DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Amendments and Remarks, filed 2 June 2026, in the matter of Application N° 19/349,368. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
No claims have been added or canceled.
Claims 1, 4, 8, 12, 13, 16, 19, 23-25, and 28 have been amended. Claim 1 has been amended to further limit the surfactant to an amount that is about 10% to about 50% of the amount of arsenic trioxide. Support is provided for the amendment. The remaining claims are editorially amended (i.e., adding a missing word) and do not change the scope of the subject matter at issue.
No new matter has been added.
Thus, claims 1-30 continue to represent all claims currently under consideration.
Information Disclosure Statement
One new Information Disclosure Statements (IDS) filed 2 June 2026 is acknowledged and has been considered.
Withdrawn Rejections
Rejection under 35 USC 102
Applicants’ amendment to claim 1 alters the interpretation of the invention at issue and thus overcomes the previously raised rejection over Qingpo. The current form of the rejection is withdrawn and a new rejection over the reference appears herein below.
Rejections under Nonstatutory Double Patenting
Applicants’ submission of an electronic Terminal Disclaimer (“eTD”) is acknowledged in response to the rejections previously raised over copending application 18/408,664 and granted patent USPN 12,364,664 B2. The eTD was approved upon submission and the rejections are overcome and thus withdrawn.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 2 March 2026 since the art that was previously cited continues to read on the amended and previously recited limitations.
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. Applicants are 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 1-30 are rejected under 35 U.S.C. 103 as being unpatentable over Nguyen (US Pre-Grant Publication Nº 2012/0245156 A1; IDS reference of record), in view of Kwong (US 2008/0089951 A1), and further in view of Zhou et al. (PloS Med; 2005).
The limitations of the claimed composition are discussed above. The limitations of the remaining dependent claims further limit the surfactant (e.g., sodium lauryl sulfate), the excipients (i.e.; mannitol, talc, etc.). Claims 13, 16, 19, 25, and 28 recite a method of treating acute promyelocytic leukemia comprising the daily administration of the recited composition.
Nguyen discloses preparing solid dosage forms comprising at least one active pharmaceutical ingredient (API), at least one homogenising agent, one binding agent and/or one filler (see e.g., Abstract; claims; ¶[0048]).
The homogenising agent is further defined in the claims as representing various ranges of the total dry component of the oral dry composition: about 0.001% to about 10%, about 0.1% to about 5%, and from about 0.1% to about 1% (see e.g., claims 10-12). The homogenising agent is additionally defined as being selected from sodium lauryl sulfate (see e.g., claim 9; ¶[0096]).
The API is taught as being able to be selected as arsenic trioxide (see e.g., claim 16; ¶[0101]). The amount of API used within the solid tablets is disclosed as being as broad as from about 0.001% to about 80% by weight of the total dry weight of the tablet and as narrow as about 0.5% to about 30% by weight of the tablet.
Table 5 provides exemplary batch productions for 200 mg tablets, thus providing the skilled artisan with a target tablet weight off of which to base the amounts of ingredients.
Thus, it would be well within the purview of the ordinarily skilled artisan to calculate the weight of API and homogenising agent within the manufactured oral tablet. Regarding instantly claimed composition, the reference most preferably discloses that the API is present 0.5-30% of the dosage form, which based on a 200-mg tablet, recalculates to a mass ranging most preferably from 1-30 mg of API (i.e., arsenic trioxide). Similarly, the homogenising agent being present in an amount ranging most preferably from 0.1% to about 1%, in a 200-mg tablet, would then possess between about 0.1-1 mg of homogenising agent (e.g., SLS).
Magnesium stearate is disclosed as another species of surfactant that may be used. Mannitol is disclosed as a preferred filler component for the tablets. See e.g., ¶[0096] and ¶[0121].
Thus, the Examiner submits that the reference teaches and suggests the limitations of the instantly claimed compositions recited by claims 1-12 and 22-24.
