DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Status of Claims
The amendment, filed on 10 February 2026, is acknowledged.
Claims 1 and 16 have been amended.
Claims 1-3, 5, 7-12, 14, and 16-20 are pending and under consideration in the instant Office Action.
Objections Withdrawn
Objections to Claims
Applicant’s amendment to claims 1 and 16, submitted on 10 February 2026, has overcome the objection to the claims set forth in the Office Action mailed on 23 October 2025. Accordingly, the relevant objections are withdrawn.
Maintained Objections
Claims
Claim 5 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Appropriate correction is required.
Response to Remarks
The Applicant’s remarks, filed on 10 February 2026, regarding the difference between a pharmaceutical composition and oral solid tablet are acknowledged, particularly relevant to this response the statement that “a pharmaceutical composition is broader in scope than a solid tablet” (pg. 6, Claim Objections, para. 2). However, no limitations are present in claim 1 to distinguish the claim from claim 5. Replacing the words “pharmaceutical composition” with “nitroxoline oral solid tablet” in lines 1, 5, 8, 11-12, 15, 16, and 17 of claim 1, and adding “as an active ingredient” produces the identical claim recited in claim 5. For these reasons, the objection is maintained.
Maintained Rejections
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.
Claims 1-2, 5, 7, 9-10, 12, 16, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Bykov et al. (Russia Patent No. RU 2149632 C1, published on 27 May 2000, hereafter referred to as Bykov) in view of Li et al. (Lubricants 2014, 2 (1), 21., hereafter referred to as Li).
Bykov teaches a pharmaceutical composition in the form of a coated tablet containing the active pharmaceutical ingredient nitroxoline (Abstract). The core of said tablet is taught to contain nitroxoline at 38-62% of the total composition weight, starch at 12-30% by weight, and slipping substances, which are interpreted as being equivalent to lubricants, at 1-4% by weight (Abstract, claim 1, example 1). The starch is taught to act as a filler accounts for 12-30% by weight of the composition, and is additionally taught to act as a binder during composition mixing (pg. 2, antepenultimate para.). The quantity of starch used as a binder is 5-10% by weight of the total mass of starch, resulting in 0.6-3.0% by weight of starch as a binder (pg. 2, antepenultimate para.). Milk sugar, which is interpreted to be equivalent to lactose, is also taught to be a filler and is present in an amount of 12-30% w/w (claim 1, Example 1).
Bykov also teaches that the disintegrating agent polyvinylpyrrolidone may be used at 0.5-2.6% by weight in the composition, but on the exterior of the tablet rather than in the core (claim 2). Aerosil® is included in the core of the composition at 1-10% by weight and, in light of the disclosure from Evonik Industries (included in office action as Evonik Industries Aerosil Pamphlet, published July 2015, accessed January 31, 2025), is interpreted to be equivalent to the core comprising a disintegrating agent as recited by the instant invention. The inclusion of Aerosil®, along with other excipients, is taught to modify the rate of API release following administration (pg. 2, para. 6 and 10).
Bykov further teaches coating the nitroxoline tablet with “sugar, basic magnesium carbonate, Aerosil®, talc, titanium dioxide, polyvinylpyrrolidone, dye and glossy substances” (claim 1). The coating taught by Bykov improves the taste of the composition while maintaining a strong, protective shell (pg. 2, antepenultimate para.) and maintains shelf stability for “more than 4 years” (pg. 2, penultimate para.). Following dissolution of the coating, Bykov teaches that the active substance is rapidly absorbed in the gastrointestinal tract, and the coating is therefore interpreted to be gastric-soluble (pg. 2, para. 12). The tablets in Example 1 gain 0.013 g following coating, increasing from an average mass of 0.187 g to 0.2 g, for a ~7% weight gain.
Guidelines on the obviousness of similar and overlapping ranges, amounts, and
proportions are provided in MPEP § 2144.05. With respect to claimed ranges which
“overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). These guidelines apply to the amounts of nitroxoline, filler, disintegrating agent, binder, and lubricant in the instant application. In each instance, the recited ranges either significantly overlap with or fall within the ranges taught by Bykov.
Bykov does not teach sodium dodecyl sulfate or sodium stearyl fumarate as a lubricant. This deficiency is offset by the teachings of Li.
Li teaches the utility of lubricants in pharmaceutical solid dosage forms, such as tablets, drawbacks associated with magnesium stearate and potential alternative lubricants (Abstract). Lubricants are taught to be essential components of drug formulations, reducing friction during manufacturing and enabling better component mixing (pg. 22, para. 1-2). Magnesium stearate and stearic acid are taught to be two of the most frequently used lubricants in pharmaceutical manufacturing, but alternatives are taught to exist and are discussed in the review to overcome drawbacks associated with magnesium stearate (pg. 22, para. 2 - pg. 23, para. 1).
