DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on October 31, 2025 has been entered.
Claims 1 , 3-17 are currently pending and are examined on the merits herein.
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 .
Application Priority
This application filed 07/18/2021 is a DIV of PAT 11110077 filed on 09/26/2018 and a national stage entry of PCT/IN2016/000237 , International Filing Date: 09/30/2016, claims foreign priority to INDIA 201641011015, filed 03/30/2016.
Information Disclosure Statement
No new information disclosure statement(s) (IDS) has been filed.
Status of the Claims
Claims 1, 3-17, are currently pending and are examined on the merits herein.
Response to Arguments
Applicant’s arguments over the 35 U.S.C. 112 rejection is persuasive due to amendments made to the claims. The rejection is herewith withdrawn.
Applicant’s arguments over the 35 U.S.C. 103 rejection of claims 1, 3-12 over Muller et al. (US20060183787) is not persuasive. The rejection is herewith maintained. Muller discloses a concentration of DMSO of 0.25% in all samples and this reads on the claimed amount of claims 1 and 6. However, independent claim 1 currently requires "a pharmaceutically acceptable carrier at a concentration range of 5-30% w/w." In this regard, the minimum amount of the "pharmaceutically acceptable carrier" required in the pharmaceutical composition for topical administration is 5% w/w. As a result, Applicant respectfully submits that the Office Action has failed to reasonably conclude how a final DMSO concentration of 0.25% as allegedly disclosed in Example 8 reads on the weight percentage feature with respect to the "pharmaceutically acceptable carrier" as required by independent claim 1.
In response, the Examiner remind Applicant the total amount of carrier in the prior art is not 0.25%, but moreover, Applicant’s independent claims do not require any DMSO. Of note, the Examiner attempted to contact Applicant on multiple occasions but was unsuccessful. The Examiner request Applicant call.
Applicant’s arguments over the 35 U.S.C. 103 rejection of claims 13-17 over Zeldis et al (US 2007/0155791 A1) and further in view of Chang et al (The AAPS Journal, 2012; 15(1):41-52) is persuasive. The rejection is herewith withdrawn.
Applicant will submit a T.D. upon an allowance.
The rejection is as below:
Claim Rejections - 35 USC § 112
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 1 and 3 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 of psoriasis, does not reasonably provide enablement for any inflammatory disease or disorder. 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.
The instant claims are drawn to a method of treating inflammatory disease or disorder in a subject by the method comprising topically administering a pharmaceutical composition to an affected skin of the subject for a period of time until symptoms of the inflammatory disease or disorder are abated, the pharmaceutical composition comprising 0.5-10% w/w of apremilast or its pharmaceutically acceptable salt; a pharmaceutically acceptable carrier at a concentration range of 5- 30% w/w; and a pharmaceutically acceptable excipient; wherein the a ratio of apremilast or its pharmaceutically acceptable salt to the pharmaceutically acceptable carrier is in the range of 1:100 to 100:1; wherein the a pH of the pharmaceutical composition ranges from 3 to 8.
The instant specification fails to provide information that would allow the skilled artisan to practice the treatment of inflammatory disease or disorder”. with said formulation.
[In re Sichert, 196 USPQ 209 (CCPA 1977)]
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).1
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative
skill level
The invention relates to a method of treating any inflammatory disease comprising administering to a subject, The relative skill of those in the art is high, that of an MD or PHD. That factor is outweighed, however, by the unpredictable nature of the art. As illustrative of the state of the art, the examiner cites the fact that while Applicant demonstrated the stability of the formulations, nowhere in the specification did applicant demonstrate the use of said the formulation in treating inflammatory disease or disorder in a subject as contemplated by the recitation in claim 1. Importantly, the examiner contends that treating inflammatory disease or disorder in a subject encompasses various conditions and yet applicant failed to provide enablement for any inflammatory disease or disorder in a subject utilizing the formulation. Further, the predictability of treating any inflammatory disease or disorder with the formulation is relatively low. Thus, given that applicant has failed to demonstrate treatment of all inflammatory diseases or disorder s utilizing the formulation and in light of the challenge in treating all inflammatory disease or disorder with the formulation, the examiner maintains that applicant has not enabled the breadth of the claims.
