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 .
Claims 1-6 and 18-20 are presented for examination.
The amendments and remarks filed on12/01/2025 have been received and entered.
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 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.
Claim(s) 1-6 and 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Matsuda (US
20190247369) in view of Wang et al. (WO 20182087) and further in view of Ghate et al. ( Utility of
Sulfobutyl Ether ß-Cyclodextrin Inclusion Complexes in Drug Delivery: A Review).
Matsuda teaches methods of suppressing myeloid-derived suppressor cells (MDSCs), reducing immune
suppression, reducing regulatory T-cell count and increasing CD4+ T-cell count in cancer patients using
ibudilast. See the abstract. Matsuda further teaches a method of reducing immune suppression in a
patient diagnosed with microorganism infection or suffering therefrom, the method comprising:
administering to the patient a therapeutically effective amount of ibudilast, or a pharmaceutical salt
thereof. See Para [0011]. The use of ibudilast for reduction or reversal of progressive
neurodegenerative diseases is taught in Para [0056]. The concentration of ibudilast is taught in Para
[0076] and [0090]. Matsuda teaches an ibudilast-based formulation of the present disclosure may be
administered for therapy by any suitable route, including without limitation, oral, rectal, nasal, topical
(including transdermal, aerosol, buccal and sublingual), vaginal, parenteral (including subcutaneous, intravenous, intramuscular, and intradermal), intrathecal, and pulmonary, in some embodiments, the
ibudilast-based formulation is administered orally. In some embodiments, the ibudilast-based
formulation is administered through an injection. The use of hydroxypropyl cyclodextrin as an excipient
is taught in Para [0082]. The use of Cremophor, which is polyoxyl castor oil is taught in Para [0082]. The
use of sodium phosphate monobasic, sodium phosphate dibasic, and combinations thereof is taught in
Para [0085]. The cancer of lung is taught in Para [0158].
Matsuda differs from the claimed invention in the use of propylene glycol and sulfobutylether
cyclodextrin.
Wang teaches a pharmaceutical composition comprising two or more compounds, wherein each
compound is independently a phosphodiesterase inhibitor, an adenosine receptor antagonist, a calcium
channel blocker, a histamine H1-receptor agonist, a histamine H2 -receptor agonist, a histamine H3-
receptor antagonist, or a ß2-adrenoreceptor agonist. see the abstract. The use of propylene glycol is
taught in Para [00272]. Wang teaches complexing agents include, but are not limited to, cyclodextrins,
including a-cyclodextrin, ß-cyclodextrin, hydroxypropyl-ß- cyclodextrin, sulfobutylether--cyclodextrin,
and sulfobutylether 7- -cyclodextrin. See Para [00287]. Wang makes clear that the claimed cyclodextrin
has been previously used in combination with a phosphodiesterase inhibitor. Ghate teaches SBE-B-CD
is a versatile derivative of the parent ß-CD. The ability to solubilize poorly soluble drugs is higher than
parent ß-CD due to the presence of hydrophobic butyl moiety. SBE-B-CD can be applied for use in
formulation of various drug delivery systems incorporating a variety of guest molecules ranging from
small molecules to large compounds, peptides and proteins. An optimized inclusion complex can be an
efficient strategy to increase the solubility of poorly soluble compounds and provide stability to a large
number of active pharmaceutical ingredients. Being able to be produced from extremely simple
processes, SBE-B-CD inclusion complexes can be a viable technique to reduce the dose of the drug
candidates.
It would have been obvious to a person skilled in the art to use sulfobutylether cyclodextrin in the
composition of Matsuda, motivated by the teachings of Wang, which teaches the use of the claimed
cyclodextrin in combination with phosphodiesterase inhibitors as old and well known. The use of
propylene glycol is also taught by Wang. Ghate teaches the advantages of the claimed cyclodextrin in
drug delivery. The determination of optimum proportions or amounts are considered to be within the
skill of artisan in the absence of evidence to the contrary. Applicant's attention is drawn to In re Aller,
220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), the court stated that "Generally, differences in
concentration or temperature will not support the patentability of subject matter encompassed by the
prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the
general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or
workable ranges by routine experimentation."
