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 .
Applicants’ arguments, filed 08/22/2025, have been fully considered. Rejections and/or objections not reiterated from previous office action are hereby withdrawn.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.
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.
1) Claims 9, 10 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (US2003/0118649 A1, publication date 06/26/2003).
Regarding instant claims 9 and 15, Gao discloses a biodegradable drug delivery device comprising a core with a bioactive agent, such as hormones (paragraph 103), a first layer disposed around (i.e., encapsulating) the core and a second layer disposed around the first layer (p. 20, claim 20). The device may also comprise a third membrane layer disposed around the second layer (para. 11, on page 2). Wherein, the first layer comprises a water soluble polymer and biodegradable polymer, and the second layer comprises a second bioactive (p. 20, claim 20), which may be “a different therapeutic agent [from the core], or none at all” (paragraph 11). Whereby, dissolving the water soluble polymer of the first layer renders it porous, resulting in the release of the first bioactive in the core (i.e., the medication layers dissolve as the membrane layers dissolve; p. 20 claim 20). Gao discloses that this “porous membrane then controls the subsequent release of drug contained inside the inner core, and sustained release is then achieved” (paragraph 10). In other words, Gao discloses the release rate may be controlled by the permeability of the membrane layers (paragraph 82) and that in certain embodiments the bioactive agent has a sustained release of at least two days or at least a month (i.e., predefined period of time; paragraph 19). Gao also teaches the number of times the outer, active containing, layer is dip-coated effects the dose and release properties of the active contained therein, and that the active containing layers may comprise a plurality of dip-coatings (i.e., comprises a plurality of medication layers; p. 20, Table 2 & para. 198). Finally, Gao discloses the device is implanted into a patient (abstract) by, for example, injection (i.e., subcutaneous injection, limitation of instant claim 15; paragraph 45).
Gao is not anticipatory because Gao does not disclose a second membrane layer encapsulating a plurality of second medication layers.
It would have been obvious for one of ordinary skill in the art, at the time of filling, to have simply duplicated the third membrane layer and the second layer which comprises a plurality of dip coating layers and either a bioactive or no bioactive at all. One would have been motivated to duplicate these layers to provide a device with additional and alternating sustained release layers. One would have had a reasonable expectation of success because each element would have merely performed the same function as it did separately. Please refer to MPEP 2143 and MPEP 2144.04VI B.
It also would have been obvious to one of ordinary skill in the art, at the time of filling, to have provided the second a layer with no active agent, i.e., placebo, because Gao discloses it as an option.
Therefore, it would have been obvious to one of ordinary skill in the art, at the time of filling, to have formulated a biodegradable drug delivery device (i.e., pellet) comprising a plurality of first and second bioactive layers (i.e., medication layer) interposed between a plurality of sustained release layers (i.e., first and second membrane layers), such that the first membrane layer encapsulates a plurality of first medication layers and a plurality of first medication layers encapsulates a second membrane layer and a second membrane layer encapsulates a plurality of second medication layers. Wherein the first membrane layer dissolves over a predefined period of time and the second medication layer is a placebo, insofar as it provides no bioactive agent at all.
Regarding instant claim 11, Gao discloses the bioactive may include hormones (paragraph 103). Given the disclosure of each component individually, it would have been prima facie obvious to a person having ordinary skill in the art at a time prior to the filing of the present patent application and following the teachings of Gao to have selected and combined known components for their established functions with predictable results. MPEP 2143 and 2144.06(I). Therefore it, would have been obvious for one of ordinary skill in the art, at the time of filling, to have selected a biodegradable hormone as the first bioactive.
Regarding instant claim 14, Gao disclose that in certain embodiments the polymer formulations (i.e., sustained release layers) biodegrade over one year (i.e., membrane layers dissolve over the predefined time period of 12 months; paragraph 55). Therefore, it would have been obvious to one of ordinary skill in the art, at the time of filling, to have formulated the drug delivery device of Gao to provide a first layer that dissolves over 12 months because Gao discloses it as a possible embodiment and doing so would have yielded predictable results. See MPEP 2143 (A).
