DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Preliminary Amendments and Remarks, filed 28 October 2025, in the matter of Application N° 18/408,664. 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 .
Claim 1 has been canceled. Claims 2-21 are newly added and supported by the originally-filed disclosure.
None of the newly added claims has been amended. No new matter has been added.
Thus, claims 2-21 now represent all claims currently under consideration.
Information Disclosure Statement
Three Information Disclosure Statements (IDS) filed 26 April 2024, 11 August 2025, and 7 April 2026 are acknowledged and have been considered.
Specification - Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
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 2-14, 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Qingpo et al. (CN 101322719A; IDS reference of record; machine translation cited).
The limitations of the claimed invention are directed to a solid pharmaceutical composition comprising: arsenic trioxide, a surfactant, a bulking agent, and a lubricant. The arsenic trioxide is recited as being present in an amount of from about 1 mg to about 20 mg.
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. Example 10, starting at ¶[1067], for instance, discloses a formulation comprising 10 mg of arsenic trioxide. The Example also discloses mannitol (bulking agent) and lecithin (surfactant). The amount of lecithin present in the formulation is 700 mg which is less than 50% of the overall formulation, thereby meeting claim 4.
Paragraphs [0049] and [0054] disclose that the practiced solid pharmaceutical compositions may further contain excipients such as talc and/or magnesium stearate.
The foregoing is thus considered to teach and suggest the limitations of instant claims 2-7.
Paragraphs [0049] and [0052] disclose that the excipient may also include a suspending agent such as polyvinylpyrrolidone (PVP), thereby teaching and suggesting the limitations recited by instant claim 8.
The foregoing is thus considered to additionally teach the limitations of claims 9, 11-13, 16, and 17.
Instant claim 10 recites that the surfactant is present in an amount ranging from about 1-10 mg. Instant claim 14 recites that the arsenic trioxide is present in an amount ranging from about 1-5 mg.
The reference more generically discloses that arsenic trioxide is present in a range from about 0.1-10% and the emulsifier (surfactant) is present in an amount ranging from about 0.2-10%. See ¶[0020]-¶[0023]. Such is considered to provide overlapping disclosure for the recited components of claims 10 and 11. This teaching is also considered to meet the limitations recited by claim 3, wherein the claim is also interpreted as reciting that the surfactant is present in an amount which does not exceed an amount of 50% of the arsenic trioxide present. That is, if the composition comprises 10 wt% arsenic trioxide, then the surfactant will not be more than 5 wt% of the composition. The Examiner submits that the limitations of instant claim 3, while not indefinite, are open to both interpretations with regard to the amount of surfactant.
Lastly, ¶[0004] is considered to teach and suggest the limitations recited by instant claims 18 and 19. Therein, the passage discloses that “[s]ince its experimental use in the 1970s to treat acute promyelocytic leukemia (APL), it has gradually been accepted and widely used in clinical practice.” Such is considered to teach, if not minimally suggest that that arsenic trioxide is well known and established in the art as being a treatment for APL.
Based on the combined teachings of the reference, 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.
Claims 2-21 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 Pre-Grant Publication Nº 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 claim 14 further limits the surfactant (e.g., sodium lauryl sulfate), while claim 20 recites a method of treating acute promyelocytic leukemia comprising the daily administration of the recited composition. Claim 21 recites that the method further comprises administering retinoic acid.
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 1-60 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 0.2-2 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], respectively.
Claim 3 additionally defines the homogenising agent as including polyvinyl pyrrolidone (PVP) which reads on the instantly recited binding agent. Claim 6 discloses that the homogenising agent may be hydroxypropyl methylcellulose.
Thus, the Examiner submits that the reference teaches and suggests the limitations of the instantly claimed compositions recited by claims 2-17.
