DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Amendments to the Claims and Arguments/Remarks filed 16 April 2026, in response to the Office Correspondence dated 16 January 2026, are acknowledged.
The listing of Claims filed 16 April 2026, have been examined. Claims 1-42, and 44 are pending. Claims 16 and 17 are amended, claim 43 is canceled and no new claims have been added.
Information Disclosure Statement
The Information Disclosure Statements (IDS), filed 4 March, 18 March, and 08 May 2026, are acknowledged and have been considered.
Response to Amendment
Entry of the amendments to claims 16 and 17 are acknowledged and have been reviewed. The applicant has addressed the inconsistency between independent claim 1, requiring at least 60 wt% aromatase inhibitor, and amended dependent claims 16 and 17, reciting ranges beginning at “about 60 wt.%”. These ranges are now consistent with the base claim from which they depend. Accordingly, the indefinite rejection under 35 U.S.C. § 112(b) regarding this point for claim 1 is withdrawn, yet the previous point of rejection for claims 1 and 44 for failing to specify the release medium, temperature, surface area normalization methodology, sampling protocol, or whether release is measured in vitro or in vivo remains outstanding. Thus, the rejection of claims 1 and 44 and dependent claims 2-42 under 35 U.S.C. § 112(b) are maintained.
The applicant’s arguments are found to be unpersuasive for the reasons set forth below in the Response to Arguments. Accordingly, previous rejections under 35 U.S.C. § 103 are maintained or re-stated as appropriate.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 16 January 2026, since the art which was previously cited continues to read on the amended/newly cited limitations.
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 Applicant regards as his invention.
Claims 1-42 and 44 are rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claims 1 and 44 recite, “at a time period of between 300 to 350 hours a cumulative release is between 6 mg/cm² to about 7 mg/cm².” However, the claims fail to specify the release medium (e.g., in vitro buffer, saline, simulated body fluid, or in vivo conditions), temperature, surface area normalization methodology, sampling protocol, or whether the release is measured in vitro or in vivo. Without such measurement condition parameters, a person of ordinary skill in the art would not be able to determine with reasonable certainty whether a given device falls within the scope of the claims. In addition, the claim, as a device claim, does not clearly articulate the physical structure or composition responsible for achieving this result.
To overcome this rejection, the applicant is advised to define objective test conditions for release measurements. Dependent claims 2-42 are included in these rejections because they do not cure the defect noted above for claim 1, from which they depend.
Claim 44 is also rejected because it introduces ambiguity regarding the subject matter of the invention. Claim 44 recites that the implantable device “consists of the core”, yet retains the same performance-based release limitations as claim 1. The exclusion of membrane layers while maintaining identical release characteristics raises uncertainty regarding the claimed invention, as the specification does not reasonably demonstrate that a core-only device would inherently achieve the same cumulative release profile recited.
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-AlA 35 U.S.C. § 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AlA) 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.
Claims 1-7, 9, 11-42 and 44 are rejected under 35 U.S.C. § 103 as being unpatentable over Schneider (US-20190358167-A1; publication date: 28 November 2019) in view of Kragie (US-20040192598-A1; publication date 30 September 2004).
Regarding instant claims 1, 3 and 5, Schneider teaches “An implantable device for delivery of a macromolecular drug compound, the device comprising: a core having an outer surface, wherein the core comprises a core polymer matrix within which is dispersed a drug compound having a molecular weight of about 0.5 kDa or more, the polymer matrix containing a hydrophobic polymer…” (claim 1), wherein “In certain embodiments, the core polymer matrix may contain a semi-crystalline olefin copolymer. The melting temperature of such an olefin copolymer may, for instance, range from about 40° C. to about 140° C…as determined in accordance with ASTM D3418-15. Such copolymers are generally derived from at least one olefin monomer (e.g., ethylene, propylene, etc.) and at least one polar monomer that is grafted onto the polymer backbone and/or incorporated as a constituent of the polymer (e.g., block or random copolymers). Suitable polar monomers include, for instance, a vinyl acetate…” (¶[0034]) and “In one particular embodiment, for example, the core polymer matrix may contain an ethylene vinyl acetate polymer, which is a copolymer that is derived from at least one ethylene monomer and at least one vinyl acetate monomer.” (¶[0035]). Schneider further discloses, “…the polar monomeric content of the copolymer [vinyl acetate of ethylene vinyl acetate copolymer] may be selectively controlled to be within a range of from about 10 wt. % to about 60 wt. %...” (¶[0034]).