The reference is acknowledged as possessing two key deficiencies. First, the Examiner submits that arsenic trioxide as the API is one that may be selected from a larger list of APIs, but is nevertheless, taught and suggested. Secondly, the reference does not expressly teach or suggest treating acute promyelocytic leukemia with a composition comprising arsenic trioxide, a surfactant, and at least one excipient.
Kwong is considered to remedy both of these deficiencies disclosing the preparation and administration of oral dosage forms such as tablets and capsules comprising arsenic trioxide as the active ingredient (see e.g., Abstract; claims 1, 10-12), with claim 11 disclosing preferred dose amounts ranging from 5-10 mg. Paragraph [0037] discloses that surfactants such as SLS, Spans, and Tweens are included with the dosage form.
The reference additionally discloses that arsenic trioxide is highly efficacious in the treatment of acute promyelocytic leukemia (APL), and that it is the standard treatment for APL. See ¶[0007], ¶[0024], and ¶[0026].
Wherein Nguyen and Kwong are deficient is with respect to the limitations recited by claims 15, 18, 21, 27, and 30, whereby the respective methods of treating APL further comprising administering retinoic acid.
Zhou is considered to bridge this gap in its disclosure of testing the efficacy of all-trans retinoic acid (ATRA), arsenic trioxide, of a combination of the two, for their respective groups’ ability to degrade the promyelocytic leukemia retinoic acid receptor α (PML-RARα) oncoprotein. Each group was tested, and while all groups demonstrated complete remission (CR) of greater than 90%, the combination of ATRA and arsenic trioxide took the least amount of time to achieve CR (see e.g., pg. 0035, last column).
Thus, while the Examiner acknowledges that Zhou does not disclose administering the instantly claimed composition, it does provide very clear motivation to the skilled artisan to modify the teachings of Nguyen to select arsenic trioxide for the practiced dosage. It further motivates said artisan to treat a patient suffering from APL with a dosage form containing both arsenic trioxide and ATRA.
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited method of treatment. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Response to Arguments
Applicants’ arguments with regard to the rejection of claims 1-30 under 35 USC 103(a) as being unpatentable over the combined teachings of Nguyen et al., Kwong, and Zhou et al. have been fully considered but they are not persuasive.
Applicants traverse the rejection on the grounds that the amended limitations of claim 1 are neither taught nor suggested by the combined teachings of the references.
The Examiner disagrees.
At the outset, the Examiner notes that Applicants’ remarks address only the teachings of Nguyen and only with respect to instant claim 1. Applicants’ mention of the secondary references Kwong and Zhou is noted.
Applicants’ position asserting non-obviousness focuses on the teachings from a physiochemical property noting that “[c]onventional arsenic trioxide has a low water-solubility” and cites ¶[0019] of the published application. The Examiner notes this corresponds to ¶[0019] of the originally-filed specification, in addition to there being no actual solubility value discussed; only that it is ‘sparingly and extremely slowly soluble in cold water; even in boiling water it is only soluble in a 1:15 ratio’, according to the 1989 Merck Index.
PubChem (CID 14888) discloses that arsenic trioxide has a solubility in water at 20ºC ranging from 1.2-3.7 g/100mL or 12-37 mg/mL.
PubChem (CID 3339) linking to the Human Metabolome Database (www.hmdb.ca/metabolites/HMDB0015173) discloses that fenofibrate is practically insoluble in water with a value of 0.00071 g/L (or mg/mL).
PubChem (CID 3957) linking to the Chemical Book (www.chemicalbook.com/ChemicalProductProperty_US_CB5283770.aspx) discloses that loratadine has a solubility in water at 25ºC of less than 1 mg/mL. Additional state-of-the-art teachings such as Bandari et al. (J. Pharm. Innov.; 2014), more specifically disclose the solubility of loratadine in water as being 3.27 µg/mL (or 0.00327 mg/mL) (see pg. 143; Results and Discussion).
Lastly, PubChem (CID 54676228) linking to the Human Metabolome Database (www.hmdb.ca/metabolites/HMDB0014694) discloses that piroxicam has a solubility in water of about 0.14 g/L (or about 0.14 mg/mL).
