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 .
DETAILED ACTION
In view of the Appeal Brief filed on January 22, 2026 and the discussion during the Appeal Conference, PROSECUTION IS HEREBY REOPENED. New grounds of rejection are set forth below.
To avoid abandonment of the application, appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
Claims 1, 6, 7, 37, 38, 43-46, 48 and 49 are pending.
Claims 2-5, 8-36, 39-42 and 47 are cancelled.
Claims 1, 6, 7, 37, 38, 43-46, 48 and 49 as filed on May 20, 2025 are under consideration.
Withdrawn Objections / Rejections
In view of the discussion during the Appeal Conference, all previous claim rejections under 35 USC 112(b) are withdrawn and all previous claim rejections under 35 USC 103 over Mendelsohn in view of Millotti are withdrawn.
Appellant’s arguments have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
New Grounds of Rejection: 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, 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, 6, 7, 37, 38, 43-46, 48 and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Mendelsohn et al. (US 2017/0274089, published September 28, 2017, of record).
Mendelsohn teaches (provides) an implantable drug delivery system comprising (claims 23, 1):
a capsule suitable for implantation,
a reservoir encapsulated by the capsule, wherein the reservoir contains a therapeutic agent comprising exenatide (claims 2-5; paragraphs [0041], [0080]) and a stabilizing polymer having a diameter of at least 3 nm (insoluble) (claims 6-20; paragraph [0093]), wherein the pH is about 3 to 7, about 4 to 6 (claims 21, 22; paragraphs [0062], [0118]), as required by instant claims 6, 7, 43, 44, 48, 49,
a membrane in contact with the reservoir allowing diffusion of the therapeutic agent out of the reservoir, the membrane comprising titania nanotubes (nanoporous, plurality of pores) on a titanium substrate (paragraphs [0012]-[0013], [0088]-[0089], [0091]-[0092]).
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). See MPEP 2144.05. The stabilizing polymer is a buffering agent that can be any suitable material inclusive of a hydrogel (insoluble); the polymer may comprise monomers inclusive of acrylates or/and methacrylates (paragraphs [0040], [0021]; also [0043], [0086]), as required by instant claim 38. The polymeric buffering agent refers to a polymer having suitable ionizable groups such as acid or base functional groups to buffer a mixture (ion exchange resin) (paragraphs [0021], [0040]), as required by instant claim 45. The therapeutic agent within the reservoir can be in any suitable form inclusive of liquid (fluid formulation) (paragraph [0085]). The rate of release of the therapeutic agent can be any suitable rate of release (paragraph [0092]).
Mendelsohn exemplifies an embodiment in Example 15 wherein PAMAM-COOH was added to an exenatide solution (providing a fluid formulation of the therapeutic agent) to a final pH between 3 and 4 (selecting the pH between about 4.0 to about 7.0) (paragraph [0157]); reservoirs (providing the device) were filled with the solution (introducing the formulation into the reservoir of the capsule) (paragraph [0156], also all citations supra drawn to the details of the implantable drug delivery system, in particular claim 23 and paragraphs [0088]-[0089], [0091]-[0092] of Mendelsohn).
Mendelsohn further teaches exenatide is sensitive to oxidation and degradation at pH levels above 6 (paragraph [0118]). The preferred pH depends on the therapeutic agent in the reservoir (paragraphs [0009], [0040]).
Although Mendelsohn is in possession of / has already provided a drug delivery system as instantly claimed, Mendelsohn does not specifically teach the “provision” as a method for controlling the rate of release of a therapeutic or/and that the rate of release is dependent upon the pH of the fluid formulation as required by claims 1, 37, 46. However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide exenatide containing implantable drug delivery systems according to Mendelsohn having a reservoir pH of about 3 to 7, or about 4 to 6 with a reservoir pH level below 6 because exenatide is sensitive to oxidation and degradation at pH levels above 6 according to Mendelsohn (paragraph [0118]). There would be a reasonable expectation of success because Mendelsohn exemplifies an embodiment of exenatide containing system having a pH between 3 and 4. Regarding the provision as a method of controlling the rate of release, because Mendelsohn renders obvious the “selection” of the pH as instantly claimed, said selection to avoid oxidation and degradation of exenatide is necessarily also a method of controlling the rate of release and will necessarily achieve a desired rate of release. "The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Claims 1, 6, 7, 37, 38, 43-46, 48 and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Mendelsohn et al. (US 2017/0274089, published September 28, 2017, of record) in view of Ameri et al. (US 2009/0136554, published May 28, 2009) and Tsuru et al. “Titania membranes for liquid phase separation: effect of surface charge on flux,” Separation and Purification Technology 25:307-314, 2001, of record.
Mendelsohn is applied herewith under a different interpretation of the “selection” limitation in the interest of compact prosecution
Mendelsohn teaches (provides) an implantable drug delivery system comprising (claims 23, 1):
a capsule suitable for implantation,
a reservoir encapsulated by the capsule, wherein the reservoir contains a therapeutic agent comprising exenatide (claims 2-5; paragraphs [0041], [0080]) and a stabilizing polymer having a diameter of at least 3 nm (insoluble) (claims 6-20; paragraph [0093]), wherein the pH is about 3 to 7, about 4 to 6 (claims 21, 22; paragraphs [0062], [0118]), as required by instant claims 6, 7, 43, 44, 48, 49,
a membrane in contact with the reservoir allowing diffusion of the therapeutic agent out of the reservoir, the membrane comprising titania nanotubes (nanoporous, plurality of pores) on a titanium substrate (paragraphs [0012]-[0013], [0088]-[0089], [0091]-[0092]).
