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
Claims 1-25 filed 12/09/2024 are pending and accordingly, they are under examination to which the following grounds of rejections are applicable.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/09/2024 was filed before the mailing date of the instant first action on the merits. The submission thereof is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner and signed and initialed copy is enclosed herewith.
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 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3, 5, 20 and 22-25 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by DeNeui et al., “Subcutaneous testosterone pellet implants – understanding the role of triamcinolone,” Evexias health solutions, 2018, pp. 1-6 (of record in application 18/121576: PTO-892 of 07/19/2023, hereinafter “DeNeui”).
Applicant claims the below claims 1 and 20 filed on 12/09/2024:
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Prior Art
DeNeui discloses subcutaneous implant comprising testosterone pellet and trace amount of triamcinolone for treating testosterone deficiency (see entire document including page 2, first/second para. and page 3, last para. treating andropausal hormone therapy), and that is, DeNeui discloses that about 5900 patients received testosterone implant infused with trace amounts of triamcinolone, and here, testosterone is used in an amount of 200mg pellet (=about 99%, 200/200.04) (page 3) which reads on the instant testosterone and the amount of prior art touches about 99% and triamcinolone is used in an amount of 0.04mg (=40 mcg =about 0.02%, 0.04/200.04) (page 3) which reads on the instant triamcinolone and the amount of prior art is also within the claimed range of about 0.005 to about 0.05% or about 0.01 to about 0.04%; and the testosterone/triamcinolone pellet formulation contains binders and lubricating agents such as stearic acid or cholesterol or (page 4) which reads on the claimed excipients and when the patients received testosterone implants infused with trace amounts of triamcinolone, the rates of post insertion pellet extrusions was reduced by greater than 50%, and zero adverse events from the triamcinolone infused pellets were observed with patients reported less discomfort at insertion site post procedure compared to prior insertions without triamcinolone (page 3); and all complications of skin hypopigmentation and fat atrophy may be greatly reduced if appropriate potency, dosage, and solubility are used, and utilization of very low doses of corticosteroid, less than 1mg/ml can negate these adverse outcomes (page 3, first para.) wherein “less than 1mg/ml” corresponds to less than 0.1 percent which embraces 0.005% or about 0.05%. The combination pellet is released in a sustained manner over 5 months (page 3) (instant claims 1, 3, 5, 20 and 22-25).
In light of the foregoing, instant claims 1, 3, 5, 20 and 22-25 are anticipated by DeNeui.
Claim Rejections - 35 USC §103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
As indicated above, the present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-7 and 14-25 are rejected under 35 USC 103 as being obvious over DeNeui et al., “Subcutaneous testosterone pellet implants – understanding the role of triamcinolone,” Evexias health solutions, 2018, pp. 1-6 (of record in application 18/121576: PTO-892 of 07/19/2023, hereinafter “DeNeui”) as applied to instant claims 1, 3, 5, 20 and 22-25 in view of Shuler et al. (US2006/0252049A1, of record in application 18/121576: PTO-892 of 07/19/2023, hereinafter “Shuler”).
Applicant claims the claims 1, 14 (below) and 20 filed on 12/09/2024:
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Determination of the scope and content of the prior art (MPEP 2141.01);
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness Rational and Motivation (MPEP 2142-2143)
DeNeui was discussed with respect to instant claims 1, 3, 5, 20 and 22-25.
DeNeui discloses implantable pellets containing about 99% testosterone, 0.04% triamcinolone, and excipients such as binder and lubricants, such as stearic acid and the pellets are released in a sustained manner for 5 months for e.g., treating adropausal hormone therapy, e.g., low level of testosterone as noted above. However, DeNeui does not expressly teach pellet hardness of no more about 75 Newtons. However, DeNeui provides pellet form of implant and pellet hardness is usually measured by e.g., compression/fracture force and thus, a skilled artisan would have had reason to optimize or adjust the compression conditions/hardness of implant containing testosterone and triamcinolone to obtain sufficient mechanical integrity for manufacture, handling, and implantation, in the absence of criticality (instant claims 14-19 and 21).