Schneider teaches drug loadings overlapping and encompassing the claimed range, including embodiments in which the therapeutic agent constitutes 60-80 wt% of the core (therapeutic agent macromolecular biologic bromelain (¶[0056]) is present in the core at 80 wt. % (¶[0058], Table 1, Example 1 and ¶[0060], Table 2, Examples 5-7) or is present in the core at 60 wt. % (¶[0058], Table 1, Example 2; ¶[0062], Table 3, Examples 8-13; ¶[0064], Table 4, Examples 14-18; ¶[0066], Table 5, Examples 19-20; ¶[0068], Table 6, Examples 21-23; ¶[0073], Table 8, Examples 28-30)). Thus, the claimed minimum of 60 wt% is taught.
Moreover, the instant specification recites, “Typically, therapeutic agents will constitute from about 5 wt. % to about 60 wt. %... In certain embodiments, therapeutic agents constitute from about 40 wt. % to about 80 wt. % of the core, such as from about 50 wt. % to about 70 wt. % of the core, such as about 60 wt. % of the core.” (¶[0025]; see also instant claims 16 and 17) and does not appear to support a range greater than about 80 wt. %. The instant specification example embodiments select exemestane core loading of 10% (¶[0074], Table 1, Examples 1, 4 and 5; ¶[0078], Table 2, Examples 6 and 8; ¶[0079], Table 3, Formulations 1 and 4), 40% (¶[0074], Table 1, Example 2) and 60% (¶[0074], Table 1, Example 3; ¶[0078], Table 2, Example 7; ¶[0079], Table 3, Formulation 3).
Schneider also teaches that release rates and cumulative delivery are controlled by routine adjustment of polymer composition, drug loading, membrane structure, and geometry (see ¶[0027]-[0031]), all of which are expressly disclosed variables. Thus, the instant claimed cumulative release window limitation of 6-7 mg/cm² at 300-350 hours represents an optimization of known result-effective variables, achievable through routine experimentation.
Schneider does not exclude the use of small molecules (see ¶[0027] and ¶[0036]), and teaches a general-purpose implantable drug delivery platform. However, Schneider does not teach the use of the device for delivering one or more aromatase inhibitors.
Kragie teaches an implantable device composed of polymers or polymer matrix for sustained-release (claim 8) of aromatase inhibitor formulations (claim 6). Thus, Kragie teaches sustained-release aromatase inhibitor therapy, in which the limitation of the aromatase inhibitor having a molecular weight of less than 350 g/mol is an inherent property of the aromatase inhibitors explicitly disclosed by Kragie (¶[0031]; aminoglutethimide: ~231.3 g/mol (C₂₀H₂₃N₃O₂); anastrozole (Arimidex): ~293.4 g/mol (C₂₀H₂₃N₃); fadrozole: ~277.3 g/mol (C₁₄H₁₅N₅); roglethimide: ~273.3 g/mol (C₁₆H₂₃NO₂); atamestane: ~300.4 g/mol (C₂₀H₂₈O₂); exemestane (Aromasin): ~296.4 g/mol (C₂₀H₂₄O₂); formestane (Lentaron): ~288.4 g/mol (C₁₈H₂₄O₂); and vorozole: ~293.3 g/mol (C₁₆H₁₁N₃O), to name a few). Selecting a known drug class and reciting its inherent molecular weight does not impart patentable distinction (see In re Best, 562 F.2d 1252 (CCPA 1977)).
Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to modify the general-purpose implantable drug delivery platform of Schneider to deliver one or more aromatase inhibitors, inherently having a molecular weight of less than 350 g/mol, instead of a macromolecular compound or in addition to a macromolecular, because Schneider teaches a versatile delivery device capable of controlled release and targeted delivery for administering therapeutic agents and Kragie demonstrates that aromatase inhibitors are well-known therapeutic agents with established medical uses when administered via sustained-release devices. The substitution of one known therapeutic agent for another known therapeutic agent with predictable diffusion behavior remains is an obvious choice.
Achieving a cumulative release of 6-7 mg/cm² at 300-350 hours would be an optimization of known result-effective variables, achievable through routine experimentation (see In re Aller, 220 F.2d 454 (CCPA 1955) and In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003)), given that Schneider teaches that release rates and cumulative delivery are controlled by routine adjustment of polymer composition, drug loading, membrane structure, and geometry. The Applicant has not demonstrated that the claimed release window is critical, unexpected, or unobtainable using the prior art teachings.
One skilled in the art would recognize that substituting a small-molecule aromatase inhibitor for a macromolecular compound is a predictable variation, given that drug delivery devices are routinely adapted for different classes of therapeutics (e.g., proteins vs. small molecules) based on known pharmacokinetic principles. No unexpected modifications to the device are required to achieve the claimed delivery of an aromatase inhibitor in the known delivery system (see KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007) and In re Dillon, 919 F.2d 688 (Fed. Cir. 1990)).
