DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Request for Continued Examination (RCE), Amendments and Remarks, filed 7 October 2026, in the matter of Application N° 19/349,368. Said documents have been entered on the record. The Examiner further acknowledges the following:
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 7 October 2026 has been entered.
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, 15, 18, 21, 27, and 30 have been amended. Claims 15, 18, 21, 27, and 30 have been editorially amended and add no subject matter. Claim 1 has been amended as discussed below. Of particular note is the addition of a comparative dissolution property to the previously recited composition. No additional compositional or structural limitations have been added to the claims.
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 Statement (IDS) filed 7 October 2026 is acknowledged and has been considered.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 10 June 2026 since the art that was previously cited continues to read on the amended and previously recited limitations.
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.
Response to Arguments
Applicants’ arguments with regard to the rejection of claims 1 and 5 under 35 USC 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Qingpo et al., have been fully considered, but are not persuasive.
Applicants initially traverse the rejection on the ground that the reference does not teach the amended property of the composition. Therein, as amended, claim 1 now recites a solid oral pharmaceutical composition comprising arsenic trioxide in an amount ranging from about 1-20 mg; a surfactant present in an amount ranging from about 10-50% of the amount of arsenic trioxide (i.e., from about 0.1-10 mg), and one or more pharmaceutically acceptable excipients.
As amended, the composition comprising arsenic trioxide and surfactant exhibits a dissolution property wherein the arsenic trioxide dissolves 8.6 times more than the unformulated arsenic trioxide when each is tested in 900 mL 0.1N HCl using a paddle apparatus at 100 rpm at 30 minutes.
The Examiner acknowledges that the specific property amended into claim 1 is not disclosed by the reference.
Applicants’ remarks additionally take issue with the Examiner’s assessment of the composition pointing out that Qingpo’s solid lipid nanoparticle formulation comprises in addition to arsenic trioxide and an emulsifier, other compounding agents, collectively referred to by Applicants as solid lipid formulation ingredients (or SLFIs) with no indication that they may be optional or irrelevant (i.e., they are required ingredients).
Applicants argue that “[t]he Office’s analysis effectively extracts two components (ATO and emulsifier) from Qingpo’s multi-component solid lipid nanoparticle formulation, and treats those components as though Qingpo disclosed them independently or the remainder of the nanoparticle system” and that “Qingpo does not disclose or suggest its emulsifier in isolation”. It is lastly argued that “[t]he Office has not identified a suggestion or disclosure in Qingpo that one should omit the phospholipid and solid lipid material while retaining the selected ATO and emulsifier amounts.”
The Examiner, in response, respectfully submits that the scope of the claimed composition does not require addressing of the remaining ingredients of the compositions practiced by Qingpo beyond acknowledging them as meeting the final compositional requirement of the claim. Applicants are directed to MPEP §2111.03(I) regarding the scope of the transitional phrase “comprising”.
As acknowledged by Applicants in their filed response, Qingpo does in fact meet the compositional limitations for arsenic trioxide (e.g., 10 mg) as well as disclosing an emulsifying ingredient (aka surfactant) which minimally teaches and suggests the fractional weight percentage with respect to the amount ATO present (see e.g., claim 2).
The remaining elements of the practiced composition are not excluded by the scope of the claimed composition and no additional structural limitations or relationships are set forth in the rejected claims.
Regarding the addition of the dissolution property to the claimed composition, MPEP §2112.01(I) states that “[w]here the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established.”
Further, MPEP §2112(I) states that “the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.”
As discussed above, the Examiner has provided Applicants with such a showing in the teachings of Qingpo. Applicants’ response has provided no evidence distinguishing the claimed composition from this disclosure.
For these reasons, Applicants’ arguments are found unpersuasive. Said rejection is therefore maintained.
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’ initial remarks traversing the rejection state that “[t]he presently claimed limitation does not define the surfactant as a percentage of a total dosage form. Rather, amended claim 1 requires the surfactant to be present ‘in an amount of from about 10% to about 50% of the amount of arsenic trioxide.’ Thus, the amount of ATO, not the total weight of a tablet, is the reference quantity against which the surfactant amount is determined.”
The Examiner agrees with this, in part. However, overall, the scope of the claimed composition conflicts with Applicants’ argument. The amended claim recites a solid, oral pharmaceutical composition comprising a composition comprising arsenic trioxide, a surfactant, and one or more pharmaceutically acceptable excipients.
The Examiner acknowledges the ranges of amounts for ATO and the surfactant and that the latter range depends on the former. However, there is no reference amount for the “sub-composition” (i.e., ATO, surfactant and excipient(s)) within the overall oral solid dosage form. As such, the broadest reasonable interpretation of the amended composition is that the composition comprises from about 1-10 mg of ATO and so on.