However, DeNeui does not expressly teach the amount of testosterone of instant claims 2 and 15, the amount of coating agent of instant claim 4, the amount of binding agent of instant claim 6, and ethylcellulose of instant claim 7. The deficiencies are cured by Shuler.
Shuler teaches an implantable pharmaceutical composition in the form of a pellet (e.g., claim 24 of prior art) for subcutaneous implantation to animal including human (e.g., [0011]) that embraces male and/or female comprising at least one bioactive agent such as triamincinolonic acetate (=triamcinolone acetate) in an amount of about 1-100% by weight of the implant, which bioactive agent reads on the claimed triamcinolone. As evidenced by US5512055A (Table 5) and US5731303A (Example 1), triamincinolone is the same as triamcinolone; and at least one pharmaceutical agent in an amount of about 50-99% such as steroid hormones, e.g., testosterone, dexamethasone, corticosteroids, prednisolone, hydrocortisone, cortisone acetate, flunisolide and triamcinolone acetate and mixtures thereof, among them, testosterone is particularly preferred steroid hormones (e.g., [0021] and claims 1- 3, 9, 11, 17, 20, 30-33, 37-39 and 49 of prior art) in which the amount of steroid hormone overlaps the instant ranges of about 93 to about 97% (instant claim 2), Please see MPEP 2144.05(I): 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). Further Shuler teaches the composition further comprise additives, and/or excipients such as stearic acid, ethyl cellulose (=EC) and polyoxyethylene (e.g., [0025] and claim 22 of prior art), adjuvants, binders, polyethylene glycol and dextran, HPMC, HPC, EC, MC, MCC, CMC, CA, etc. in an amount of about 0.1 to 50% ([0026]) in which stearic acid reads on the coating agent EC reads on binders and their amounts 0.1 to 50% overlaps the instant range of about 0.5%-about 9% of coating agent and about 0.5% to about 1.5% (instant claims 4-5: coating agent and its amount, and instant claims 6-7: binder and its amount). The implant is administered via subcutaneous route and released in a sustained release manner over a long period of time ([0024]).
It would have been obvious to optimize ingredients of DeNeui with certain amounts of Shuler to produce the claimed invention, and the desired amounts would vary depending on the intended purpose, severity of condition, etc. and thus unless criticality evidence is given, optimization is within the skill and knowledge of the ordinary artisans.
In light of the foregoing, instant clams 1-7 and 14-25 are obvious over DeNeui in view of Shuler.
Claims 8-13 are rejected under 35 USC 103 as being obvious over DeNeui et al., “Subcutaneous testosterone pellet implants – understanding the role of triamcinolone,” Evexias health solutions, 2018, pp. 1-6 (of record in application no. 18121576: PTO-892 of 03/04/2024, hereinafter “DeNeui”) in view of 26111014, “Formulation and development of fixed dose combination of artemether and lumefantrine tablets for the treatment of malaria”, 2013, The tamilanadu Dr. M.G.R. Medical University (of record in application no. 18121576: PTO-892 of 03/04/2024, and Chong et al. (US2016/0256397A1, of record in application no. 18121576: PTO-892 of 03/04/2024, hereinafter “Chong”).
DeNeui discloses implantable pellets containing about 99% testosterone, 0.04% triamcinolone, and excipients such as binder and lubricants, such as stearic acid and the pellets are released in a sustained manner for 5 months for e.g., treating adropausal hormone therapy, e.g., low level of testosterone as noted above. However, DeNeui does not expressly teach pellet hardness of no more about 75 Newtons. However, DeNeui provides pellet form of implant and pellet hardness is usually measured by e.g., compression/fracture force and thus, a skilled artisan would have had reason to optimize or adjust the compression conditions/hardness of implant containing testosterone and triamcinolone to obtain sufficient mechanical integrity for manufacture, handling, and implantation, in the absence of criticality (instant claims 8, 10, 11 and 13 (in part), and instant claims 9 and 12).