Regarding instant claim 44, distinguished from instant claim 1 “comprising a core” (must include a core but may also include unrecited structural elements) with “consists of the core” (must include a core and exclude any other structural elements of significance) requires a single-layer, core-only device including the exact components recited for claim 1. Thus, the limitations of instant claim 1 as it applied to instant claim 44 are taught as described above. The same reasoning regarding molecular weight, drug loading, and cumulative release applies equally to claim 44.
Further, Schneider expressly teaches core-only implant embodiments, including embodiments without membrane layers (¶[0027], ¶[0029], and ¶[0039]). Kragie’s sustained-release aromatase inhibitor formulations are likewise independent of auxiliary membranes. The exclusion of optional membrane layers that Schneider teaches as non-essential does not confer patentability where the core itself remains structurally and functionally obvious (see In re Larson, 340 F.2d 965, 968 (CCPA 1965), wherein the elimination of an element and its function, if it does not change the principle or mode of operation of the invention, is not considered patentable). The claimed “consists of” language merely excludes optional elements that Schneider teaches as non-essential.
Regarding instant claim 2, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider teaches, an implantable device with a polymer melt flow index of from about 0.2-100 grams per 10 minutes as determined in accordance with ASTM D1238-13 at 190° C and a load of 2.16 kilograms (claim 17), but does not specifically disclose wherein the core polymer matrix has a melt flow index of from about 1-400 grams per 10 minutes as determined in accordance with ASTM D1238-20 at 190°C and a load of 2.16 kilograms.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to use the lower bound of the claimed melt flow index range because it overlaps and falls within the prior art range (0.2–100 g/10 min), suitable for similar applications, and extend by broadening the melt flow index upper bound in the prior art to include the claimed range of 100 to 400 g/10 min as a matter of a routine optimization, known in polymer processing (e.g., adjusting molecular weight, plasticizers, or processing conditions). No unexpected results or criticality has been shown for the claimed range (1–400 g/10 min) compared to the prior art (0.2–100 g/10 min) and pertinent ASTM testing conditions (D1238, 190°C, 2.16 kg) are identical, meaning the claimed range is measured the same way as in the prior art ((see In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003) and KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007)).
Regarding instant claim 4, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider further discloses wherein, “the core polymer matrix constitutes from about 40 wt. % to about 95 wt. %...of the core.” (¶[0029]) and in Table 1, Example 4 the core polymer matrix constitutes 20 wt. % of the core (¶[0058]). The claimed numerical range is encompassed within the range disclosed in the prior art and no unexpected results or criticality have been shown, and is thus obvious.
Regarding instant claim 6, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above, but does not specifically disclose wherein the core polymer matrix includes a first and second ethylene vinyl acetate. However, Schneider discloses the use of different types of ethylene vinyl acetate copolymers that may be formed and/or blended as, “Any of a variety of techniques may generally be used to form the ethylene vinyl acetate copolymer with the desired properties as is known in the art.” (¶[0035]). Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to create the implantable device disclosed by Schneider wherein the core polymer matrix includes a first ethylene vinyl acetate copolymer and a second ethylene vinyl acetate copolymer, through routine experimentation in view of the knowledge of a person having ordinary skill in the art and the claimed invention fall entirely within the scope of the broader disclosure of the prior art.
Regarding instant claim 7, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider does not teach wherein the use of one or more aromatase inhibitors is comprised of anastrozole, exemestane, letrozole, and combinations thereof. However, Kragie explicitly discloses the use of these aromatase inhibitor compounds (claim 6, xiii). Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to use the specific aromatase inhibitors disclosed by Kragie to the invention of instant claim 1 because the compounds are specifically disclosed within the scope of the prior art.
Regarding instant claim 9, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider does not teach the use of one or more aromatase inhibitors and one or more selective estrogen receptor modulators. Kragie discloses an implantable device further comprising at least one other therapeutic agent including a selective estrogen receptor modulator (claim 1) as, “EFR agents include the group defined as selective estrogen receptors ligands and modulators.” (¶[0035]). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to add co-administration of one or more aromatase inhibitors and one or more selective estrogen receptor modulators to invention of instant claim 1 with a reasonable expectation of success based on co-administration disclosed by Kragie and one would be motivated to do so using the device design disclosed by Schneider for benefits gained by synergistic therapy.
