejections - 35 USC § 103
Upon further consideration the rejection of claims 1 and 4-8 under 35 U.S.C. 103 as being unpatentable over Nuxoll et al. WO 2018/005541 (1/4/2018)(11/11/2021 IDS) in view of Vitaliano et al. US 2012/0263793 (10/18/2012) and Losick et al. US 2013/071439 (3/21/2013)(11/11/2021 IDS) is withdrawn.
Upon further consideration the rejection of claim 3 under 35 U.S.C. 103 as being unpatentable over Nuxoll et al. WO 2018/005541 (1/4/2018)(11/11/2021 IDS) in view of Vitaliano et al. US 2012/0263793 (10/18/2012) and Losick et al. US 2013/071439 (3/21/2013)(11/11/2021 IDS) as applied to claims 1 and 4-8 and further in view of Wan et al. US 2013/0202672 (8/8/2013) is withdrawn.
Upon further consideration the rejection of claims 19-20 and 22 under 35 U.S.C. 103 as being unpatentable over Nuxoll et al. WO 2018/005541 (1/4/2018)(11/11/2021 IDS) in view of Vitaliano et al. US 2012/0263793 (10/18/2012) and Losick et al. US 2013/071439 (3/21/2013)(11/11/2021 IDS) as applied to claims 1 and 4-8 and further in view of Bornstein CA 2670711 (6/19/2008) and JP 2008/162933 (7/17/2008)(“JP”) is withdrawn.
New Rejections
Claim Rejections - 35 USC §112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 4 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the applicant regards as the invention.
Claim 4 is rejected under 35 USC 112(b) for reciting the limitation “wherein the one or more D-amino acids comprise a mixture of D-tyrosine, D-tryptophan and D-phenylalanine”. There is insufficient antecedent basis for this limitation in claim 4 because claim 1 recites “one or more basic D-amino acids” in line 6. However, none of D-tyrosine, D-tryptophan and D-phenylalanine are basic D-amino acids.
Additionally, the phrase is vague and confusing and it is not clear what one or more D-amino acids are being referred to because claim 1 recites “one or more basic D-amino acids”. However, D-tyrosine, D-tryptophan and D-phenylalanine are not basic amino acids.
This phrase is not defined nor explained in the specification and cannot be determined by reference to any other claims. As a result, one of ordinary skill in the art would not be reasonably apprised of how to determine what this phrase means.
For the purposes of this office action, claim 4 will be interpreted as if it is referring to the one or more basic D-amino acids in claim 1 (even though none of D-tyrosine, D-tryptophan and D-phenylalanine are basic D-amino acids).
Claim Rejections - 35 USC §112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 22 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 22 is rejected as being indefinite for failing to further limit in the recitation of “wherein the one or more D-amino acids are basic amino D-amino acids and have a concentration of about 200 mM to about 400 mM” wherein claim 22 depends from claim 1.
Claim 1 already recites “wherein the one or more D-amino acids are basic amino D-amino acids and have a concentration of about 200 mM to about 400 mM”. Since the one or more D-amino acids are already required to be basic D-amino acids and have a concentration of about 200 mM to about 400 mM in claim 1, claim 22 does not further limit claim 1. This is a failure to further limit the claim from which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-8, 19-20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Vitaliano et al. US 2012/0263793 (10/18/2012) in view of Wan et al. US 2013/0202672 (8/8/2013), Nuxoll et al. WO 2018/005541 (1/4/2018)(11/11/2021 IDS), Losick et al. US 2013/071439 (3/21/2013)(11/11/2021 IDS), Bornstein CA 2670711 (6/19/2008) and JP 2008162933 (7/17/2008)(“JP”).
Vitaliano relates to plasmonics and teaches a method of using nanoscale metal surface elements that when appropriate forms of energies are applied to the metal elements emit a type of surface-plasmon-enhanced electromagnetic radiation and energy. (See Abstract). Vitaliano teaches lasers being used to remediate biofilms. (See [0524]. Vitaliano teaches that biofilms that form in the human body are more than 10,000 times more resistant to antibiotics and immune systems than free-floating bacteria and in humans and animals biofilms are responsible for 80% of all infections.
Vitaliano teaches that lasers are used in an embodiment to remedy in vivo biofilms in humans and animals. (See [0525]). Lasers are known to cause bacterial mortality, and in an embodiment the laser emits a highly targeted coherent light energy that disrupts biofilms. See [0526 and 0528]). Vitaliano teaches that in an embodiment, gold nanorods are exposed to resonant illumination and transformed. (See [0149]). Gold nanorods are called for in instant claims 6 and 21 and they are plasmonic particles as called for in claims 1 and 20. Vitaliano teaches the application of light energy from a light source that excites the plasmonic particles to cause a disruption of biofilm formation as called for in instant claim 1. Vitaliano also teaches the use of lasers to emit light energy to disrupt biofilms as called for in claim 7.