Several factors are taught to be important to consider when selecting a lubricant, including shear strength, durability, toxicity, consistency between batches, and chemical compatibility with APIs (pg. 39, para. 1). Magnesium stearate is taught to form a variety of hydrates upon exposure to humidity, leading to commercial supplies frequently containing unknown mixtures of hydration states and inconsistency in the lubricity and shear strength of the chemical (pg. 29, para. 1 - pg. 30, para 1). In addition, magnesium stearate is taught to contain various impurities due to processes used in its manufacture, and these impurities can cause incompatibilities with some APIs (pg. 29, para. 2). For example, MgO impurities are taught to cause ibuprofen degradation in solid state commercial pharmaceutical products (pg. 35, para. 3). Further, magnesium stearate itself is taught to basify the pH conditions of its micro-environment, which can also cause degradation of APIs including acetylsalicylic acid (aspirin) (pg. 35, final para.). Finally, magnesium stearate is taught to be capable of slowing the dissolution of solid pharmaceutical compositions due to “excessive coating of granules by magnesium stearate” (pg. 37, final para.).
One alternative to magnesium stearate is taught to be sodium stearyl fumarate (pg. 37, final para. and pg. 38, final para.). “[W]hen replacing magnesium stearate with hydrophilic lubricants such as Stear-O-Wet® or sodium stearyl fumarate, the dissolution slow-down was not observed” (pg. 37, final para.). Sodium stearyl fumarate is taught to be a common alternative lubricant used in pharmaceutical formulations, in part due to its ability to be “supplied in a purer form” which leads to fewer incompatibility issues with APIs (pg. 37, final para. and pg. 38, final para.). The compound is further taught to be “less hydrophobic and has a less retardant effect on tablet dissolution than magnesium stearate”, making it appropriate as an alternative (pg. 38, final para.). Li concludes that “sodium stearyl fumarate appears to be a good alternative to magnesium stearate in certain solid dosage formulations” (pg. 38, final para.).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, in view of the teachings of Li to use sodium stearyl fumarate as a lubricant in the invention of Bykov because combination of components known in the prior art in similar inventions to impart a known benefit yields predictable results. Bykov teaches a pharmaceutical composition in the form of a solid tablet comprising nitroxoline as an API, starch as a filler and binder, polyvinylpyrrolidone as a disintegrating agent, and lactose as a filler, in quantities that either encompass or overlap with the ranges recited in the instant application. Additionally, Bykov teaches coating the solid pharmaceutical tablet in a gastric-soluble premix that results in a ~7% weight gain and the inclusion of lubricants, but does not teach specific lubricants. In view of the teachings of Li, an ordinary artisan would be motivated to try using sodium stearyl fumarate as a lubricant because Li teaches it to have fewer drawbacks than the more common lubricant magnesium stearate, appropriate to use as a lubricant in solid pharmaceutical compositions, and a suitable replacement for magnesium stearate. Further, because Bykov teaches that a lubricant should be used but does not teach a specific species, the teachings of Li regarding the inclusion of sodium stearyl fumarate would provide missing information required to enable the invention.
Claims 16 and 20 are interpreted as product-by-process claims. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). See MPEP § 2113. The patentability of instant claims 16 and 20 is determined by the product recited in claim 1, which was rendered obvious by the teachings of Bykov and Li, therefore claims 16 and 20 are also prima facie obvious. As a result, there is a reasonable expectation of success in arriving at the invention of instant claims 1-2, 5, 7, 9-10, 12, 16, and 20 in view of the teachings of Bykov and Li.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Bykov (Russia Patent No. RU 2149632 C1, published on 27 May 2000) in view of Li (Lubricants 2014, 2 (1), 21.), as applied to claims 1-2, 5, 7, 9-10, 12, 16, and 20 above, and further in view of Jordan (U.S. Patent No. 5,885,617 A, priority to 6 June 1995).
Bykov and Li teach the above.
Bykov and Li do not teach the coating to comprise polyvinyl alcohol (PVA). This deficiency is offset by the teachings of Jordan.
Jordan teaches a moisture barrier film composition that can be used to coat pharmaceutical tablets (Abstract). During storage, Jordan teaches that solid pharmaceutical compositions may undergo degradation due to atmospheric moisture and that special packaging is sometimes required to mitigate the moisture (column 1, lines 13-19). However, specialized packaging can be ineffective in humid climates, and Jordan teaches that similar protection may be achieved by “coating with materials which reduce the rate at which the dosage form absorbs atmospheric moisture” (column 1, lines 23-28).