The use of ibudilast for the treatment of disorders of claims 18-20 is taught by Matsuda.
Applicant has presented no evidence to the unexpected or unobvious nature of the claimed invention,
and as such, claims 1-6 and 18-20 are properly rejected under 35 U.S.C. 103 (a).
Response to Arguments
Applicant’s arguments have been noted. Applicant in his remarks argues that “Wang is directed to pharmaceutical compositions comprising two or more compounds for
treating, preventing, or ameliorating a cardiovascular disease in a subject. Wang at Abstract.
Wang broadly discloses that its compositions may be administered orally, parenterally, or
topically, and may make use of modified release dosage forms, such as matrix-controlled release
devices, osmotic controlled release devices, or multiparticulate controlled release devices. Wang
also describes hundreds of excipients that may be used for such formulations. Id. at paragraphs
[00260]-[00331]. Wang's examples largely describe efforts to explore the administration of
two-, three-, or four-drug combinations to treat bradycardia, but Wang only explicitly teaches
one formulation in its examples: an oral capsule formulation of four drugs (theophylline,
nifedipine, betahistine dihydrochloride, and levalbuterol hydrochloride) with microcrystalline
cellulose, mannitol, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, and
citric acid. Id. at Example 4. Accordingly, Wang provides no specific guidance to one of ordinary skill in the art to particularly select sulfobutylether-ß-cyclodextrin (SBE-β-CD) as an excipient for an injectable pharmaceutical composition consisting of a buffered aqueous solution comprising ibudilast as described in the instant claims”. It is the examiner’s position that Matsuda teaches an ibudilast-based formulation of the present disclosure may be administered for therapy by any suitable route, including without limitation, oral, rectal, nasal, topical (including transdermal, aerosol, buccal and sublingual), vaginal, parenteral (including subcutaneous, intravenous, intramuscular, and intradermal), intrathecal, and pulmonary, in some embodiments, the ibudilast-based formulation is administered orally. In some embodiments, the ibudilast-based formulation is administered through an injection. The use of hydroxypropyl cyclodextrin as an excipient is taught in Para [0082]. The use of Cremophor, which is polyoxy castor oil is taught in Para [0082]. The use of sodium phosphate monobasic, sodium phosphate dibasic, and combinations thereof is taught in Para [0085]. The cancer of lung is taught in Para [0158]. The difference between Matsuda and the claimed invention is using sulfobutylether-B-cyclodextrin instead of hydroxypropyl cyclodextrin. Wang and Ghate provide ample motivation for a person skilled in the art to select sulfobutylether-B-cyclodextrin in place of hydroxypropyl cyclodextrin, considering that Wang teaches the use of sulfobutylether-B-cyclodextrin in combination with pharmaceutical formulation by injection as old and well known. Wang also teaches the use of phosphodiesterase inhibitors, which ibudilast is considered as one of them in combination with sulfobutylether-B-cyclodextrin. Ghate teaches the desirability of sulfobutylether-B-cyclodextrin over other types of cyclodextrin in pharmaceutical formulations. Applicant is reminded that the rejection is obviousness and not anticipation. Applicant in his remarks further argues that “Most of the solubilizers provided better ibudilast
solubility than HP-β-CD or SBE-ß-CD, but the resultant solutions suffered from poor shelf
stability, demonstrating flocculation or precipitation. Unexpectedly, a solution of SBE-β-CD
and a low concentration of ibudilast under buffered conditions exhibited excellent stability under
various conditions and time periods. Such results were not taught nor suggested by the cited
references”. It is the examiner’s position that there is no evidence to the superior stability of the claimed composition commensurate in scope with the claimed language over the prior art of record. Applicant is requested to provide such data.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZOHREH A FAY whose telephone number is (703)756-1800. The examiner can normally be reached Monday-Friday 9:30AM-6:00.
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/ZOHREH A FAY/Primary Examiner, Art Unit 1617