However, DeNeui does not expressly teach the steps of instant claim 8. The deficiencies are cured by 26111014 and Chong.
26111014 teaches and suggests tablet types and e.g., implant tablet containing testosterone is taught (page 10); then tablet preparation method, e.g., granulation method including wet granulation that comprises weighing the required materials including API and excipients including e.g., carrier, binder and lubricant, separately, sieving them through the sieve of appropriate pore size, mixing them to obtain the blend, adding the binder such as cellulose to the blend to obtain granules, drying the granules, adding the lubricant, and finally compressing into tablets (pages 21-23) wherein the lubricant can be used as a coating agent and includes stearate (page 18).
Chong discloses pharmaceutical formulation comprising bruton’s tyrosine kinase inhibitor and further comprise testosterone as hormones ([0676]) and triamcinolone ([0688]) and teaches the preparation method comprising (1) mixing ibrutinib with the intragranular excipients such as filler, binder, disintegrant and surfactant; (2) granulating the mixture of ibrutinib and the intragranular excipients with purified water or an aqueous binder solution under high shear granulation conditions to form granules; (3) drying the granules to form dried granules; (4) milling the dried granules; (5) blending the milled granules with the extragranular excipients such as filler, disintegrant, surfactant and lubricant; and (6) compressing the mixture of milled granules and the extragranular excipients to form tablets ([0605]) wherein the fillers in mixing step and blending step may be coating agent. The formulation is a wet granulation formulation ([0625]) (instant claims 8 and 11 – steps).
Therefore, the claimed preparation method in order to prepare a pharmaceutical composition, e.g., tablet by wet granulation e.g., mixing, granulating, drying, milling and blending would be obvious over the teachings of DeNeui in view of 2611014/Chong wherein the filler may include coating agents. In particular, DeNeui teaches a combination of testosterone, triamcinolone, stearic acid and binder. Although the applied art in combination does not expressly teach the exact claimed steps, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the preparation steps of the composition as taught by the combined teachings of Shuler in view of DeNeui and 261104 and Chong. One of ordinary skill in the art would have been motivated to do this because the claimed ingredients must be mixed to produce the final tablet composition under wet granulation method. Further, the order in which you mix them is irrelevant or insignificant, absent unexpected results. See MPEP 2144.03 IV: “See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).”
In light of the foregoing, instant claims 8-13 are obvious over DeNeui in view of 26111014 and Chong.
Claims 1-7 are rejected under 35 USC 103 as being obvious over Shuler et al. (US2006/0252049A1, of record in application 18/121576: PTO-892 of 07/19/2023, hereinafter “Shuler”) in view of Allan et al., “Testosterone deficiency in men: Diagnosis and management”, Reprinted from Australian Family Physician, vol. 32, no. 6, June 2003, pp. 422-477.
Applicant claims including the below claim 1 filed on 12/09/2024:
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Determination of the scope and content of the prior art (MPEP 2141.01);
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness Rational and Motivation (MPEP 2142-2143)
Shuler teaches an implantable pharmaceutical composition in the form of a pellet (e.g., claim 24 of prior art) for subcutaneous implantation to animal including human (e.g., [0011]) that embraces male and/or female comprising at least one bioactive agent such as triamincinolonic acetate (=triamcinolone acetate) in an amount of about 1-100% by weight of the implant, which bioactive agent reads on the claimed triamcinolone. As evidenced by US5512055A (Table 5) and US5731303A (Example 1), triamincinolone is the same as triamcinolone; and at least one pharmaceutical agent in an amount of about 50-99% such as steroid hormones, e.g., testosterone, dexamethasone, corticosteroids, prednisolone, hydrocortisone, cortisone acetate, flunisolide and triamcinolone acetate and mixtures thereof, among them, testosterone is particularly preferred steroid hormones (e.g., [0021] and claims 1- 3, 9, 11, 17, 20, 30-33, 37-39 and 49 of prior art) in which the amount of steroid hormone overlaps the instant ranges of about 90 to about 99% or about 93 to about 97% (instant claim 1, in part, and instant claim 2). Please see MPEP 2144.05(I): 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). Further Shuler teaches the composition further comprise additives, and/or excipients such as stearic acid, ethyl cellulose (=EC) and polyoxyethylene (e.g., [0025] and claim 22 of prior art), adjuvants, binders, polyethylene glycol and dextran, HPMC, HPC, EC, MC, MCC, CMC, CA, etc. in an amount of about 0.1 to 50% ([0026]) in which stearic acid reads on the coating agent EC reads on binders and their amounts 0.1 to 50% overlaps the instant range of about 0.5%-about 9% of coating agent and about 0.5% to about 1.5% (instant claims 4-5: coating agent and its amount, and instant claims 6-7: binder and its amount). The implant is administered via subcutaneous route and released in a sustained release manner over a long period of time ([0024]).