2. The breadth of the claims
The claims are thus very broad insofar as they recite the “treatment of inflammatory disease or disorder”. While such “treatment” might theoretically be possible for treating some inflammatory disease or disorder utilizing formulation, as a practical matter it is nearly impossible to achieve a treatment for all inflammatory disease or disorder with the formulation.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides no direction or guidance for the use of any of the formulations in treating any inflammatory disease or disorder. No reasonably specific guidance is provided concerning useful therapeutic protocols for the formualtion.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the formulation could be predictably used for the treatment of all inflammatory disease or disorder as inferred by the claims and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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.
Claims 1, 3-12 are rejected under 35 U.S.C. 103 as being unpatentable over Muller et al. (US20060183787).
Muller et al. teaches a method of treating psoriatic arthritis in humans in need thereof, which comprises administering to a patient in need of such treatment a therapeutically effective amount of (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione (aka Apremilast). (See abstract, claim 1 [0010]) Exemplified for culturing, compounds of (+) isomer and racemate were dissolved in DMSO (Sigma) and further dilutions were done in culture medium immediately before use. The final DMSO concentration in all samples was 0.25%. (reads on the claimed amount and ratio of claims 1 and 6) [0128] Drugs can be applied locally to the skin and its adnexa or to a variety of mucous membranes. [0089] Suitable excipients (e.g., carriers and diluents) and other materials that can be used to provide topical and mucosal dosage forms. . Non-limiting examples of typical excipients include water, acetone, ethanol, ethylene glycol, propylene glycol, butane-1,3-diol, isopropyl myristate, isopropyl palmitate, mineral oil and mixtures thereof to form solutions, emulsions or gels, which are non-toxic and pharmaceutically acceptable. [0090] Non-limiting examples of occlusives include petrolatum, lanolin, mineral oil, silicones such as dimethicone, zinc oxide and combinations thereof. [0093] Non-limiting examples of humectants include glycerin, sorbitol, urea, alpha hydroxy acids, sugars and combinations thereof. [0093] The pH of a pharmaceutical composition or dosage form may also be adjusted to improve delivery of one or more active ingredients. Similarly, the polarity of a solvent carrier, its ionic strength or tonicity can be adjusted to improve delivery. [0096] Example 10 discusses Aqueous Solibility and teaches equilibrium solubility was measured in pH 7.4 aqueous buffer. The pH 7.4 buffer was prepared by adjusting the pH of a 0.07 M NaH2PO4 solution to 7.4 with 10 N NaOH. [0131] Stearates can serve as a lipid vehicle for the formulation, as an emulsifying agent or surfactant and as a delivery-enhancing or penetration-enhancing agent. [0096] “stabilizers,” include, but are not limited to, antioxidants [0067] Vitamin E is a common additive, which appears to have no effect, except as an emollient [0094]
However, Muller et al. does not specifically mention the use of 0.5-10% of apremilast or the ratio to carrier in claim 1.
From the teachings of Muller et al., one of ordinary skill in the art would have found it obvious to arrive at the instant claim 1. The determination of optimal or workable amounts by routine experimentation is obvious. One having ordinary skill in the art would have been motivated to modify the amounts of apremilast, because Muller et al. teaches the composition, shape and type of dosage forms will typically vary depending on their use. For example, a dosage form used in the acute treatment of a disease may contain larger amounts of one or more of the active ingredients it comprises than a dosage form used in the chronic treatment of the same disease. These and other ways in which specific dosage forms will vary from one another will be readily apparent to those skilled in the art [0088]. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 35 of US Applic. No. 16481257.
The reference claim 35 of ‘257 are to:
A method of treating psoriasis or psoriasis arthritis related disorders by
administering a topical pharmaceutical composition comprising:
a. 2-4% w/w of apremilast or a pharmaceutically acceptable salt thereof,
b. 1-30% w/w of an emollient,
C. 1-50% w/w of a carrier,
d. 1-10% w/w of an emulsifier,
e. 0.001-15% w/w of a penetration enhancer, and
f. preservatives and solvent,
while the claims herein are drawn to a method of treating inflammatory disease or disorder in a subject by topically administering a pharmaceutical composition comprising 0.5-10% of apremilast or its pharmaceutically acceptable salt by topically applying the composition to the affected skin of the subject for a period of time till the symptoms of psoriasis are abated.
Conclusion
No claims allowed.
The arguments are not persuasive and the rejection is made FINAL.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAYLA SOROUSH whose telephone number is (571)272-5008. The examiner can normally be reached on Monday thru Friday; 8:30 AM to 5:00 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, James Henry Alstrum-Acevedo, can be reached on (571)272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAYLA SOROUSH/ Primary Examiner, Art Unit 1622
1 As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.