Regarding instant claims 11-13, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider further discloses, wherein the device has a generally circular cross-sectional shape (claim 2), is in the form of a cylinder (claim 4), and is in the form of a disc (claim 5). Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to incorporate the instant claim limitations to the instant claim 1 invention of Schneider in view of Kragie because the claimed limitations are expressly taught by the prior art.
Regarding instant claims 14, 15 and 18-21, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider teaches, “Of course, the actual dosage level of the drug compound delivered will vary depending on the particular drug compound employed and the time period for which it is intend to be released. The dosage level is generally high enough to provide a therapeutically effective amount of the drug compound to render a desired therapeutic outcome, i.e., a level or amount effective to reduce or alleviate symptoms of the condition for which it is administered. The exact amount necessary will vary, depending on the subject being treated, the age and general condition of the subject to which the macromolecular drug compound is to be delivered, the capacity of the subject's immune system, the degree of effect desired, the severity of the condition being treated, the particular macromolecular drug compound selected and mode of administration of the composition, among other factors. An appropriate effective amount can be readily determined by one of skill in the art. For example, an effective amount will typically range from about 5 pg to about 200 mg…” (¶[0031]). Schneider also teaches wherein, “...the implantable device can release the drug compound for a time period of about 5 days or more, in some embodiments about 10 days or more, in some embodiments from about 20 days to about 60 days, and in some embodiments, from about 25 days to about 50 days (e.g., about 30 days).” (¶[0030]).
Schneider does not explicitly teach wherein the core is loaded with from about 200-500 mg of one or more aromatase inhibitors, wherein the device is capable of releasing the therapeutic agent for a time period of about 3 or 12 months or more, or wherein the one or more aromatase inhibitors are released from the device to deliver from about 0.1-2 mg of aromatase inhibitor per day.
Kragie teaches “The aromatase inhibitor activity, and the concentration range of inhibitor effect, can be identified by dose-response evaluation of the agent in the assays of aromatase enzyme activity. Probable target tissue concentrations of aromatase inhibitor can be estimated by assessing subject's inhibitor exposure and the bioavailability of the aromatase agent at the target site.” (¶[0029]) and sustained-release embodiments (claim 8).
Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to add the missing limitations of loading 50-500 mg of one or more aromatase inhibitors releasing 0.1-2 mg of aromatase inhibitor per day for a time period of about 21 days to 12 months or more to the invention of instant claim 1 in view of the knowledge of a person having ordinary skill in the art and arrive at the instant invention through routine experimentation.
Regarding instant claims 16 and 17, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider teaches wherein the drug compounds constitute from about 5-60 wt. % of the core of the implantable device (claim 6) and wherein the therapeutic agent constitutes from about 60-80 wt. % of the core in Table 1, Examples 3 and 4 (¶[0058]). Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to create the implantable device of instant claim 1 disclosed by Schneider in view of Kragie wherein the therapeutic agent constitutes from about 40-80 wt. % of the core because the claimed range is expressly taught by the prior art.
Regarding instant claim 22, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider further teaches, “The core may also optionally contain one or more excipients if so desired, such as… plasticizers…” (¶[0038]). Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to create the implantable device of instant claim 1 disclosed by Schneider in view of Kragie wherein the core polymer matrix comprises one or more plasticizers because the option to include plasticizers as an excipient is expressly taught by the prior art.
Regarding instant claims 23 and 24, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider further teaches, “The membrane layer(s) and/or the core may also optionally contain one or more excipients as described above, such as radiocontrast agents, hydrophilic compounds…When employed, the optional excipient(s) typically constitute from about 0.01 wt. % to about 60 wt. %...” (¶[0048]). Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to create the implantable device of instant claim 1 disclosed by Schneider in view of Kragie wherein the core polymer matrix comprises one or more hydrophilic compounds present in an amount of from about 1-60 wt. % to control release of the therapeutic agent from the implantable device, because the inclusion as an excipient at the claimed ranges is expressly taught by the prior art.
Regarding instant claim 25, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider further teaches “One or more nonionic, anionic, and/or amphoteric surfactants may also be employed to help create a uniform dispersion.” (¶[0050]). Schneider does not explicitly state that the therapeutic agent is homogenously dispersed within the core polymer matrix, however, because Schneider does not disclose otherwise, the therapeutic agent is presumed to be homogeneously dispersed, as conventional blending methods and techniques used for drug-polymer blends (e.g., solvent casting, melt extrusion, spray drying) are well-known in the art to produce uniform dispersions (In re Kubin, 561 F.3d 1351 (Fed. Cir. 2009)) and where intentional non-uniform dispersions (e.g., deliberately engineered core-shell or gradient systems) have not been specified, one skilled in the art would default to standard manufacturing practices that yield homogeneity (see MPEP 2144.05).