However, Shuler does not expressly teach specific combination of testosterone and trace amount of triamcinolone among various bioactive agents/pharmaceutical agents of instant claims 1 and 3. The deficiencies are cured by Allan.
Allan teaches testosterone deficiency can treated by subcutaneous insertion of implant containing testosterone pellets, intramuscular preparation, or transdermal patch wherein the testosterone and 0.05% triamcinolone can be co-administered (page 424-425).
Although Allan teaches 0.05% triamcinolone is co-administered in transdermal patch, Allan discloses triamcinolone reduces local irritation/inflammation associated with testosterone delivery. Therefore, it would have been obvious to select/add 0.05% triamcinolone of Allan to the composition of Shuler because the ordinary artisan would have been motivated to incorporate 0.05% triamcinolone into the testosterone implant of Shuler in order to reduce local inflammatory/irritative reactions associated with implantation. Therefore, incorporating 0.05% triamcinolone into known testosterone implant would have achieved the claimed invention with a reasonable expectation of success (instant claim 1).
Although Shuler and Allan do not expressly teach the amount of about 0.01 to about 0.04 of triamcinolone of instant claim 3, “about” refers to “greater than or equal to the value” according to instant publication at [0014]), and therefore, the claimed range of about 0.01 to about 0.04% reads on 0.05% of triamcinolone of Allan (instant claim 3).
In light of the foregoing, instant claims 1-7 are obvious over Shuler in view of Allan.
Claims 8-13 are rejected under 35 USC 103 as being obvious over Shuler et al. (US2006/0252049A1, of record in application 18/121576: PTO-892 of 07/19/2023, hereinafter “Shuler”) in view of Allan et al., “Testosterone deficiency in men: Diagnosis and management”, Reprinted from Australian Family Physician, vol. 32, no. 6, June 2003, pp. 422-477, and further in view of 26111014, "Formulation and development of fixed dose combination of artemether and lumefantrine tablets for the treatment of malaria", 2013, The tamilanadu Dr. M.G.R. Medical University (of record in application. no. 18/121576: PTO-892 of 07/19/2023) and Chong et al. (US2016/0256397A1, of record in application 18/121576: PTO-892 of 03/04/202), hereinafter “Chong).
