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 .
Election/Restrictions
Applicant’s election without traverse of Group (I) with the addition osteoarthritis as the elected subject suffering from a disease species and the inflammation or pain species, knees, and solution as the dosage form in the reply filed on 11/03/2025 is acknowledged.
Claims 7-12 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
This application is the U.S. national stage application, under 35 U.S.C. § 371, of
International Patent Application No. PCT/CN2021/098323, filed on June 4, 2021, which claims the benefit and priority of International Patent Application No. PCT/CN2020/094560, filed on June 5, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/09/2023 & 11/17/2025 has been considered by the examiner.
Claim Status
Claims 4-12, 14-16, and 18-30 are pending. Claims 1-3, 13, and 17 are canceled. Claims 7-12 are withdrawn. Claims 4-6, 14-16, and 18-30 are examined in accordance to the elected species.
Claim Rejections - 35 USC § 112
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 the applicant regards as his invention.
Claims 14-16, and 21-27, and 30 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 11, 14-16, and 21-27, and 30, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 14 recites the broad recitation the dosage form of claim 10, selected from the group consisting of an alcohol solution, an acetone solution, a dimethyl sulfoxide solution, an alcohol-water solution, an acetone-water solution, and a dimethyl sulfoxide-water solution, and the claim also recites preferably an ethanol-water solution, preferably a 10% to 50% (v/v) ethanol-water solution, particularly a 25% (v/v) ethanol water solution. which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 14 recites the broad recitation wherein 2- (diethylamino)ethyl 2-(4-isobutylphenyl) propionate, or a pharmaceutically acceptable salt thereof, is topically administered in an amount of about 0.5 mg to about 64 mg, and the claim also recites particularly about 8 mg to about 16 mg, or particularly about 16 mg to about 32 mg, or particularly about 32 mg to about 64 mg, per day per site which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 15 recites the broad recitation wherein 2- (diethyl amino)ethyl 2-(4-isobutylphenyl)propionate, or a pharmaceutically acceptable salt thereof, is topically administered in an amount of about 8 mg to about 64 mg, and the claim also recites particularly about 4 mg to about 8 mg, or particularly about 8 mg to about 16 mg, or particularly about 16 mg to about 32 mg, per dose per site which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 16 recites the broad recitation wherein 2- (diethylamino)ethyl 2-(4-isobutylphenyl)propionate, or a pharmaceutically acceptable salt thereof, is topically administered in an amount of about 30 µg/cm2 to about 480 µg/cm2, and the claim also recites particularly about 30 µg/cm2 to about 60 µg/cm2, particularly about 60 µg/cm2 to about 120 µg/cm2, or particularly about 120 µg/cm2 to about 240 µg/cm2, or particularly about 240 µg/cm2 to about 480 µg/cm2, per dose per site which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 21 recites the broad recitation wherein 2- (diethylamino)ethyl 2-(4-isobutylphenyl) propionate, or a pharmaceutically acceptable salt thereof, is topically administered to one or more surfaces of the site, and the claim also recites in particular topically administered to the medial surface, the lateral surface, the front surface and/or the back surface of the site, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 22 recites the broad recitation wherein 2- (diethyl amino)ethyl 2-(4-isobutylphenyl)propionate is topically administered in a dosage form selected from the group consisting of an alcohol solution, an acetone solution, a dimethyl sulfoxide solution, an alcohol water solution, an acetone water solution, or a dimethyl sulfoxide water solution, and the claim also recites in particular from transdermal drops, rinces or spray, in particular spray which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 23 recites the broad recitation wherein 2- (diethyl amino)ethyl 2-(4-isobutylphenyl)propionate is topically administered in a dosage form selected from the group consisting of an alcohol solution, an acetone solution, a dimethyl sulfoxide solution, an alcohol water solution, an acetone water solution, or a dimethyl sulfoxide water solution, and the claim also recites preferably an ethanol water solution, more preferably 10% to 50% (v/v) ethanol-water solution, particularly 25% (v/v) ethanol-water solution which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 24 recites the broad wherein the 2- (diethylamino)ethyl 2-(4-isobutylphenyl)propionate, or a pharmaceutically acceptable salt thereof, is administered to the subject as a solution having a concentration of about 10 mg/mL to about 200 mg/m, and the claim also recites preferably about 30 mg/mL to about 100 mg/mL, more preferably about 50mg/mL to about 80 mg/mL, particularly about 70 mg/mL which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 25 recites the broad recitation wherein the 2- (diethylamino)ethyl 2-(4-isobutylphenyl)propionate, or a pharmaceutically acceptable salt thereof, is topically administered to the subject in a unit dose of about 0.01 mL to about 1 mL, and the claim also recites particularly about 0.03 mL to about 0.3 mL, particularly about 0.04 