Based on the foregoing assumption, Applicants assert further that Nguyen independently expresses the API and homogenizing agent amounts relative to the total dry weight of the composition or an example tablet.” It is also alleged that “Nguyen does not disclose or suggest the claimed surfactant-to-ATO relationship” and that the reference does not disclose that “the amount of homogenizing agent should be selected based upon, or as a percentage of, the amount of API.”
The Examiner respectfully submits that, as discussed above, the interpretation of claim 1 as amended, does not require this. Yes, the claim recites an amount of surfactant be present with respect to the mass of ATO, however, there is no limit on what percentage of the total dosage form is given to the “sub-composition” of the claim.
Further, in response to Applicants’ perceived conditions that must occur for the skilled artisan to arrive at the claimed invention, the Examiner submits that Nguyen provides the requisite guidance.
The skilled artisan must select a particular ATO concentration from the reference’s disclosed API range. Therein, ¶[0102] discloses that the API is most preferably present in the tablet in an amount ranging from 0.5% to about 30% by weight (e.g., 0.5-30 mg of a 100-mg tablet).
Next the homogenizing agent amount must be independently selected from a separately disclosed range. Therein, the reference discloses that the homogenizing agent will most preferably range from 0.1% to about 1% of the dosage form and at most 10% by weight (see e.g., claims 10-12; and ¶[0098]).
Lastly, the mathematical calculation to determine an amount of surfactant that meets the amount of ATO is well within the purview of the ordinarily skilled artisan.
It is further asserted that, in response to the Office’s argument of Applicants’ failure to provide a showing of criticality for the recited amounts, that the present traversal does not depend upon the establishing of criticality of the previously claimed numerical endpoint, and that claim 1, as amended, requires a composition comprising ATO and a surfactant exhibiting the 8.6x dissolution limitation.
The Examiner, in response, submits that Nguyen teaches and suggests the claimed composition and again refers Applicants to MPEP §2112.01(I).
Further, Applicants’ remarks directed to the method by which Nguyen’s product is manufactured are acknowledged, but are not persuasive simply because there is no method of manufacture at issue in the rejected claims.
Applicants state that Nguyen does not report on the dissolution of any composition comprising ATO and a homogenizing agent, because Nguyen does not exemplify ATO at all.
MPEP §2123(I) and (II) respectively state that “[a] reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” and “[d]isclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments.”
Applicants’ remarks to the Examiner’s reliance upon the PubChem entries is acknowledged. Contrary to the assertion, the weblinks to the relevant entries were provided in the previously presented correspondences as references to the state-of-the-art pertaining to defining properties of compounds that are well-entrenched within the prior art. The Examiner is relying upon these showings to define compounds that are available well ahead of the effective filing date of the instant application. Applicants are directed to MPEP §2112.01(II) which states that “[p]roducts of identical chemical composition cannot have mutually exclusive properties.”
Regarding the newly recited property amended into claim 1, the Examiner maintains, as in the preceding rejection, that the composition at issue, remains taught and suggested by the reference(s) of record. The recited composition contains no structural or compositional distinctions from the cited art.
Applicants remarks directed to the comparison of “unformulated ATO” to “formulated ATO” are acknowledged as are the continued references to Experiment No. L040/1/001B. However, the cited example and the arguments over the alleged distinction in properties are not commensurate in scope with the breadth of the claimed composition. Thus, whether the Examiner acknowledges that the unformulated ATO material is materially different from the exemplified composition comprising ATO and a surfactant is immaterial simply because it is not at issue.
What is instead at issue is the fact that Nguyen teaches and suggests the claimed composition, which is a solid, oral dosage form comprising ATO, a surfactant (i.e., SLS), and one or more excipients. The cited L040 experiment series summarized in the remarks and in the instant disclosure are not consistent with the composition as instantly claimed. The cited experiments each evaluate the ability of arsenic trioxide to dissolve into solution using a different pairing of solvent and solubility enhancer. L0040/1/001B, is noted as using sodium lauryl sulfate and purified water. On its face, with respect to the scope of amended claim 1, this presents as conflicting evidence which would convey to the skilled artisan that the instantly amended composition lacks enablement. That is, the claimed composition is recited as a composition of ATO and a surfactant (e.g., SLS) having improved solubility, while the instant specification (e.g., ¶[0222]) describes such a formulation as not being dissolvable.
Applicants’ arguments, for the above reasons, are found unpersuasive. Said rejection is therefore maintained.
All claims have been rejected; no claims are allowed.
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