Applicant claims the below claim 8 filed on 12/09/2024:
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Determination of the scope and content of the prior art (MPEP 2141.01);
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness Rational and Motivation (MPEP 2142-2143)
Shuler teaches an implantable pharmaceutical composition in the form of a pellet (e.g., claim 24 of prior art) for growth-promoting and immunizing subcutaneous implant in animal including human (e.g., [0011]); the implant comprises at least one bioactive agent such as triamincinolonic acetate (=triamcinolone acetate) in an amount of about 1-100% by weight of the implant, which bioactive agent reads on the claimed triamcinolone. As evidenced by US5512055A (Table 5) and US5731303A (Example 1), triamincinolone is the same as triamcinolone; and at least one pharmaceutical agent in an amount of about 50-99% such as steroid hormones, e.g., testosterone, dexamethasone, corticosteroids, prednisolone, hydrocortisone, cortisone acetate, flunisolide and triamcinolone acetate and mixtures thereof, among them, testosterone is particularly preferred steroid hormones (e.g., [0021] and claims 1- 3, 9, 11, 17, 20, 30-33, 37-39 and 49 of prior art), and the implant is prepared by compression ([0003] and [0032]) (instant claim 8, in part), Please see MPEP 2144.05(I): 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). Further Shuler teaches the composition further comprise additives, and/or excipients such as stearic acid, ethyl cellulose (=EC) and polyoxyethylene (e.g., [0025] and claim 22 of prior art), adjuvants, binders, polyethylene glycol and dextran, HPMC, HPC, EC, MC, MCC, CMC, CA, etc. ([0026]) in which stearic acid reads on the coating agent EC reads on binders and (instant claims 9 and 12). The implant is administered via subcutaneous route and released in a sustained release manner over a long period of time ([0024]).
However, Shuler does not expressly teach specific combination of testosterone and trace amount of triamcinolone among various bioactive agents/pharmaceutical agents of instant claim 8. The deficiencies are cured by Allan.
Allan teaches testosterone deficiency can treated by subcutaneous insertion of implant containing testosterone pellets, intramuscular preparation, or transdermal patch wherein the testosterone and 0.05% triamcinolone can be co-administered (page 424-425).
Although Allan teaches triamcinolone is co-administered in transdermal patch, triamcinolone reduces local irritation/inflammation associated with testosterone delivery. Therefore, it would have been obvious to select/add triamcinolone of Allan to the composition of Shuler because the ordinary artisan would have been motivated to incorporate triamcinolone into the testosterone implant of Shuler to reduce local inflammatory/irritative reactions associated with implantation. Thus, incorporating triamcinolone into known testosterone implant would have achieved the claimed invention with a reasonable expectation of success (instant claim 8, in part).
However, Shuler in view of Allan does not expressly teach the steps of instant
Claims 8, 10 and 11. The deficiencies are cured by 26111014 and Chong.
26111014 teaches and suggests tablet types and e.g., implant tablet containing testosterone is taught (page 10); then tablet preparation method, e.g., granulation method including wet granulation that comprises weighing the required materials including API and excipients including e.g., carrier, binder and lubricant, separately, sieving them through the sieve of appropriate pore size, mixing them to obtain the blend, adding the binder such as cellulose to the blend to obtain granules, drying the granules, adding the lubricant, and finally compressing into tablets (pages 21-23) wherein the lubricant can be used as a coating agent and includes stearate (page 18).
Chong discloses pharmaceutical formulation comprising bruton’s tyrosine kinase inhibitor and further comprise testosterone as hormones ([0676]) and triamcinolone ([0688]) and teaches the preparation method comprising (1) mixing ibrutinib with the intragranular excipients such as filler, binder, disintegrant and surfactant; (2) granulating the mixture of ibrutinib and the intragranular excipients with purified water or an aqueous binder solution under high shear granulation conditions to form granules; (3) drying the granules to form dried granules; (4) milling the dried granules; (5) blending the milled granules with the extragranular excipients such as filler, disintegrant, surfactant and lubricant; and (6) compressing the mixture of milled granules and the extragranular excipients to form tablets ([0605]) wherein the fillers in mixing step and blending step may be coating agent. The formulation is a wet granulation formulation ([0625]) (instant claims 8 and 11 – steps).
Therefore, the claimed preparation method in order to prepare an implantable pellet pharmaceutical composition, e.g., tablet by wet granulation e.g., mixing, granulating, drying, milling and blending would be obvious over the teachings of Shuler/Allan in view of 2611014/Chong wherein the filler may include coating agents. In particular, Shuler generally teaches testosterone, triamcinolone, excipients including ethyl cellulose, stearic acid, compression preparation method, and further teaches each of the agents requires different carriers, there may also be a different pellet ([0027]), and Allan teaches a combination of testosterone, triamcinolone with overlapping amounts thereof. Although the applied art in combination does not expressly teach the exact claimed steps, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the preparation steps of the composition as taught by the combined teachings of Shuler in view of DeNeui and 261104 and Chong. One of ordinary skill in the art would have been motivated to do this because the claimed ingredients must be mixed to produce the final tablet composition under wet granulation method. Further, the order in which you mix them is irrelevant or insignificant, absent unexpected results. See MPEP 2144.03 IV: “See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).”