The energy applied to the nanocomposite is a laser supplying light as called for in instant claim 7. Vitaliano teaches that the excitation with lasers cause the gold nanoparticles to locally heat the targeted area, as called for in instant claims 1 and 20. (See [0058]).
Vitaliano does not expressly teach a hydrogel comprising a glycol chitin-based hydrogel containing the non-magnetic nanoparticle or a medical implant with such a coating. Vitaliano also does not teach that amino acids are effective for the disruption of biofilms. These deficiencies are made up for with the teachings of Wan et al., Nuxoll, Losick et al., Bornstein and JP 2008162933.
Wan et al. (Wan) teaches fiber-assembled tissue constructs suitable for biological applications including tissue engineering. (See Abstract and [001]). Wan teaches that suitable fiber matrices can include chitin-based hydrogels and are known in the art. (See [0103]). A chitin-based hydrogel is called for in instant claim 3.
Nuxoll et al. (Nuxoll) discloses a hydrogel comprising a thermoresponsive polymer and a magnetic nanoparticle is used for the disruption of biofilm. Specifically, a magnetically-sensitive coating on the surface of an implantable device that comprises a polymer and magnetic particles embedded within the polymer and a coil element capable of generating an alternating magnetic field that can induce heating of the surface of the implantable device. (See Abstract).
The nanocomposite is a hydrogel as called for in instant claims 1 and 20-21. (See Abstract and [096], [099] and [0105]. The nanocomposite can comprise antibiotics as called for in instant claim 5. (See Example 5). Nuxoll teaches a medical implant that is coated with the nanocomposite hydrogel as called for in instant claim 8. (See Abstract).
Losick et al. (Losick) teaches that D-amino acids are effective for the disruption of biofilms. (See claims 1, 12 and 28). Losick teaches that mixtures including D-tyrosine, D-tryptophan and D-phenylalanine are useful amino acids at disrupting biofilms. (See [0007]). A mixture of D-tyrosine, D-tryptophan and D-phenylalanine is called for in instant claim 4. D amino-acids are called for in instant claims 20s. Losick teaches that the minimum concentration necessary to disrupt biofilms was around 1 mM for D-tryptophan and D-tyrosine needed at least 100 nM concentration to disrupt biofilms. (See [0217]). At least 1 mM overlaps with the concentration of about 200 nM to about 400 mM called for in instant claims 1 and 22.
JP teaches a water-soluble chitin is used as an active component for antifungal action. (See Abstract). JP teaches that the propagation of fungus can be prevented or suppressed by compounding the water-soluble chitin to an antifungal agent. (See Abstract). JP teaches a method of suppressing mold generation and common fungi. (See [0002-0003]). JP teaches that the chitin can suppress the formation of mold biofilms and fungal biofilms. (See [0013] and [0027]). It can be present in an amount of 0.01 to 100 %. (See [0014]).
JP teaches that glycol chitin is an example of the water-soluble chitin. (See [0050]). Glycol chitin is called for in instant claims 3 and 19-20. 0.01 to 100 % overlaps with the about 1-8 wt% called for in instant claim 19.
The teachings of Vitaliano, Nuxall and Losick are described supra. Claim 19 is directed to a product. It does not appear that the power level affects or changes the structure of the nanocomposite as claimed. Since the prior art teaches all of the elements of the structure of the nanocomposite as claimed and there is motivation to combine the teachings of the prior art to reach the claimed nanocomposite in claim 19 as described above, claim 19 is rendered obvious by the combined teachings of the prior art of Vitaliano in view of Wan, Nuxall and Losick. However, in the event that power is needed to render a particular structure of the nanocomposite, the power level is obvious for the reasons described below.
Bornstein teaches near-infrared optical energies to alter irradiated targets. (See Abstract). Bornstein teaches power densities that were empirically tested for various treatment of microbial species. Bornstein teaches that power densities empirically tested for various in vitro treatment of microbial species were from about 1 W/cm2. Thus Bornstein teaches a near-infrared laser having a power of about 1 W/cm2 as called for in instant claims 19-20.
Bornstein teaches that one of skill in the art will appreciate that the identification of particularly suitable laser power values (NIMELS dosimetery) may empirically done via routine experimentation. Thus, Bornstein teaches that the power levels and parameters as called for in instant claim 20 are no more than routine experimentation.
It would be prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the Vitaliano nanocomposite for disrupting biofilm formation to place the gold nanoparticles in a thermoresponsive hydrogel as taught by Nuxoll and have the thermoresponsive polymer be a glycol-chitin polymer based hydrogel in view of Wan’s teaching that a glycol chitin-based hydrogel is a suitable and well known fiber matrix for biological applications.