Regarding the limitations recited by claim 4, the Examiner again submits, given the language used that the claim is not indefinite, but it can be read in two different manners. First, the claim states that the surfactant is present in an amount of not more than (NMT) about 50% based on the amount of arsenic trioxide. On one hand, this may be interpreted as being present in an amount such that the surfactant does not exceed 50% of the arsenic trioxide in the composition. However, alternatively, the Examiner submits that “does not exceed 50% based on the arsenic trioxide” is broadly stated in the sense that a fair interpretation of the claim is that it does not exceed 50% of the composition (by weight).
The Examiner submits that regardless of the interpretation, the claim is met by the foregoing disclosure since the practiced amounts of SLS and arsenic trioxide are considered to encompass the recited weight ranges. See MPEP §2144.05(I).
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 claim 21, whereby the method of treating APL further comprises 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.
Nonstatutory 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 2-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 19/349,368 (reference application).
Claim 2 of the instant application recites:
A solid, oral pharmaceutical composition, comprising:
arsenic trioxide in an amount of from about 1 mg to about 20 mg;
a surfactant;
a bulking agent; and
a lubricant.
Reference claim 1 more generically recites:
A solid, oral pharmaceutical composition, comprising:
arsenic trioxide in an amount of from about 1 mg to about 20 mg;
a surfactant; and
one or more pharmaceutically acceptable excipients.
The limitations of reference claim 2 read directly on instant claim 3.
The limitations of reference claims 3, 4, 7, 8, 11, 12, 23, and 24 read on instant claims 5-9.
The limitations of reference claim 22 read on instant claims 2, 4, and 14.
The limitations of reference claims 5, 9, and 22 read on instant claims 2, 10, and 14.
The limitations of reference claims 6 and 10 read on instant claim 3 and 10.
The method limitations of reference claims 13-21 and 25-30 read on each of the groupings of instant claims 18-20.
Thus, were the ‘368 reference application available as prior art, the Examiner advances that it would render the instantly claimed inventions prima facie obvious where it did not anticipate it.
This is a provisional nonstatutory double patenting rejection.
Claims 2-7 and 11-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 15-18 of Vaddi et al. (USPN 12,364,664 B2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations of claim 1 of the ‘664 patent disclose:
A solid, oral pharmaceutical composition comprising:
a bulking agent;
a lubricant; and
a lyophilized composition comprising arsenic (LCCA) made by a method comprising
combining arsenic trioxide powder, water, and an alkalizing agent to obtain a pH of at least 12, followed by adding an acid to adjust the pH to about 7 to about 8, thereby generating a solution comprising arsenious acid;
adding surfactant to the solution comprising arsenious acid; and
lyophilizing the solution comprising arsenious acid and the surfactant to obtain the LCCA.
The limitations of claims 2 and 3 disclose that the LCCA and the composition comprise about 24-29% of the LCCA and about 69-74% of the bulking agent in the composition.
Claims 15 and 16 disclose that the resulting formulation is a capsule or tablet.
Claim 17 discloses that the capsule will contain between 0.25-50 mg of the LCCA.
Given that the disclosed LCCA ultimately represents 24-29% of the composition, at most, the practiced capsules will contain 12-14.5 mg of LCCA which is composed of arsenic trioxide and surfactant.
Claim 7 of the ‘664 patent discloses further that the amount of the surfactant by weight does not exceed 50% the amount of the arsenic trioxide by weight.
Thus, in considering the composition of the LCCA and the portions assigned to its constituents, the ordinarily skilled artisan will understand that the LCCA will, at most contain 6-7.25 mg of arsenic trioxide and surfactant each. Such is considered to teach the limitations of both arsenic trioxide and surfactant (e.g., SLS) as instantly recited.
Claims 5 and 6 disclose sodium lauryl sulfate (SLS) as a surfactant.
Claim 4 discloses mannitol as a bulking agent and talc and/or magnesium stearate as the lubricant.
The Examiner thus submits that a person of ordinary skill in the art in possession of the ‘664 patent would have had a reasonable expectation of successfully producing the instantly claimed composition. Were the ‘664 patent available as prior art, the Examiner advances that it would have rendered the instantly claimed composition prima facie obvious for the reasons discussed above.
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
Prosecution Insights