Although the applied art does not expressly teach volatile carrier ethanol, Shuler teaches each of the agent require different carrier, and therefore selecting volatile carrier would be within the skill and knowledge of the ordinary artisan (instant claims 8, 10 and 11).
Although Shuler and Allan do not teach the pellet hardness of no more about 75 Newtons, the applied references both provide pellet form and pellet hardness is measured by compression/fracture force and thus, a skilled artisan would have had reason to optimize or adjust the compression conditions/hardness of implant containing testosterone and triamcinolone to obtain sufficient mechanical integrity for manufacture, handling, and implantation, in the absence of criticality (instant claim 13).
In light of the foregoing, instant claims 8-13 are obvious over Shuler in view of Allan and further in view of 26111014/Chong.
Claims 14-25 are rejected under 35 USC 103 as being obvious over Shuler et al. (US2006/0252049A1, of record in application 18/121576: see PTO-892 of 07/19/2023, hereinafter “Shuler”) in view of Allan et al., “Testosterone deficiency in men: Diagnosis and management”, Reprinted from Australian Family Physician, vol. 32, no. 6, June 2003, pp. 422-477, and further in view of Cavender et al., “Subcutaneous Testosterone pellet implant (Testopel®) therapy for men with testosterone deficiency syndrome: a single-site retrospective safety analysis,” International Society for Sexual Medicine, 2009:6:3177-3192 (IDS of 04/27/2022 in application 17/730305, hereinafter “Cavender”).
Applicant claims the below claims 14 and 20 filed on 12/09/2024:
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Determination of the scope and content of the prior art (MPEP 2141.01);
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02); and Finding of prima facie obviousness Rational and Motivation (MPEP 2142-2143)
Shuler teaches an implantable pharmaceutical composition in the form of a pellet (e.g., claim 24 of prior art) for growth-promoting and immunizing subcutaneous implant in animal including human (e.g., [0011]) that embraces male and/or female, and please note that growth-promoting correlate to improve testosterone deficiency because the deficiency leads to reduced overall body growth, lower muscle mass, and decreased weight gain and testosterone is an anabolic hormone that promotes protein synthesis and nitrogen retention in skeletal muscle; the implant comprises at least one bioactive agent such as triamincinolonic acetate (=triamcinolone acetate) in an amount of about 1-100% by weight of the implant, which bioactive agent reads on the claimed triamcinolone. As evidenced by US5512055A (Table 5) and US5731303A (Example 1), ‘triamincinolone’ is the same as ‘triamcinolone’; and at least one pharmaceutical agent in an amount of about 50-99% such as steroid hormones, e.g., testosterone, dexamethasone, corticosteroids, prednisolone, hydrocortisone, cortisone acetate, flunisolide and triamcinolone acetate and mixtures thereof, among them, testosterone is particularly preferred steroid hormones (e.g., [0021] and claims 1- 3, 9, 11, 17, 20, 30-33, 37-39 and 49 of prior art) in which the amount of steroid hormone overlaps the instant ranges of about 90 to about 99% (instant claims 14, 16 and 20, in part, and instant claims 15, 21 and 23-24), Please see MPEP 2144.05(I): 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). Further Shuler teaches the composition further comprise additives, and/or excipients such as stearic acid, ethyl cellulose (=EC) and polyoxyethylene (e.g., [0025] and claim 22 of prior art), adjuvants, binders, polyethylene glycol and dextran, HPMC, HPC, EC, MC, MCC, CMC, CA, etc. ([0026]) in which stearic acid reads on the coating agent EC reads on binders and (instant claims 17-18 and 22). The implant is administered via subcutaneous route and released in a sustained release manner over a long period of time ([0024]).