To achieve the goals above, Jordan teaches a coating composition comprising polyvinyl alcohol (PVA), soya lecithin, and optionally a flow aid, colorant, and suspending agent, which can be dispersed in water and subsequently be applied to solid pharmaceutical tablets (column 1, lines 53 - column 2, line 7 and claims 1 and 18). PVA is taught to impart excellent moisture barrier properties without requiring heating of the coating composition (column 2, lines 38-45). The flow aid is taught to be talc, fumed silica, lactose, or starch (column 2, line 46). In some embodiments, the suspending agent may be hydroxypropyl methylcellulose or hydroxypropyl cellulose, and acts as a viscosity modifier that stabilizes the composition (column 2, lines 59-65 and claims 1 and 16-17). Finally, the colorant is taught to be food approved colors or dyes such as aluminum lakes, iron oxides, or TiO2, and in one embodiment is tartrazine aluminum lake (column 2, lines 47-50, Example 10, and claims 12, 17, and 29-31).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to use the moisture barrier coating taught by Jordan in the invention rendered obvious by the teachings of Bykov and Li because the use of a known technique to improve a known product for which the technique was designed produces predictable results. The teachings of Bykov and Li rendered obvious a solid pharmaceutical composition comprising nitroxoline as an API, starch as a filler and binder, polyvinylpyrrolidone as a disintegrating agent, and lactose as a filler, in quantities that either encompass or overlap with the ranges recited in the instant application, which is coated in a gastric-soluble coating premix. In view of the teachings of Jordan, an ordinary artisan would be motivated to use the moisture barrier film composition on the solid pharmaceutical tablet rendered obvious by Bykov and LI because Jordan teaches their PVA-containing composition to protect pharmaceutical tablets from degradation via atmospheric moisture. One of ordinary skill would find it desirable to protect their invention from degrading prior to reaching the consumer and to extend its shelf-life via increased protection. As a result, there is a reasonable expectation of success in arriving at the invention of claim 3 in view of the teachings of Bykov and Li and further in view of the teachings of Jordan.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Bykov (Russia Patent No. RU 2149632 C1, published on 27 May 2000) in view of Li (Lubricants 2014, 2 (1), 21.), as applied to claims 1-2, 5, 7, 9-10, 12, 16, and 20 above, and further in view of Cheng (U.S. Patent Application Publication No. US 2017/0065528 A1, published on 9 March 2017).
Bykov and Li teach the above.
Bykov and Li do not teach the weight gain of the coating to be 9-12% w/w. This deficiency is offset by the teachings of Cheng.
Cheng teaches an enteric film coating for drugs that imparts alcohol resistance and inhibits dose “dumping” (Abstract and para. [0001]). Drug “dumping” is taught to be a premature or exaggerate release of a drug from a pharmaceutical composition in a confined area that can result in “adverse physiological effects and, in extreme cases, drug-induced toxicity” (para. [0002]). This phenomenon is typically seen with drugs taken orally when in the gastrointestinal tract alongside alcohol (para. [0003-0004]). The goal of the invention of Cheng is to provide an alcohol resistant enteric drug coating “to ensure there is no change in the bioavailability of an API in the presence of alcohol in the GI tract” (para. [0009]).
To achieve this goal, Cheng teaches the use of a coating comprising an aqueous solution of a salt of alginic acid, a shellac, and an additive that may be a detackifier, slip aid, surfactant, plasticizer, preservative, opacifier, colorant, and combinations thereof (para. [0012] and [0036] and claims 1 and 8). The combination of alginate salt, shellac, and additive(s) produces a coating that does not rupture or disintegrate in the stomach (pH of ≤1.2), has limited API release over 2 hours in the stomach, has resistance to alcohol at low pH, and does release API at pH >4.5, the pH of the small intestine (para. [0062]). To achieve this result, Cheng teaches that the coating weight gain on a solid pharmaceutical tablet should be ≤15% w/w, or preferably between 1-10% w/w (para. [0078] and claim 17). This goal is validated in Example 5 and the bio-simulation tests presented in Tables 8-9.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the filing of the instant application, to combine the coating taught by Cheng with the solid pharmaceutical tablets rendered obvious by the teachings of Bykov and Li to arrive at the invention of claim 8 because combining prior art elements according to known methods yields predictable results. The teachings of Bykov and Li rendered obvious a solid pharmaceutical composition comprising nitroxoline as an API, starch as a filler and binder, polyvinylpyrrolidone as a disintegrating agent, and lactose as a filler, in quantities that either encompass or overlap with the ranges recited in the instant application, which is coated in a gastric-soluble coating premix. In view of the teachings of Cheng, an ordinary artisan would be motivated to combine the coating comprising an alginate salt and shellac for a weight gain of 1-10% with the composition rendered obvious above because Cheng teaches this coating to prevent drug “dumping”, which can lead to adverse side effects. A person of ordinary skill in the art would desire their pharmaceutical composition to deliver the API in the intended quantity in the proper portion of the GI tract and would not desire any adverse effects related to drug dumping, and would therefore be motivated to use a coating that can mitigate these potential issues. As a result, there is a reasonable expectation of success in arriving at the invention of claim 8 in view of the teachings of Bykov and Li and further in view of the teachings of Cheng.