mL to about 0.2 mL, particularly about 0.05 mL to about 0.1 mL, particularly about 0.07 mL which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 26 recites the broad recitation wherein the 2- (diethylamino)ethyl 2-(4-isobutylphenyl) propionate or pharmaceutically acceptable salt thereof is administered in an amount of about 0.1 mg to about 8 mg, and the claim also recites particularly about 2 mg to about 6 mg, particularly about 3 mg to about 5 mg, particularly about 4 mg to about 4.75 mg, particularly about 4.5 mg, per unit dose which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 27 recites the broad recitation wherein one or more unit doses comprising a composition comprising 2-(4-isobutylphenyl)propionate, or a pharmaceutically acceptable salt thereof, is topically administered to the subject in a single dose per site; and wherein said one or more unit doses are 1-20 unit doses, and the claim also recites particularly 1-10 unit doses, particularly 1-5 unit doses, particularly 2-4 unit doses, particularly 2-3 unit doses, or particularly I unit dose, or particularly 2 unit doses, or particularly 4 unit doses, or particularly 8 unit doses which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 27 recites the broad recitation wherein the 2- (diethyl amino) ethyl 2-(4-isobutylphenyl) propionate or pharmaceutically acceptable salt thereof is administered for1 day to life time, and the claim also recites particularly 7 to 365, 14 to 91, 14 to 84, 28 to 84, or 56 to 84 consecutive or non-consecutive days, particularly consecutive days which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 4-6, 14-16, and 18-30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a subject suffering pain or inflammation by topically administrating 2-(diethylamino) ethyl 2-(4-isobutylphenyl) propionate, or a pharmaceutically acceptable salt thereof, does not reasonably provide enablement for treating a subject at risk of suffering from or potentially capable of suffering from pain or inflammation by topically administrating 2-(diethylamino) ethyl 2-(4-isobutylphenyl) propionate, or a pharmaceutically acceptable salt thereof The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are several guidelines when determining if the specification of an application allows the skilled artisan to practice the invention without undue experimentation. The factors to be considered in determining what constitutes undue experimentation were affirmed by the court in re Wands (8 USPQ2d 1400 (CAFC 1986)). These factors are (1) nature of the invention; (2) state of the prior art; (3) level of one of ordinary skill in the art; (4) level of predictability in the art; (5) amount of direction and guidance provided by the inventor; (6) existence of working examples; (7) breadth of claims; and (8) quantity of experimentation needed to make or use the invention based on the content of the disclosure.
(1) Nature of the invention
The claims are directed to treatment of a subject suffering from, at risk of suffering from, or potentially capable of suffering from a pain or inflammation.
(2) State of the prior art
The state of the art is that 2-(diethylamino) ethyl 2-(4-isobutylphenyl) propionate can be effective to treat a subject suffering from pain or inflammation. (Yu et al (US9,872,846 B2). of the obviousness below). Thus, one cannot ascertain whether the instant invention is of use of the claimed compound in a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation can be predicted to treat pain or inflammation.
(3) Level of one of ordinary skill in the art
The level of skill in the art is deemed to be high, generally that of a medical Doctor specializing in the field of pain management.
(4) Level of predictability in the art
The art pertaining to the use of the claimed compound in a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation is highly unpredictable. Specifically, namely Cleveland Clinic (Health Essentials, August 25, 2025) teaches ibuprofen can interact with other medicines, especially, high blood pressure medications, which can lead to some serious side effects, which could be deadly. (See Can other medication interact with ibuprofen? Section.) Cleveland Clinic also teaches to avoid ibuprofen with certain conditions such as heart issues, gastrointestinal problems (heartburn), and kidney problems. (See Should you avoid ibuprofen with certain conditions? Section.) Furthermore, Cleveland Clinic teaches ibuprofen should not be viewed as a cure-all for anything that ails you — or what might ail you. “It shouldn’t be used to try to ward off problems in advance,” (See How to take ibuprofen responsibly Section.)
Meyers (Certified June 2018) teaches avoid NSAIDs, especially ibuprofen and naproxen, for several weeks following surgery. In my mind, surgery causes inflammation, so NSAIDs would be the natural choice. On the contrary, as my doctor explained, NSAIDS have actually been linked to delayed healing times. Prolonged NSAID use lengthens recovery time, due to inhibiting prostaglandin production. Research suggests that this is true regarding healing from acute injury to bone, muscles, ligaments and tendons. What about preventing injury? Many athletes and exercisers take NSAIDs prophylactically to prevent muscle soreness and muscle damage and improve performance. But studies suggest that this is a waste of money—and may even be doing more damage. (See Do NSAIDs actually cause inflammation Section.)