Regarding instant claim 16, Gao discloses the device provides a sustained release of a therapeutic agent (abstract) and that “[t]he goal of sustained-release systems is to maintain drug levels within the therapeutic range and ideally a constant level” (paragraph 3). “In order to achieve constant levels, drugs should be released from a delivery system at a rate that does not change with time (so called zero-order release)” (paragraph 4). Therefore, it would have been obvious to one of ordinary skill in the art, at the time of filling, to have provided the medication layers that dissolve at a constant rate to provide a constant rate of release.
Response to Arguments
First, on page 7 (last paragraph) and page 11 of their remarks, applicant argues that Gao does not disclose the newly amended limitation of a membrane layer which encapsulates a plurality of first medication layers, and a plurality of first medication layers which encapsulate a second membrane layer, and a second membrane layer which encapsulates a plurality of second medication layers. Second, on page 8 and 11 of their remarks, applicant argues Gao does not disclose or teach a placebo. Specifically, applicant argues that Gao teaches a non-therapeutic bioactive agent, not a non-bioactive substance, or placebo.
First, this argument is moot in view of the new rejection necessitated by amendment.
Second, this argument is not persuasive. Gao discloses: “In certain embodiments, the second layer further comprises the therapeutic agent which is contained within the core, although it may alternatively or additionally comprise a different therapeutic agent, or none at all” (emphasis added) [0011]. That is to say, Gao does not disclose a bioactive agent with no therapeutic effect, or the non-therapeutic bioactive agent asserted by applicant. Rather, Gao discloses the second layer does not require the presence of a therapeutic agent (i.e., bioactive agent) at all. One of ordinary skill in the art would have understood that a layer without a therapeutic agent (i.e., bioactive agent) would provide a placebo effect, insofar as the layer would not have delivered a bioactive agent during its sustained release. Therefore, the layer itself may be considered a placebo inducing medication.
2) Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (US2003/0118649 A1, publication date 06/26/2003) as applied to claims 9, 10 and 14-16 above, and further in view of Studd et al. (Studd j, Magos A., Obstet Gynecol Clin North Am. 1987 Mar;14(1):229-49) and Prior (J. Prior, Ovarian Hormone Therapy for Women with Early Menopause [online], 11/29/2013 [retrieved 4/12/25]).
Gao, which is taught above, differs from instant claim 12 insofar as it does not teach an implant which delivers a constant dose of hormones to a female body for 27 consecutive days, followed by a pause in delivering hormones for 3 days. Gao does disclose the device may be used to deliver hormones (paragraph 103). Gao also discloses the release rate may be controlled by the permeability of the membrane (paragraph 82) and that in certain embodiments the bioactive agent has a sustained release of at least two days or at least a month (paragraph 19).
Studd discloses that for menopause and premenstrual syndrome, hormone “[i]mplants represent a physiologic mode of therapy with many metabolic advantages over other routes” (abstract). Studd further discloses that “hormone implantation is simple and fast and obviates daily oral medication” (abstract).
Studd does not disclose a specific regimen for hormone treatment.
Prior discloses a method of ovarian hormone therapy (OHT) for women with early menopause (title). For the therapy, Prior recommends patients take estrogen on days 1-27 and no estrogen for the last 3-4 days of the month (p. 3, last paragraph). Prior recommends the 3-4 day break after 27 days of hormone treatment because “it is not normal to have continuously high estrogen levels all cycle” (p. 3, last paragraph).
It would have been obvious for one of ordinary skill in the art, at the time of filling, to have combined the subcutaneous implant taught by Gao with the methods taught by Prior, to arrive at the instantly claimed invention. One would have been motivated to use a subcutaneous implant for the hormone therapy because Studd discloses implants provide a simple, fast and metabolically advantages route for administering hormones. One would have been motivated to use, and had an expectation of success in using the subcutaneous device taught by Gao, because it is able to provide the alternating sustained releases (i.e., 27 days and 3-4 days) required by the methods taught by Prior. Additionally, one would have had an expectation of success because Gao discloses the subcutaneous device may be used to deliver hormones or none at all (i.e., a pause in hormone delivery).
Finally, In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). In the instant case, the three day break from hormone treatment overlaps with the range in the prior art and therefore a prima facie case of obviousness exists.
Therefore, it would have been obvious to one of ordinary skill in the art, at the time of filling, to have produced the drug delivery device (pellet) taught by Gao such that is delivered a constant dose of hormones for 27 days, followed by a pause in delivery of 3 days.