Regarding instant claims 26-30, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above. Schneider further teaches a first membrane layer positioned adjacent to an outer surface of the core as, “The core 140 defines an upper outer surface 161 on which is positioned a first membrane layer 120...” (¶[0045]) and “…a first membrane layer may contain a first polymer matrix and a second membrane layer may contain a second polymer matrix... Examples of suitable ethylene vinyl acetate copolymers that may be employed…” (¶[0046]), indicating wherein the first membrane layer may comprise a first membrane polymer matrix containing an ethylene vinyl acetate copolymer, as per the limitations of the instant claim. Schneider further discloses wherein the first membrane layer may be free of the therapeutic agent as, “In certain embodiments, for example, the membrane layer may be generally free of such a drug compound.” (¶[0029]).
Additionally, Schneider teaches wherein the ethylene vinyl acetate copolymer may constitutes an entire polymer content of the first membrane polymer matrix as, “Regardless of the particular configuration employed, the membrane layer(s) generally contain a membrane polymer matrix that contains a hydrophobic polymer, such as described above. The polymer matrix typically constitutes from about 30 wt. % to 100 wt. %, in some embodiments… of a membrane layer. When employing multiple membrane layers, it is typically desired that each membrane layer contains a polymer matrix that includes such a hydrophobic polymer. For example, a first membrane layer may contain a first polymer matrix and a second membrane layer may contain a second polymer matrix. In such embodiments, the first and second polymer matrices each contain a hydrophobic polymer, which may be the same or different. Likewise, the hydrophobic polymer used in the membrane layer may also be the same or different the hydrophobic polymer employed in the core… Examples of suitable ethylene vinyl acetate copolymers that may be employed include those available from Celanese under the designation ATEVA® (e.g., ATEVA® 4030AC or 2861A).” (¶[0046]), “The membrane layer(s) and/or the core may also optionally contain one or more excipients as described above, such as... plasticizers...” (¶[0048]) and “Regardless of the particular configuration employed, the membrane layer(s) generally contain a membrane polymer matrix that contains a hydrophobic polymer, such as described above...” (¶[0046]). The instant claim limitations fall within or overlap with the invention specifications disclosed by Schneider and thus would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date.
Regarding instant claim 31, Schneider in view of Kragie discloses the implantable device of instant claim 26, as described above. Schneider further discloses wherein, “...In certain embodiments, the core polymer matrix may contain a semi-crystalline olefin copolymer... The melting temperature of such an olefin copolymer may, for instance, range from about 40° C. to about 140° C…as determined in accordance with ASTM D3418-15...” (¶[0034]). The instant claim limitations fall are encompassed with the invention specifications disclosed by Schneider and thus would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date.
Regarding instant claim 32, Schneider in view of Kragie discloses the implantable device of instant claim 26, as described above. Schneider further teaches, “As indicated above, the core polymer matrix contains at least polymer that is generally hydrophobic in nature… Typically, the melt flow index of the hydrophobic polymer ranges from about 0.2 to about 100 g/10 min…, as determined in accordance with ASTM D1238-13 at a temperature of 190° C. and a load of 2.16 kilograms.” (paragraph [0033]). Therefore, the ethylene vinyl acetate copolymer of the first membrane polymer matrix having an identical melt flow index (i.e., 0.2–100 g/10 min) under the same test conditions (i.e., 190°C, 2.16 kg load) in accordance with ASTM D1238-20 is obvious, given the ASTM standard version (i.e., D1238-13 vs. D1238-20) is the only difference, wherein the version change imparts minor updates (e.g., editorial changes, precision improvements) and does not alter the fundamental measurement principle. It therefore, would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to use the instant claim limitations, as the claimed melt flow index range is identical to that of Schneider and is expected to be equivalent under either ASTM standard version and selecting a disclosed species of ethylene vinyl acetate from a prior art hydrophobic polymer genus is obvious absent unexpected properties (see In re Baird (Fed. Cir. 1994)).
Regarding instant claims 33-42, Schneider in view of Kragie discloses the implantable device of instant claim 26, as described above. Schneider discloses, “...Regardless of the particular monomers selected, the present inventors have discovered that certain aspects of the copolymer can be selectively controlled to help achieve the desired release properties. For instance, the polar monomeric content of the copolymer [vinyl acetate monomer content for ethylene vinyl acetate copolymer] may be selectively controlled to be within a range of from about 10 wt.% to about 60 wt.%...” (¶[0034]). Schneider further discloses “...Of course, hydrophilic polymers that are coated or otherwise encapsulated with a hydrophobic polymer are also suitable for use in the core polymer matrix...” (¶[0033]) and “...To help further control the release rate from the implantable device, for example, a hydrophilic compound may also be incorporated into the polymer matrix of the membrane layer(s) that is soluble and/or swellable in water...” (¶[0049]).