In sum, a person of ordinary skill in the art would not expect that compounds with similar core to ibuprofen such as the compound taught by Yu or by the claimed compound cannot be expected to be beneficial for a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation where said subject can be a subject that just had surgery, a subject with heart issues, gastrointestinal problems (heartburn), and kidney problems, or a healthy subject with preexisting conditions.
(5) Amount of direction and guidance provided by the inventor
The claims encompass a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation. Applicant’s limited guidance does not enable the public to use of the claimed compound of the formula (I) in a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation There is no directional guidance for the use of the claimed compound in a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation. Hence, there is no enablement for a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation.
(6) Existence of working examples
The claims encompass a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation that lacks the utility. Applicant’s limited working examples do not enable the public to use of the claimed compound in a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation. While Applicant’s claims encompass a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation the specification only provides guidance of the claimed compound in a subject suffering from a pain or an inflammation.
(7) Breadth of claims
The claims are extremely broad due to a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation that can encompass a subject that just had surgery, a subject with heart issues, gastrointestinal problems (heartburn), and kidney problems, or a healthy subject with preexisting conditions.
(8) Quantity of experimentation needed to make or use the invention based on the content of the disclosure
The specification does not enable any person skilled in the art to which it pertains to make and use the invention commensurate in scope with the claims because the claimed compound (an ibuprofen derivative) is not expected to be used in a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation. In particular, the specification fails to enable the skilled artisan to practice the invention without undue experimentation to use of the claimed compound in a subject at risk of suffering from, or potentially capable of suffering from a pain or inflammation. Furthermore, based on the unpredictable nature of the invention, the state of the prior art, and the extreme breadth of the claims, one skilled in the art could not perform the claimed invention without undue experimentation
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.
Claims 4-6, 14-16, 18, 20, and 22-30 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al (US9,872,846 B2).
Yu teaches a method for treating an ibuprofen-treatable condition in a subject in need thereof comprising:
transdermally administering to the subject a pharmaceutical composition,
wherein the ibuprofen-treatable condition is selected from fever, pain, and inflammation; and
wherein the pharmaceutical composition comprises a therapeutically effective amount of at least one compound of Structure 1:
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or stereoisomers thereof. (See claim 10) Moreover, Yu teaches the condition treatable by Ibuprofen is rheumatoid arthritis or osteoarthritis and the composition is formulated as a solution, suspension, spray, lotion, emulsion or a gel, and the subject is a human subject. (See claims 2-6.) The compound is
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. (See claim 10.) This compound is the same as the compound claimed. Yu teaches a typical pharmaceutical composition for intravenous administration would be from about 0.01 mg, up to about 5 g, per subject per day may be used. (See lines 34-39 of column 76.) 0.01 to 5 g amount to 10 mg to 5000 mg. Yu also teaches the pharmaceutically acceptable carrier is an aqueous carrier, e.g. buffered saline and the like. In certain embodiments, the pharmaceutically acceptable carrier is a polar solvent, e.g. acetone and alcohol. (See lines 14-17 of column 76.) Yu teaches topical application of 1 ml of a 20% suspension of 2-(ρ-isobutylphenyl) propionic acid (IBPP) or 20% solution of diethylaminoethyl 2-(ρ-isobutylphenyl) propionate.AcOH (DEAE-IBPP) to the backs of hairless mice. (See Figure 2C.) For a ml volume solution and 10 mg of the compound, a 10 mg/ml can be obtained. For a 1 mL of 20% solution containing ethanol. Density of ethanol is 0.789 g/ml. So, a 1 ml sample of a 20% solution can contain 0.2 ml solute and approx. 0.8 mg of solvent. Mass of solute = 0.2 ml X 0.789 g/ml = 0.1578 g.
Converting grams to micrograms (µg): 0.1578 g X 1, 000, 000 µg/g = 157.800 µg
Determining the concentration in µg/ml: 157.800 µg / 1 ml = 157.800 µg/ml. Yu teaches 20% aqueous acetone solution was used. (See line 4 of column 144.) Furthermore, Yu teaches the penetration rate of the prodrug compounds such as diethylaminoethyl 2-(p-isobutylphenyl) propionate, ACOH contains 50 µg/cm2. (See Table 2 of column 117-118.) Yu teaches thee pharmaceutical compositions can be administered in a variety of unit dosage forms depending upon the method of administration. (See lines 29-30 of column 76.) Daily administration encompasses once every 24 hours and 1 day. Lastly, Yu teaches the HPP or the active ingredient can be administered systematically (e.g. orally or parenterally). The HPP or the active agent (e.g., drug or metabolite) of the HPP may enter the general circulation with a faster rate than the parent agent and gain faster access to the action site a condition. (See lines 42-47 of column 87,) The lowest detectable penetration across the skin the rat is 1 µg/cm2 for the parent drug. However, a higher apparent flux values for the HPPs. (See lines 56-67 of column 116.)