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). See MPEP 2144.05. The stabilizing polymer is a buffering agent that can be any suitable material inclusive of a hydrogel (insoluble); the polymer may comprise monomers inclusive of acrylates or/and methacrylates (paragraphs [0040], [0021]; also [0043], [0086]), as required by instant claim 38. The polymeric buffering agent refers to a polymer having suitable ionizable groups such as acid or base functional groups to buffer a mixture (ion exchange resin) (paragraphs [0021], [0040]), as required by instant claim 45. The therapeutic agent within the reservoir can be in any suitable form inclusive of liquid (fluid formulation) (paragraph [0085]). The rate of release of the therapeutic agent can be any suitable rate of release (paragraph [0092]).
Mendelsohn exemplifies an embodiment in Example 15 wherein PAMAM-COOH was added to an exenatide solution (providing a fluid formulation of the therapeutic agent) to a final pH between 3 and 4 (selecting the pH between about 4.0 to about 7.0) (paragraph [0157]); reservoirs (providing the device) were filled with the solution (introducing the formulation into the reservoir of the capsule) (paragraph [0156], also all citations supra drawn to the details of the implantable drug delivery system, in particular claim 23 and paragraphs [0088]-[0089], [0091]-[0092] of Mendelsohn).
Mendelsohn further teaches exenatide is sensitive to oxidation and degradation at pH levels above 6 (paragraph [0118]). The preferred pH depends on the therapeutic agent in the reservoir (paragraphs [0009], [0040]).
Mendelsohn, as a whole, is drawn to sustained drug delivery; as an example, exenatide is used for the treatment of diabetes (paragraph [0002]).
Although Mendelsohn is in possession of / has already provided a drug delivery system as instantly claimed, Mendelsohn does not explicitly teach the “provision” as a method for controlling the rate of release of a therapeutic or/and that the rate of release is dependent upon the pH of the fluid formulation as required by claims 1, 37, 46.
These deficiencies are made up for in the teachings of Ameri and Tsuru.
Ameri teaches transdermal sustained release drug delivery of exenatide (title; abstract; claims, e.g., claim 1). The charge profile of extendin-4 (exenatide) is shown in FIG. 12:
PNG
media_image1.png
400
610
media_image1.png
Greyscale
At pH 4.4, extendin-4 (exenatide) presents a zero net electric charge (paragraphs [0104], [0078]).
Tsuru teaches the effect of surface charge on flux through titania membranes (title; abstract). The surface of metal oxides has no charge at the iso-electric point (IEP); the charge changes from positive to negative, depending upon the pH of solution (page 308, paragraph bridging columns; Figure 3). Permeate fluxes maximize near the IEP (abstract; Figure 7; conclusion). For macromolecules such as proteins, electric force between a membrane and the solutes whose sign of charge is opposite to that of the membrane causes fouling resulting in a decrease in flux through the membrane (page 308, rhc, 1st full paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the exenatide within the reservoir of the exenatide containing implantable drug delivery systems according to Mendelsohn has a pH dependent charge because Ameri illustrates such.
It would have been obvious to one of ordinary skill in art before the effective filing date of the claimed invention that the release (flux) of the exenatide through the titania nanotube membrane of the exenatide containing implantable drug delivery systems according to Mendelsohn is affected by the pH because Tsuru teaches the electric force between a titania membrane and the solutes whose sign of charge is opposite to that of the membrane causes fouling resulting in a decrease in flux through the membrane and Tsuru teaches the flux of charged ions through titania membranes maximizes near the iso-electric point of the titania. Therefore, the provision of exenatide containing implantable drug delivery systems according to Mendelsohn having a specified reservoir pH selected within the range of about 3 to 7, or about 4 to 6 as taught by Mendelsohn controls the rate of release of exenatide through a titania membrane and the combined teachings of Mendelsohn, Ameri and Tsuru render obvious the selection / optimization of the reservoir pH of the exenatide containing implantable drug delivery systems according to Mendelsohn in order to achieve a desired / optimized rate of release.
Response to Arguments
Appellant’s arguments filed have been fully considered and are addressed herein to the extent they may pertain to the new grounds of rejection applied infra over Mendelsohn.
Appellant’s citation to the Declaration at pages 19-24 of the Remarks remains unpersuasive for reason of record. See page 8 of the Final Rejection mailed May 30, 2025.
Appellant’s argument at page 20 of the Remarks that Mendelsohn discusses pH only in relation to stability (not release rate) is not found persuasive. As set forth in the new grounds of rejection over Mendelsohn applied infra, Mendelsohn discusses pH and expressly motivates the ordinary artisan to “select” pH values below 6 because exenatide is sensitive to oxidation and degradation at pH values above 6. Once this “selection” has been made, the selection is necessarily achieves “a desired rate of release”.
Appellant’s argument at page 21 of the Remarks that the present case is different than Millotti is unpersuasive because paragraph [0065] of the instant specification expressly states that the rate of release is faster when “both the exenatide and the interior surface of the nanotubes are predominantly negatively charged”. This finding of Appellant is expected in view of Millotti.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISSA PROSSER whose telephone number is (571)272-5164. The examiner can normally be reached M - Th, 10 am - 6 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, DAVID BLANCHARD can be reached on (571)272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALISSA PROSSER/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
Prosecution Insights