It would be prima facie obvious for one of ordinary skill in the art before the earliest effective filing date of the invention making the Vitaliano nanocomposite
to include a mixture of mixture of D-tyrosine, D-tryptophan and D-phenylalanine in the nanocomposite as taught by Losick in light of Losick’s teaching that this mixture of D-amino acids is effective at disrupting biofilms.
It would be prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the Vitaliano nanocomposite with gold nanorods and a mixture of D-tyrosine, D-tryptophan and D-phenylalanine present in at least 1 mM in order to have a mixture of D-amino acids that is effective at disrupting biofilms and to use a laser emitting near infrared light energy with a power density of about 1 W/cm2 and to routinely experiment to determine the ideal wavelength and amount of time to use the light laser as taught by in light of Vitaliano’s teaching that the use of lasers emitting light energy is effective to disrupt biofilms and gold nanorods are useful plasmonic particles for such a purpose.
It would be prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the Vitaliano in view of Nuxall and Losick nanocomposite with gold nanorods and a mixture of at least 1 mM D-tyrosine, D-tryptophan and D-phenylalanine to have 0.01 to 100% glycol chitosan polymer as taught by JP in order to have another active that prevents the formation of biofilms as taught by JP.
With respect to the property of viscosity at room temperature and a change in viscosity at physiological temperature, the references are silent regarding the viscosities. However, the prior art teaches the same components of a glycol chitin based hydrogel containing gold nanorods and antibiotics and a mixture of D-tyrosine, D-tryptophan and D-phenylalanine amino acids. It would appear that the composition of Vitaliano in view of Wan, Nuxoll, Losick, Bornstein and JP would necessarily possess a viscosity that is greater at the physiological temperature than the room temperature. Following the teachings of the prior art would necessarily cause the nanocomposite to have a first viscosity at room temperature and a greater viscosity when exposed to physiological temperature as evidenced by the specification at [0141-142].
Response to Arguments
Applicants’ remarks filed March 31, 2026 and the Affidavit of Anna Cristina Samia have been fully considered and are found to be partly persuasive and partly unpersuasive for the following reasons.
Applicants note the amendment to the claims and where support can be found.
Applicants argue that Nuxoll in view of Vitaliano and Losick does not render the claims obvious because the proposed modification of Nuxoll with Vitaliano and Losick would render Nuxoll unsatisfactory for its intended purpose, the proposed modification of Nuxoll with Vitaliano would change the principle of operation of Nuxoll and the skilled artisan would not have had a reasonable expectation of success.
Applicants note again that Nuxoll relies on magnetically induced hyperthermia, which produces a distributed heating effect across the implant. Nuxoll discloses a pre-coated implant surface designed for passive, post-implantation biofilm disruption via magnetic heating and the composition is static and designed to remain permanently on the implant.
Applicants argue that Nuxoll would be unsatisfactory for its intended purpose of long-term biofilm disruption because the Nuxoll hydrogel would be transformed into a thermoreversible nanocomposite which is not formulated for permanent adherence because it provides temporal control with transient localization and removal after treatment.
Nuxoll relies on magnetically induced hyperthermia, which produces a distributed heating effect across the implant. In contrast, the claimed nanocomposite utilizes gold nanorods to achieve localized, wavelength-specific photothermal heating under near infrared laser activation. This enables spatially confined energy delivery directly at the biofilm-implant interface, allowing for selective thermal ablation of bacterial biofilms while minimizing collateral damage to surrounding healthy tissues. Applicants additionally assert that gold nanorods are known to be sensitive to aggregation and environmental conditions, so the skilled artisan would have known that incorporating gold nanorods into a coating designed for indefinite in vivo residence. (as in Nuxoll) would have compromised their stability and functionality.
The skilled artisan would not have had a reasonable expectation of success in combining the D-amino acids of Losick with the particles of Vitaliano because individually the D-amino acids of Losick and the Vitaliano particles would not have been expected to achieve the claimed invention.
Applicants assert that the claimed thermoreversible nanocomposite exhibits unexpected, synergistic properties, including complete biofilm eradication and synergistic results whereas there is only partial activity with the components alone.
Applicants note the comparison of the presently claimed invention against the use of a magnetically induced hyperthermia treatment as taught by Nuxoll in Example 2. Examples 2 uses magnetically induced hyperthermia and shows the adverse effects on chicken meat used int eh testing with all three types of implant materials used, whereas Example 3 shows the use of non-magnetic plasmonic particles of the instant invention. Examples 3 shows the ability of the non-magnetic plasmonic particles to achieve selective thermal ablation of the biofilm-implant interface while minimizing damage to the surrounding health tissue. This demonstrates significant and surprising improvements in the removal of biofilms without significant damage to surrounding tissues and there is nothing in Nuxoll to suggest such an improvement.