However, Shuler does not expressly teach specific combination of testosterone and trace amount of triamcinolone among various bioactive agents/pharmaceutical agents of instant claims 14, 16 and 20. The deficiencies are cured by Allan.
Allan teaches testosterone deficiency can treated by subcutaneous insertion of implant containing testosterone pellets, intramuscular preparation, or transdermal patch wherein the testosterone and 0.05% triamcinolone can be co-administered (page 424-425).
Although Allan teaches 0.05% triamcinolone is co-administered in transdermal patch, it is taught that triamcinolone reduces local irritation/inflammation associated with testosterone delivery. Therefore, it would have been obvious to select/add 0.05% triamcinolone of Allan to the composition of Shuler because the ordinary artisan would have been motivated to incorporate 0.05% triamcinolone into the testosterone implant of Shuler to reduce local inflammatory/irritative reactions associated with implantation, as taught by Allan. That is, incorporating 0.05%triamcinolone into known testosterone implant would have achieved the claimed invention with a reasonable expectation of success (instant claims 14, 16 and 20).
Although Shuler and Allan do not teach the pellet hardness of no more about 75 Newtons, the applied references both provide pellet form and pellet hardness is usually measured by compression/fracture force and thus, a skilled artisan would have had reason to optimize or adjust the compression conditions/hardness of implant containing testosterone and triamcinolone to obtain sufficient mechanical integrity for manufacture, handling, and implantation, in the absence of criticality. (instant claims 14 and 21).
However, Shuler and Allan do not expressly teach sustained release period of instant claims 19 and 25. The deficiency is cured by Cavender.
Cavender teaches long-acting subcutaneous testosterone pellet implant (Testopel®) for men with testosterone deficiency syndrome provides sustained and steady testosterone levels for 3 to 6 months which overlaps the instant range of 4 to 6 months for the treatment of men with testosterone deficiency syndrome (abstract) wherein the testosterone is used in an amount of 75mg (Testopel®) or 200mg (Testosterone implant) (page 3178). Cavender further teaches the pellet implant may give the patient experience of side effects e.g., redness and swelling at the implant site (page 3192). As evidenced by Endo Pharmaceuticals, Inc. (IDS of 04/27/2022 in application 17/730305), Testopel® contains 75mg testosterone, NF 0.97mg stearic acid which is within the claimed range of about 0.4 to about 12 mg and USP 2mg PVP (page 2).
Shuler/Cavender teach sustained release, and in particular, Cavender teaches the implant is released over 4 to 6 months, and thus it would have been obvious to keep drug levels steady in the blood, prevent high toxic peaks, avoids low ineffective drops, and less often taking implant.
In light of the foregoing, instant claims 14-25 are obvious over Shuler in view of Allan and further in view of Cavender.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-7 and 14-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of patent 11,628,138B in view of Shuler and/or DeNeui.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets require implantable pharmaceutical composition comprising testosterone, triamcinolone and excipients, with their amounts. The difference between them is both inventions use different units, and instant invention further requires pellet form and its hardness. However, such differences would not make two inventions distinct over each other, because hormone therapy implants are generally made of small, solid type pf tiny pellets, as taught by Shuler and/or DeNeui (see entire documents).
Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patent ‘138 subject matter.
Claims 8-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of patent 12,161,751B in view of Shuler.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets require process of making implantable pharmaceutical composition comprising the steps of combining the ingredients, adding binder ethylcellulose in volatile carrier to form wet granules, drying wet granules to form bulk granules, milling. The difference between them is that instant claim require compressing step to form pellets, and however, such compression step in granulation process is obvious as taught by Shuler ([0032]).
Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patent ‘751 subject matter.
Conclusion
All the claims examined are rejected.
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/KYUNG S CHANG/Primary Examiner, Art Unit 1613
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