Yu does not specifically teach an amount of about 1 mg to about 80 mg per day per site (claim 4) and amount of 5 µg/cm2 to about 2 mg/cm2 (claim 6).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by Yu by administering the compound of claim 10 in an amount of about 1 mg to about 80 mg per day per site (claim 4) or amount of 5 µg/cm2 to about 2 mg/cm2 per dose per site to give Applicant’s claimed method. One would have been motivated to do so, because Yu teaches typical pharmaceutical composition for intravenous administration would be from about 0.01 mg, up to about 5 g, per subject per day may be used, which can be converted to 0.01 to 5 g amount to 10 mg to 5000 mg and also teaches a 1 mL of 20% solution containing aqueous ethanol that can be administered in a variety of unit dosage forms with a detectable penetration flux of the parent ibuprofen in the amount 1250 µg/cm2 and penetration rate of the prodrug compounds such as diethylaminoethyl 2-(p-isobutylphenyl) propionate, ACOH contains 50 µg/cm2. The 1250 µg/cm2 can be converted to 1.25 mg/cm2. One would reasonably expect the inclusion of the amount of 1.25 mg/cm2 or 10 mg per dose per site to treat osteoarthritis with success.
Claims 4-6, 14-16, 18, 19, 20, 21, 22, and 22-30 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al (US9,872,846 B2) as applied to claims 4-6, 14-16, 18, 20, and 22-30 in view of Argoff et al (Ther Clin Risk Manag. 2011 Sep 20; 7:393–399.)
The teachings of Yu have been discussed in the above rejection.
Argoff teaches topical NSAIDs have shown efficacy and safety in knee (DSG, D-DMSO) and hand (DSG) osteoarthritis. topical NSAIDs can ease medication administration and help address barriers to pain management in older patients with osteoarthritis, such as taking multiple medications and inability to swallow, and are a valuable option for long-term care providers. (See Abstract.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by Yu by including any area or surface of the knees to treat osteoarthritis. One would have been motivated to do so, because Argoff teaches topical NSAIDs have shown efficacy and safety in knee (DSG, D-DMSO) and hand (DSG) osteoarthritis and the compound of claim 10 pf Yu is a prodrug of ibuprofen and NDSAID. One would reasonably expect the method taught by Yu to successfully the osteoarthritis of the knees by topically apply compound 10 to every area or surface that include the surface of claim 21.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 4-6, 14-16, and 18-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9,872,846 B2 in view of Yu et al (US9,872,846 B2) and Argoff et al (Ther Clin Risk Manag. 2011 Sep 20; 7:393–399.). Although the claims at issue are not identical, they are not patentably distinct from each other.
The U.S. patent claims teach a method for treating an ibuprofen-treatable condition in a subject in need thereof comprising:
transdermally administering to the subject a pharmaceutical composition,
wherein the ibuprofen-treatable condition is selected from fever, pain, and inflammation; and
wherein the pharmaceutical composition comprises a therapeutically effective amount of at least one compound of Structure 1:
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or stereoisomers thereof. (See claim 10) Moreover, the U.S. patent claims teach the condition treatable by Ibuprofen is rheumatoid arthritis or osteoarthritis and the composition is formulated as a solution, suspension, spray, lotion, emulsion or a gel, and the subject is a human subject. (See claims 2-6.) The compound is
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. (See claim 10.) This compound is the same as the compound claimed.
The U.S. patent claims do not teach the amount of the compound claimed in mg per day per site and in µg/cm2. The U.S. patent claims do not teach the knees as one or more surfaces of the administration site.
