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 .
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Saudi Arabia on 11/16/23. It is noted, however, that applicant has not filed a certified copy of the SA 123450838 application as required by 37 CFR 1.55.
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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. Specifically, it is noted that the claim fails to include all the limitations of the claim upon which it depends since it would appear to limit the first layer to only consist of the titanium dioxide nanotubes without any ciprofloxacin. However, independent claim 1 requires the titanium dioxide nanotubes to contain ciprofloxacin and so it must also be required in any subsequent claims.
One way to correct the issue would be to amend claim 2 to refer to “the titanium dioxide nanotubes containing ciprofloxacin aligned adjacently” or some other similar amendment since this would include all the earlier limitations with respect to the claimed first layer.
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.
Please note, for purposes of claim interpretation the examiner will be treating the claim as referring to the titanium dioxide nanotubes containing ciprofloxacin since this appears in keeping with applicants’ likely intent.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-7 and 9-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over US Pub. No. 2013/0196128 to Friedrich et al., (hereinafter referred to as “FRIEDRICH”) in view of “Ciprofloxacin-Loaded Titanium Nanotubes Coated with Chitosan: A Promising Formulation with Sustained Release and Enhanced Antibacterial Properties” by Asadi et al., Pharmaceutics 14, 1359 (published 6/27/22) (hereinafter referred to as “ASADI”) and US Pub. No. 2026/0048259 to Smyth et al., (hereinafter referred to as “SMYTH”).
Regarding claim 1, FRIEDRICH teaches a biomedical implant system (see generally FRIEDRICH at Abstract and ¶7, ¶83-¶85 teaching medical implants made based on the teachings), comprising:
a substrate (see FRIEDRICH at ¶66 and ¶67 teaching the use of surgical grade titanium and titanium alloys);
a coating present on a surface of the substrate (see FRIEDRICH at ¶65-¶66 teaching the formation of an anodized coating on the surface of the titanium substrate),
wherein the coating comprises a first layer comprising titanium dioxide nanotubes (see FRIEDRICH at ¶66 and ¶68),
wherein the titanium dioxide nanotubes extend perpendicularly from a surface of the substrate (see FRIEDRICH at ¶75 teaching the nanotubes being formed via anodization which includes titania, i.e. titanium dioxide, nanotubes on the surface of the substrate after anodization),
wherein the titanium dioxide nanotubes contain ciprofloxacin (see FRIEDRICH at ¶88-¶91 teaching the nanotubes being used to provide drugs; see also FRIEDRICH at ¶94-¶95 teaching various antimicrobial agents including ciprofloxacin as claimed),
While FRIEDRICH teaches a titanium based implant having titania nanotubes which are then filled with a therapeutic agent as needed (see teachings of FRIEDRICH cited above), FRIEDRICH fails to explicitly teach the coating also comprising a second layer comprising a polyvinylidene fluoride polymer (“PVDF”) wherein the titanium dioxide nanotubes are capped on the outer end with the PVDF polymer.
However, ASADI teaches a titanium substrate with an anodically formed nanotubes which are loaded with a drug, specifically ciprofloxacin, and then coated with a polymer layer so as to form a second layer which caps the outer ends of the nanotubes as claimed (see ASADI at Abstract; see also ASADI at Scheme 1 on page 3 and also the first paragraph on page 3). Moreover, ASADI teaches the benefit of the polymer layer being that it reduces the rate of drug elution, i.e. extends the period of time over which the drug is released (see ASADI at section 3.6 on pages 13-14). Furthermore, ASADI teaches that the thickness of the polymer coating can be used to tune the drug elution rate since a reduced diffusion rate is caused by a thicker polymer layer (see ASADI at section 3.6 on pages 13-14).
While ASADI teaches the use of a chitosan polymer layer to block the outer ends (see ASADI at Abstract), SMYTH teaches an implant apparatus having a drug containing portion that uses a porous polymeric barrier made of PVDF to slowly diffuse the therapeutic (see SMYTH at Abstract; see also SMYTH at ¶164-¶167 teaching the barrier being porous and made of PVDF so as to allow a therapeutic agent to diffuse through the barrier at a desired rate; and also ¶160 teaching the therapeutic substance including amongst other things drugs).
As such, one of ordinary skill in the art would have recognized that a polymeric barrier could be added to the open ends of the titania nanotubes in order to length and control the diffusion of the therapeutic out of the nanotube to be at a desired/optimum rate. Moreover, one of ordinary skill in the art would have been motivated to have done so as to allow for a sustained release profile and would have recognized that any none diffusion barrier polymer could be used including PVDF.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added a polymeric coating to biomedical implant of FRIEDRICH as taught by ASADI as a means of controlling the rate of diffusion and furthermore to have used a PVDF polymeric coating since PVDF, as taught by SMYTH, is a known drug diffusion barrier material.
Regarding claim 2, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein the first layer consists of the titanium dioxide nanotubes containing ciprofloxacin aligned adjacently (see FRIEDRICH at Fig. 1 and Fig. 4A and 4B; see also ASADI at Scheme 1 on page 3 showing what titania nanotubes formed via anodization form orthogonally from the substrate surface).