Additionally, Schneider teaches “The membrane layer(s) and/or the core may also optionally contain one or more excipients as described above, such as radiocontrast agents, hydrophilic compounds…When employed, the optional excipient(s) typically constitute from about 0.01 wt. % to about 60 wt. %...” (¶[0048]). Schneider also teaches “...To help further control the release rate from the implantable device, for example, a hydrophilic compound may also be incorporated into the polymer matrix of the membrane layer(s) that is soluble and/or swellable in water...” (¶ [0049]) and “...wherein the hydrophilic polymer includes ... water-soluble polysilane, water-soluble silicone, water-soluble polyurethane, or a combination thereof...” (claim 29).
Moreover, Schneider teaches “...The core 140 defines an upper outer surface 161 on which is positioned a first membrane layer 120 and a lower outer surface 163 on which is positioned a second membrane layer 122...” (¶[0045]) and “...a first membrane layer may contain a first polymer matrix and a second membrane layer may contain a second polymer matrix...” (¶[0046]), wherein “...the first and second polymer matrices each contain a hydrophobic polymer, which may be the same or different... Examples of suitable ethylene vinyl acetate copolymers that may be employed include those available from Celanese under the designation ATEVA® (e.g., ATEVA® 4030AC or 2861A)...” (¶[0046]), therefore the two layers may both be ethylene vinyl acetate with different vinyl acetate contents and “...In certain embodiments, for example, the membrane layer may be generally free of such a drug compound...” (¶[0029]).
And finally, Schneider discloses the two standard polymer processing technique for implantable devices as, “Regardless of the particular components employed, the core may be formed through a variety of known techniques, such as by hot-melt extrusion…” (¶[0039]) and “...Once melt blended together, the resulting polymer composition may be in the form of pellets, sheets, fibers, filaments, etc., which may be shaped into the core using a variety of known shaping techniques, such as... compression molding...” (¶[0042]).
Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to create the implantable device of instant claim 1 disclosed by Schneider in view of Kragie including all the limitations of instant claims 33-42, because they are discernably taught in the prior art by Schneider.
Claims 1 and 8 are rejected under 35 U.S.C. § 103 as being unpatentable over Schneider (US-20190358167-A1; publication date: 28 November 2019) in view of Kragie (US-20040192598-A1; publication date 30 September 2004) and in further view of Wijzen (US-20150202076-A1; publication date 23 July 2015).
Regarding instant claim 8, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above, from which instant claim 8 depends. However, Schneider and Kraige do not explicitly teach the use of one or more aromatase inhibitors and one or more glucocorticoids.
Wijzen discloses an intrauterine device (IUD) that may be implantable (¶[0018]), wherein the device may be configured to deliver a therapeutic agent comprising aromatase inhibitors (¶[0071]) and “The composition may comprise a second active pharmaceutical ingredient… selected from the group of…glucocorticoids…” (¶[0073]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to combine these references, and to create the implantable device further comprising at least one or more glucocorticoids to the device taught by Schneider used with the aromatase inhibitors taught by Kragie for synergistic therapy, because glucocorticoids were known to be capable of and used for preventing and/or suppressing abnormal and/or irregular endometrial bleeding, possible with aromatase inhibitor use (see Wijzen ¶[0073]).
Claims 1 and 10 are rejected under 35 U.S.C. § 103 as being unpatentable over Schneider (US-20190358167-A1; publication date: 28 November 2019) in view of Kragie (US-20040192598-A1; publication date 30 September 2004), and in further view of Loeffler (US-20100047306-A1; publication date 25 February 2010).
Regarding instant claim 10, Schneider in view of Kragie discloses the implantable device of instant claim 1, as described above, in which instant claim 10 depends. However, Schneider and Kraige do not explicitly teach the use of one or more aromatase inhibitors and one or more bisphosphonates.
Kraige teaches the use of aromatase inhibitors for breast cancer can produce adverse effects of estrogen-depletion, such as effects on bone resorption (¶[0085]) and that aromatase expression is important in slowing the rate of postmenopausal bone loss (¶[0008]), thus inhibiting aromatase can impact postmenopausal bone loss.