Yu teaches a method for treating an ibuprofen-treatable condition in a subject in need thereof comprising:
transdermally administering to the subject a pharmaceutical composition,
wherein the ibuprofen-treatable condition is selected from fever, pain, and inflammation; and
wherein the pharmaceutical composition comprises a therapeutically effective amount of at least one compound of Structure 1:
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or stereoisomers thereof. (See claim 10) Moreover, Yu teaches the condition treatable by Ibuprofen is rheumatoid arthritis or osteoarthritis and the composition is formulated as a solution, suspension, spray, lotion, emulsion or a gel, and the subject is a human subject. (See claims 2-6.) The compound is
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. (See claim 10.) This compound is the same as the compound claimed. Yu teaches a typical pharmaceutical composition for intravenous administration would be from about 0.01 mg, up to about 5 g, per subject per day may be used. (See lines 34-39 of column 76.) 0.01 to 5 g amount to 10 mg to 5000 mg. Yu also teaches the pharmaceutically acceptable carrier is an aqueous carrier, e.g. buffered saline and the like. In certain embodiments, the pharmaceutically acceptable carrier is a polar solvent, e.g. acetone and alcohol. (See lines 14-17 of column 76.) Yu teaches topical application of 1 ml of a 20% suspension of 2-(ρ-isobutylphenyl) propionic acid (IBPP) or 20% solution of diethylaminoethyl 2-(ρ-isobutylphenyl) propionate.AcOH (DEAE-IBPP) to the backs of hairless mice. (See Figure 2C.) For a ml volume solution and 10 mg of the compound, a 10 mg/ml can be obtained. For a 1 mL of 20% solution containing ethanol. Density of ethanol is 0.789 g/ml. So, a 1 ml sample of a 20% solution can contain 0.2 ml solute and approx. 0.8 mg of solvent. Mass of solute = 0.2 ml X 0.789 g/ml = 0.1578 g.
Converting grams to micrograms (µg): 0.1578 g X 1, 000, 000 µg/g = 157.800 µg
Determining the concentration in µg/ml: 157.800 µg / 1 ml = 157.800 µg/ml. Yu teaches 20% aqueous acetone solution was used. (See line 4 of column 144.) Furthermore, Yu teaches the penetration rate of the prodrug compounds such as diethylaminoethyl 2-(p-isobutylphenyl) propionate, ACOH contains 50 µg/cm2. (See Table 2 of column 117-118.) Yu teaches thee pharmaceutical compositions can be administered in a variety of unit dosage forms depending upon the method of administration. (See lines 29-30 of column 76.) Daily administration encompasses once every 24 hours and 1 day. Lastly, Yu teaches the HPP or the active ingredient can be administered systematically (e.g. orally or parenterally). The HPP or the active agent (e.g., drug or metabolite) of the HPP may enter the general circulation with a faster rate than the parent agent and gain faster access to the action site a condition. (See lines 42-47 of column 87,) The lowest detectable penetration across the skin the rat is 1 µg/cm2 for the parent drug. However, a higher apparent flux values for the HPPs. (See lines 56-67 of column 116.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by the U.S. patent claims by administering the compound of claim 10 in an amount of about 1 mg to about 80 mg per day per site (claim 4) or amount of 5 µg/cm2 to about 2 mg/cm2 per dose per site to give Applicant’s claimed method. One would have been motivated to do so, because Yu teaches typical pharmaceutical composition for intravenous administration would be from about 0.01 mg, up to about 5 g, per subject per day may be used, which can be converted to 0.01 to 5 g amount to 10 mg to 5000 mg and also teaches a 1 mL of 20% solution containing aqueous ethanol that can be administered in a variety of unit dosage forms with a detectable penetration flux of the parent ibuprofen in the amount 1250 µg/cm2 and penetration rate of the prodrug compounds such as diethylaminoethyl 2-(p-isobutylphenyl) propionate, ACOH contains 50 µg/cm2. The 1250 µg/cm2 can be converted to 1.25 mg/cm2. One would reasonably expect the inclusion of the amount of 1.25 mg/cm2 or 10 mg per dose per site to treat osteoarthritis with success.
Argoff teaches topical NSAIDs have shown efficacy and safety in knee (DSG, D-DMSO) and hand (DSG) osteoarthritis. topical NSAIDs can ease medication administration and help address barriers to pain management in older patients with osteoarthritis, such as taking multiple medications and inability to swallow, and are a valuable option for long-term care providers. (See Abstract.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by the U.S. patent claims by including any area or surface of the knees to treat osteoarthritis. One would have been motivated to do so, because Argoff teaches topical NSAIDs have shown efficacy and safety in knee (DSG, D-DMSO) and hand (DSG) osteoarthritis and the compound of claim 10 pf Yu is a prodrug of ibuprofen and NDSAID. One would reasonably expect the method taught by the U.S. patent claims to successfully the osteoarthritis of the knees by topically apply compound 10 to every area or surface that include the surface of claimed.
Conclusion
Claims 4-6, 14-16, and 18-30 are not allowed.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628