Regarding claim 3, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein a first end of the titanium dioxide nanotubes is attached to the surface of the substrate and a second end of the titanium dioxide nanotubes is open-faced and exposed to the PVDF polymer (see FRIEDRICH at Fig. 1 and Fig. 4A and 4B; see also ASADI at Scheme 1 on page 3 showing what titania nanotubes formed via anodization having the first end and second end as claimed).
Regarding claim 4, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein the titanium dioxide nanotubes have an inside diameter of 20 nm to 60 nm (see FRIEDRICH at ¶77 teaching the inner diameter of the nanotubes ranging from 3 nm to 300, preferably 30-80 nm).
Regarding claim 5, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein the titanium dioxide nanotubes have a length of 1 µm to 5 µm (see FRIEDRICH at ¶77 teaching the length ranging from 1 µm to 100 µm).
Regarding claim 6, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein the titanium dioxide nanotubes have a wall thickness of 0.2 nm to 5 nm (see FRIEDRICH at ¶77 teaching the wall thickness ranging from 3 nm to 300 nm).
Regarding claim 7, FRIEDRICH as modified by ASADI and SMYTH fails to explicitly teaches the biomedical implant system wherein the second layer has a thickness of 5 µm to 10 µm. While ASADI teaches the thickness of the polymer layer ranging up to 4.2 µm (see ASADI at Table 4), ASADI also teaches that the thickness of the polymer layer can be controlled to provide a diffusion rate as desired (see ASADI at paragraph extending over pages 13-14).
One of ordinary skill in the art would have recognized that the thickness of the second layer could be optimized, i.e. increased so as to decrease the diffusion rate or decreased so as to increase the diffusion rate, or tuned so as to obtain the necessary diffusion rate.
Regarding claim 9, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein the substrate is a commercially pure titanium sample (see FRIEDRICH at ¶66 teaching the substrate being pure titanium sheets).
Regarding claim 10-13, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein the system is made by an anodization process as claimed (see FRIEDRICH at ¶66-¶81 and teachings of FRIEDRICH, ASADI and SMYTH as set forth above with respect to the rejection of claim 1 teaching all of the structural features of the claimed biomedical implant system).
Furthermore, since the specifics of each of these claims are directed towards the processes used in forming the biomedical implant system, it is explicitly noted that all that is required for the prior art to read on these claims is the structure implied by the limitations. For the reasons as set forth above, the prior art of record as combined teaches all of the structure implied by the process steps.
Regarding claim 14, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein the biomedical implant system comprises titanium, oxygen, carbon, nitrogen, and fluorine (see rejection of claim 1 above as to the implant containing titania, i.e. TiO2, in the first layer and PVDF, i.e. –(C2H2F2)–, and Ciprofloxacin, i.e. C17H18FN3O3, so as to comprise Ti, O, C, N, and F as claimed.
Regarding claim 15, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein 70 to 95 percent of the titanium dioxide in the titanium dioxide nanotubes have an anatase phase crystallinity (see FRIEDRICH at ¶81 teaching a similar post anodization annealing step, i.e. 400-500 °C for 1-5 hours, to turn the titanium nanotubes to anatase which would result in the amount as claimed).
Regarding claims 16-19, these claims each recite various properties of the final biomedical implant system having the coating with the first and second layers as claimed in independent claim 1. As such, since FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system of claim 1 (see rejection of claim 1 above), these property limitations would also be met by the prior art as modified because the properties would directly follow from the structure.
Regarding claim 20, FRIEDRICH as modified by ASADI and SMYTH teaches the biomedical implant system wherein the Ciprofloxacin is released through the PVDF polymer over time (see rejection of claim 1 above showing the PVDF polymer being a porous diffusion barrier that would allow for the release over time as claimed).
Allowable Subject Matter
Claim 8 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: the prior art of record fails to teach the second layer being as claimed with a polymer mixture of PVDF and polylactic acid (“PLA”) with a mass ratio, thickness and coverage of the titanium dioxide nanotubes as claimed.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
“Titania Nanotube Arrays for Local Drug Delivery: Recent Advances and Perspectives” by Losic et al., Expert Opin. Drug Deliv., 12:1, pages 103-127 (2015)
“Drug Release Characteristics of Quercetin-Loaded TiO2 Nanotubes Coated with Chitosan” by Mohan et al., Int. J. Biol. Macromol. 93, pages 1633-1638 (2016)
“TiO2 Nanotube Arrays Deposited on Ti Substrate by Anodic Oxidation and Their Potential as a Long-Term Drug Delivery System for Anitmicrobial Agents” by Moseke et al., Appl. Surf. Sci. 258, pages 5399-5404 (2012)
“Biocompatible Polymer Coating of Titania Nanotube Arrays for Improved Drug Elution and Osteoblast Adhesion” by Gulati et al., Acta Biomater. 8, pages 449-456 (2012)
“Controlled and Localized Drug Delivery Using Titania Nanotubes” by Baranwal et al., Mater. Today Commun. 32, 103843 (2022)
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bryan D. Ripa whose telephone number is (571)270-7875. The examiner can normally be reached Mon-Fri 8:00AM-4:00PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Lin can be reached at (571) 272-8902. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRYAN D. RIPA/Primary Patent Examiner, Art Unit 1794
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