Loeffler discloses a implant device comprising bisphosphonates within a polymer [microparticles] for the treatment and prevention of proliferative diseases including cancer (Abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to combine these references, and to create the implantable device further comprising at least one or more bisphosphonates to the device taught by Schneider used with the aromatase inhibitors taught by Kragie for synergistic therapy, because bisphosphonates are known to be effective in treating against malignant diseases such as cancer and prevent postmenopausal bone loss or other forms of bone loss secondary to or due to medication (see Loeffler ¶[0001]-[0002] and ¶[0115]-[0116]) which could provide synergistic therapeutic effects in combination with aromatase inhibitors to potentially help combat possible bone loss side-effects caused by aromatase inhibitors.
Response to Arguments
Applicant Arguments/Remarks of the reply, filed 16 April 2026, have been fully considered but are not persuasive.
The applicant contends that the pending claims satisfy the requirements of 35 U.S.C. § 112 and requests withdrawal of the indefiniteness rejections under 35 U.S.C. § 112(b). The applicant has not, however, addressed the substantive deficiencies identified in the 16 January 2026, Office Correspondence. Thus, the rejection of claims 1 and 44, and therefore dependent claims 2-42 as well, under 35 U.S.C. § 112(b) for failing to specify the release medium, temperature, surface area normalization methodology, sampling protocol, or whether release is measured in vitro or in vivo remains outstanding. The applicant’s mere statement of disagreement, without amendment to cure the defect or substantive argument explaining why a person of ordinary skill in the art would nevertheless be able to determine the scope of the claims with reasonable certainty, is unpersuasive (see MPEP § 2173.05(g); release rate limitations require sufficient test conditions to avoid indefiniteness).
Independent claims 1 and 44 continue to recite, “at a time period of between 300 to 350 hours a cumulative release is between 6 mg/cm² to about 7 mg/cm².” The claims remain indefinite because they fail to define the objective measurement conditions necessary to determine claim scope with reasonable certainty. The claims do not specify, inter alia whether release is measured in vitro or in vivo; the release medium; temperature; agitation conditions; sampling intervals; replenishment protocol; whether “mg/cm²” is normalized to initial exposed geometric surface area, effective exposed area during erosion, or another reference surface.
Because release kinetics in polymer-controlled diffusion systems are highly sensitive to these variables, persons of ordinary skill in the art would not be able to determine with reasonable certainty whether a given device falls within the scope of the claims. Further, the limitation is drafted purely as a functional result without identifying the structural parameters that necessarily produce the claimed release behavior. The absence of objective testing conditions renders the metes and bounds of the claims uncertain.
The applicant has failed to address this deficiency. Therefore, claims 1 and 44, and dependent claims 2-42, remain rejected under 35 U.S.C. § 112(b) for failure to specify measurement conditions for the cumulative release limitation, as previously set forth. The applicant is again advised to amend the claims to provide objective test conditions for release measurements.
The applicant argues that a prima facie case of obviousness has not been established because the examiner has not articulated a motivation to combine Schneider and Kragie with a reasonable expectation of success. The applicant further argues that substituting a small-molecule aromatase inhibitor into Schneider’s macromolecule-focused device would yield unpredictable release behavior. The arguments have been considered, but are not persuasive.
The applicant contends that the examiner relies only on the generalized proposition that both references concern sustained localized drug delivery, which would render any device reference combined with any drug reference presumptively obvious. However, the motivation is not merely that both references share a general field, but rather that Schneider teaches a versatile implantable drug delivery platform explicitly designed for “therapeutic, prophylactic, and diagnostic agents” (¶[0036]) and Kragie teaches that aromatase inhibitors are well-suited for sustained-release therapy (claim 8).
The rejection is based on the combined teachings of Schneider’s configurable implantable controlled-release polymer platform in which release properties are governed by known adjustable parameters including polymer composition, drug loading, membrane architecture, and geometry and Kragie’s sustained-release administration of aromatase inhibitors as recognized therapeutic agents. A person of ordinary skill seeking to deliver aromatase inhibitors via a sustained-release implant would be motivated to employ the controlled-release platform taught by Schneider. The relevant inquiry is not whether Schneider’s working examples emphasize macromolecules, but what the combined teachings would have suggested to a person of ordinary skill in the art. The fact that Schneider exemplifies macromolecular compounds does not limit its teachings to macromolecules, wherein a reference is not limited to its preferred embodiments.
The specification expressly teaches that the device is suitable for delivery of therapeutic, prophylactic, and diagnostic agents broadly, and that release behavior may be tailored by modification of known variables. The “macromolecular” limitation is a claim limitation of certain embodiments, not a definitional boundary of the disclosure (see In re Keller, 642 F.2d 413, 425 (CCPA 1981), wherein the test is what the combined teachings would have suggested to one of skill, not whether the references are identical in purpose). The applicant’s attempt to read a macromolecule-only limitation into Schneider is unsupported. A person of ordinary skill seeking sustained local delivery of known aromatase inhibitors would have had reason to employ Schneider’s known adjustable implant platform (see KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007) and In re Keller, 642 F.2d 413 (CCPA 1981)).