Response to Arguments
First, on page 7 (last paragraph) and page 11 of their remarks, applicant argues that Gao does not disclose a membrane layer which encapsulates a plurality of first medication layers and a plurality of first medication layers which encapsulate a second membrane layer. Second, on page 8 and 11 of their remarks, applicant argues Gao does not disclose or teach a placebo. Specifically, applicant argues that Gao teaches a non-therapeutic bioactive agent, not a placebo which is a non-bioactive substance.
These arguments are not persuasive. The claims stand rejected for the same reasons above and of record.
3) Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (US2003/0118649 A1, publication date 06/26/2003) as applied to claims 9, 10 and 14-16 above, and further in view of Handelsman (Clinical pharmacology of testosterone pellet implants, In: Nieschlag, E., Behre, H.M. (eds) Testosterone, 1998, p. 349-364) and Isaacs et al. (Annals of Translational Medicine, 2019 Dec; 7 (Suppl 8): S311), as evidenced by Rice et al. (Frontiers in Oncology, 2019, vol. 9, article 801).
Gao, which is taught above, differs from instant claim 13 insofar as it does not disclose the subdermal drug delivery device to deliver testosterone over 14 days, followed by delivery of an antiandrogenic drug over 14 days. Gao does disclose the device may be used to deliver hormones (paragraph 103). Gao also discloses the release rate may be controlled by the permeability of the membrane (paragraph 82) and that in certain embodiments the bioactive agent has a sustained release of at least a week (paragraph 19).
Handelsman discloses implantable pellets for testosterone therapy are cheap safe, effective (p. 350, paragraph 1, last 6 lines) and are superior in durability and stability of clinical effects as well as patient compliance (p. 261, section 12.9.3).
Handelsman does not disclose cyclical dosing of testosterone.
Isaacs discloses that when castration-resistant prostate cancer cells are cycled from low to supraphysiologic androgen (i.e., testosterone; STP) levels, suppressed proliferation and cell death results (p. 1, col. 2, lines 6-12). Isaac also discloses that “therapeutic advantage can be gained by cycling between short periods (i.e., 2 weeks) of SPT back to a castrate level of T” (p. 2, col. 2, lines 1-3). Issacs also discloses that castration therapy is known to include the administration of secondary hormones such as abiraterone (p. 1, para. 1), which is an antiandrogen, as evidenced by Rice in the abstract.
Isaacs does not disclose a subdermal implant for delivering the testosterone.
First, it is generally prima facie obvious to select a known material based on its suitability for its intended use. See MPEP 2144.07. In the present case, it would have been obvious to one of ordinary skill in the art, at the time of filling, to have used a secondary hormone such as abiraterone (i.e., antiandrogens) in the 2 week castration period of the treatment methods disclosed by Isaacs, because Isaacs discloses it as a suitable option for castration therapy. Therefore, it would have been obvious to administer 2 weeks of testosterone followed by two weeks of an antiandrogenic drug.
Second, it would have been obvious for one of ordinary skill in the art, at the time of filling, and in light of the advantages taught by Handelsman, to have combined the drug delivery device of Gao with the methods thought by Isaacs, to arrive at the claimed invention. One would have been motivated to formulated the drug delivery device taught by Gao to provide the therapy disclosed by Isaacs because of the known advantageous taught by Handelsman. One would have had an expectation of success because Gao discloses the layers of the drug delivery device can provide a sustained release of at least a week and may be loaded with hormones or no therapeutic agents at all.
Therefore, it would have been obvious to one of ordinary skill in the art, at the time of filling, to have produced a subcutaneous drug delivery device, as taught by Gao, which provides 14 days of high doses of testosterone and then 14 days of an antiandrogenic drug.
Response to Arguments
First, on page 7 (last paragraph) and page 11 of their remarks, applicant argues that Gao does not disclose a membrane layer which encapsulates a plurality of first medication layers and a plurality of first medication layers which encapsulate a second membrane layer. Second, on page 8 and 11 of their remarks, applicant argues Gao does not disclose or teach a placebo. Specifically, applicant argues that Gao teaches a non-therapeutic bioactive agent, not a placebo which is a non-bioactive substance.
These arguments are not persuasive. The claims stand rejected for the same reasons above and of record.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/C.T.W./Examiner, Art Unit 1612
/WALTER E WEBB/Primary Examiner, Art Unit 1612