What the state-of-the-art thus demonstrates is that while each of the aforementioned APIs is deemed “sparingly water-soluble”, that definition is orders of magnitude in scope. Arsenic trioxide is the most soluble of the four mentioned and relied upon in support of Applicants’ position.
The Examiner respectfully submits that Applicants’ assertion that one would not arrive at the amended invention based on the teachings of Nguyen, based on the exemplified formulations in Examples 4-6 (Example 3 contains no surfactant), is not persuasive. Of the four APIs mentioned, piroxicam is the next API that is less soluble than arsenic trioxide; arsenic trioxide is about 85 times more soluble than piroxicam ([12 mg/mL][0.14 mg/mL]).
In reconsidering the teachings of Nguyen in view of the filed amendment, the Examiner submits that the homogenising agent is taught as being present in the composition in an amount ranging from about 0.001% to about 10% by weight of the total dry weight of the composition (see e.g., claim 10), from about 0.1 to about 5% by weight of the total dry weight of the composition (see e.g., claim 11), and from about 0.1 to about 1% by weight of the total dry weight of the composition (see e.g., claim 12). See also ¶[0098]. Paragraph [0102] discloses the API will be present in amounts ranging as broad as about 0.001% to about 80% by weight of the total dry weight of the composition and most preferably, from about 0.5% to about 30% by weight of the total dry weight of the composition.
The foregoing teachings provide the ordinarily skilled artisan the guidance to arrive at the claimed combination of amounts of surfactant and API. The teachings of Kwong provide further motivation to select arsenic trioxide from the broader teachings of Nguyen to produce the claimed formulation.
No evidence of criticality has been provided by Applicants in support of a showing of non-obviousness.
Applicants’ arguments, for the above reasons, are found unpersuasive. Said rejection is therefore maintained.
New Rejections
Applicants’ amendments have necessitated the following ground of rejection:
Claim Rejections - 35 USC §102/§103
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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. Applicants are 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 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Qingpo et al. (CN 101322719A; IDS reference of record; machine translation cited).
As amended, the limitations of the claimed composition recite a solid, oral dosage form comprising about 1-20 mg of arsenic trioxide, a surfactant (emulsifier) in an amount of from about 10% to about 50% of the arsenic trioxide, and one or more pharmaceutically acceptable excipients.
Qingpo discloses a solid pharmaceutical composition comprising arsenic trioxide, an emulsifying agent, an optional co-emulsifying agent, and one or more excipients (see e.g., Abstract; claim 1). Paragraph [0049] defines the solid preparations as being a capsule or tablet. Embodiment 1, for instance, discloses a formulation comprising 10 mg of arsenic trioxide.
Claims 1 and 2 more generically discloses that the nanogranules, ultimately used to prepare tablets, consist of up to about 10% w/v of arsenic trioxide in a formulation that has a final volume of 100 mL (i.e., about 10 mg). The emulsifying agent in claim 1 is disclosed as ranging from about 1-20 wt% and in claim 2 as ranging from about 2-10 wt%, thereby encompassing the amended limitation of the surfactant being present in an amount ranging from about 10-50 wt% with respect to the amount of arsenic trioxide present in the formulation. The secondary emulsifying agent (co-emulsifier) is taught as being optional (i.e., 0 wt%) in both claims.
The reference is thus considered as teaching each of the instantly claimed limitations. To the extent that the instantly claimed subject matter is not anticipated by the descriptive matter of the reference, it would be so recognized by persons of ordinary skill in the pharmaceutical arts. Of particular note, the amount of emulsifying agent disclosed by the reference is presented in an amount that overlaps with the instantly claimed weight range. MPEP §2144.05(I) states that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”
Thus, one would have more than a reasonable expectation of successfully creating the instantly claimed composition, particularly since the compositions taught in the reference, at the very least, represent obvious variations which very closely read on those compositions which are instantly claimed. Therefore, the invention as a whole would also have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, absent a clear showing of evidence to the contrary.
All claims have been rejected; no claims are allowed.
Conclusion
Applicants’ amendments necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP §706.07(a). 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 extension fee 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
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