The applicant further argues that Schneider’s emphasis on macromolecules defeats a reasonable expectation of success in placing small-molecule aromatase inhibitors into a matrix designed for macromolecular diffusion because it would yield unpredictable release behavior. This argument is not persuasive. This argument ignores the well-established and routine adjustment of drug release from polymer matrices by varying drug loading, polymer composition, and device geometry as ordinary optimization in the art. Further, Schneider does not teach that the platform is inoperative for lower-molecular-weight compounds. Rather, Schneider teaches that release behavior is controlled through routine adjustment of known formulation parameters, wherein release rates and cumulative delivery are controlled by routine adjustment of known formulation parameters and result-effective variables (¶[0027]-[0031]).
The fact that different drugs may have different diffusion coefficients does not render the adaptation of a known delivery platform unpredictable, it identifies formulation variables requiring optimization, that one of skill in the art would routinely adjust parameters to achieve a desired release profile. Routine optimization of known result-effective variables does not render a claimed invention nonobvious. Indeed, the instant specification itself teaches that release rates can be controlled by adjusting variables such as drug loading, polymer composition, and membrane layers. Adjustments of such is foundational in the art of controlled-release drug delivery.
The claimed cumulative release window of 6-7 mg/cm² at 300-350 hours is precisely the kind of optimization that is predictable and achievable through routine experimentation (see In re Aller, 220 F.2d 454, 456 (CCPA 1955), wherein the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation). The applicant has not provided evidence that small-molecule aromatase inhibitors would be incompatible with Schneider’s matrix, or that achieving sustained release would have been technically unpredictable. Accordingly, one of ordinary skill in the art would have a reasonable expectation of success in placing small-molecule aromatase inhibitors into the matrix taught by Schneider by conducting routine experimental optimization of known result-effective variables within the framework taught by Schneider.
The applicant further argues that the claimed cumulative release of 6-7 mg/cm² at 300-350 hours is not taught. This argument is unpersuasive. Schneider expressly teaches that cumulative release is governed by controllable variables including polymer composition, drug loading, membrane configuration, and device geometry. The claimed release window therefore represents a target result obtainable by routine optimization of known variables.
The applicant has not submitted any objective evidence of unexpected results or criticality of the claimed range, or that the claimed release profile is unobtainable from the prior art platform. Attorney argument alone is insufficient to rebut the prima facie case. The mere recitation of a cumulative release range, without any comparison data demonstrating that the claimed range produces results unexpectedly different from what one of skill would have predicted, does not rebut a prima facie case of obviousness (see In re Dillon, 919 F.2d 688, 692-93 (Fed. Cir. 1990), wherein evidence of unexpected results establishes that the claimed composition achieves something the prior art did not teach or suggest, or that the claimed composition achieves unexpectedly better results than the closest prior art).
In addition, the applicant emphasizes the recitation of “the one or more aromatase inhibitors having a molecular weight of less than 350 g/mol.” Kragie expressly identifies aromatase inhibitors that inherently satisfy that molecular-weight limitation. Recitation of an inherent property of a known selected species does not impart patentable distinction (see In re Best, 562 F.2d 1252 (CCPA 1977)).
The claim rejections under 35 U.S.C. § 103 set forth in the previous Office Correspondence are maintained. The newly amended dependent claims 16 and 17, do not overcome the prior art because Schneider expressly teaches therapeutic-agent loadings overlapping the claimed ranges, including 60-80 wt% (80 wt% in ¶[0058], Table 1, Example 1; ¶[0060], Table 2, Examples 5-7, and 60 wt% in ¶[0058], Table 1, Example 2; ¶[0062], Table 3, Examples 8-13; ¶[0064], Table 4, Examples 14-18; ¶[0066], Table 5, Examples 19-20; ¶[0068], Table 6, Examples 21-23; ¶[0073], Table 8, Examples 28-30). Thus, the claimed ranges are within the prior art disclosures. Selecting a drug loading from within a disclosed range is a matter of routine optimization and does not confer patentability absent evidence of unexpected results or criticality (see In re Peterson, 315 F.3d 1325, 1332-33 (Fed. Cir. 2003)).
Conclusion
No claims are allowed.
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 (87 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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/RL Scotland/
Examiner, Art Unit 1615
/Jeffrey T. Palenik/Primary Examiner, Art Unit 1615
Prosecution Insights