Applicants point to the Affidavit of Anna Cristina Samia and her discussion of the experimental data that the invention exhibits significant synergistic properties including complete biofilm eradiation and the in vitro studies that only the combination of basic D-amino acids, gold nanorods and laser activation results in complete eradication of biofilms. Neither the amino acid alone nor laser activation of gold nanorods alone achieved full biofilm clearance, so there was only partial activity with the components alone. These results clearly exceed additive effects and the synergy is unexpected based on the prior art. Applicants assert that the unexpected synergy would be achieved through the full scope of the claims as now amended.
Applicant’s arguments have been fully considered and are found to be partly persuasive and partly unpersuasive.
Applicants’ argument that the proposed modification of Nuxoll with Vitaliano and Losick would render Nuxoll unsatisfactory for its intended purpose is found to be sufficiently persuasive and the rejection has been withdrawn above.
As described in the new rejection applied above, it would be prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the Vitaliano nanocomposite for disrupting biofilm formation to place the gold nanoparticles in a thermoresponsive hydrogel as taught by Nuxoll and have the thermoresponsive polymer be a glycol-chitin polymer based hydrogel in view of Wan’s teaching that a glycol chitin-based hydrogel is a suitable and well known fiber matrix for biological applications and to include a mixture of D-tyrosine, D-tryptophan and D-phenylalanine present in at least 1 mM in the nanocomposite as taught by Losick in light of Losick’s teaching that this mixture of D-amino acids are effective at disrupting biofilms. It would also be prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the Vitaliano nanocomposite with gold nanorods and a mixture of at least 1 mM D-tyrosine, D-tryptophan and D-phenylalanine to have 0.01 to 100% glycol chitosan polymer as taught by JP in order to have another active that prevents the formation of biofilms as taught by JP.
As seen in the new rejection applied above, the Vitaliano gold nanoparticles are combined with only the hydrogel containing the thermoresponsive polymer and an antibiotic of Nuxoll, so none of the rest of the Nuxoll device is being used in the above instant prior art rejection. The arguments against the Nuxoll device are therefore no longer applicable. For example, the Vitaliano in view of Wan, Nuxoll, Losick, Bornstein and JP nanocomposite does not rely on magnetic hyperthermia for bacteria eradication and it is also not designed for indefinite in vivo residence, so any issues regarding any potential aggregation of gold nanoparticles would not have concerned nor impeded an ordinarily skilled artisan in combining gold nanorods in a glycol-chitin hydrogel and adding basic D-amino acids.
Rather, there would have been a reasonable expectation of success in light of Losick’s teaching that this mixture of D-amino acids is highly effective at disrupting biofilms. There also would have been a reasonable expectation of success in combining gold nanorods and D-amino acids in 0.01 to 100% glycol chitosan polymer in light of JP’s teaching that 0.01 to 100% glycol chitosan polymer is an active that prevents the formation of biofilms.
Applicants assertion of unexpected results are not found to be persuasive because the claims are not commensurate in scope with the showing of unexpected results and the evidence that Applicants are citing to support their assertion of unexpected results. Example 3 shows only a formulation of glycol-chitin with basic D-amino acids D-tyrosine, D-tryptophan and D-phenylalanine and gold nanoparticles tested. Claim 1 covers any plasmonic particle when only gold nanoparticles were tested. Claim 1 covers many thermoresponsive polymers when only chitin was tested in Example 3. Respectfully, assertions of synergy are only relevant for those compositions which have been tested.
While claim 20 is close to being commensurate in scope with the experiments that exhibit the synergistic results, it is still not commensurate in scope because the D-amino acids claimed are basic amino acids. D-Arginine, D-Lysine and D-Histidine are basic amino acids, but these were not used in the experimental data. Rather, the amino acids D-methionine, D-tryptophan, D-tyrosine and D-phenylalanine were used in the experimental data as seen in Figure 11A-B and Figure 12A-B as described in paragraphs [0020-0021] of the instant specification.
All showings of secondary considerations of obviousness must be commensurate in scope with the claims. Unexpected results must be commensurate in scope with the claims which the evidence is offered to support. See In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 196 (CCPA 1980). See MPEP 716.02(d). The submission of objective evidence of patentability does not mandate a conclusion of patentability in and of itself. In re Chupp, 816 F.2d 643, 2 USPQ2d 1437 (Fed. Cir. 1987). Facts established by rebuttal evidence must be evaluated along with the facts on which the conclusion of a prima facie case was reached, not against the conclusion itself. In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990). MPEP 716.01(d).
The remainder of Applicants arguments are moot in view of the new rejection applied above.
Conclusion
No claims are allowed.
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SARAH CHICKOS
Examiner
Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
Prosecution Insights