Claims 11 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Bykov (Russia Patent No. RU 2149632 C1, published on 27 May 2000) in view of Li (Lubricants 2014, 2 (1), 21.), as applied to claims 1-2, 5, 7, 9-10, 12, 16, and 20 above, and further in view of Grillo et al. (U.S. Patent No. 6,468,561 B1, priority to 30 June 1997, hereafter referred to as Grillo).
Bykov and Li teach the above.
Bykov and Li do not teach the coating to comprise polyethylene glycol (PEG), hydroxypropyl methylcellulose, or lake. This deficiency is offset by the teachings of Grillo.
Grillo teaches aqueous film coatings, which may be applied to solid pharmaceutical tablets or other substrates, which provide improved properties (Title and Abstract). Cellulose polymers, such as hydroxypropyl methylcellulose, are taught to be widely used in pharmaceutical tablet coatings, but difficulties can arise when using cellulosic materials, such as adherence issues, particularly if the matrix comprising the API(s) is waxy (column 1, lines 20-32). In addition, Grillo teaches that sugar is often used for flavor in coatings but efforts are being made to replace sugar to reduce calories and harm to teeth, and that cellulosic polymers meet these needs but tend to “produce coatings that have undesirable taste and mouth-feel” (column 1, lines 33-42).
To meet the goal of a coating with desirable adhesive qualities and taste, low calorie count, and reduced danger to teeth, Grillo teaches aqueous film coatings that are based on polydextrose and may contain additional polymers, plasticizers, colorants and detackifiers (column 1, line 46 - column 2, line 40 and claims 1-2). The additional polymer may be hydroxypropyl methylcellulose, which is taught to be “particularly adapted for coating waxy matrix tablets, which are particularly difficult to coat”, and/or hydroxypropyl cellulose (column 2, lines 42-62, Examples 7-11, and claim 16). The plasticizer is in some embodiments a polyethylene glycol (column 2, line 63, Examples 1-15, and claims 3, 11-12, 22, and 43). Finally, the colorant may be selected from FD&C lakes, D&C lakes, TiO2, or other dyes, and in some embodiments may be FD&C Yellow #5 aluminum lake (column 2, line 66 - column 3, line 3, Examples 3-5, 7, 15, and 17-18, and claims 9, 11-12, 26, 41, and 55). The coating compositions above are taught by Grillo to be “especially effective in coating tablets and the like having debossed or intaglio logos, trademarks, designs or words thereon since it adheres to the tablet surfaces without bridging and obscuring the debossed or intaglio printing” (column 3, lines 11-15).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the filing of the instant application, to combine the coating taught by Grillo with the solid pharmaceutical tablets rendered obvious by the teachings of Bykov and Li to arrive at the invention of claim 14 because combining prior art elements according to known methods yields predictable results. The teachings of Bykov and Li rendered obvious a solid pharmaceutical composition comprising nitroxoline as an API, starch as a filler and binder, polyvinylpyrrolidone as a disintegrating agent, and lactose as a filler, in quantities that either encompass or overlap with the ranges recited in the instant application, which is coated in a gastric-soluble coating premix. In view of the teachings of Grillo, an ordinary artisan would be motivated to combine PEG, hydroxypropyl methylcellulose, and lake with the coating premix taught by Bykov, and replace sugar in the coating of Bykov with polydextrose, because Grillo teaches those coating composition components to reduce the calorie count and damage to teeth of the consumer while improving the adherence to the composition matrix. Further, Grillo teaches that their coating composition allows for logos, designs, or other writing on the exterior of the pharmaceutical tablet, which an ordinary artisan would desire to identify and distinguish their product to consumers.
Although Grillo does not teach hydroxypropyl cellulose to be a disintegrating agent, Grillo does teach its inclusion in the coating above and its properties as a disintegrating agent are necessarily present. See MPEP § 2112.01. “Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.” As a result, there is a reasonable expectation of success in arriving at the invention of claims 11 and 14 in view of the teachings of Bykov and Li and further in view of the teachings of Grillo.
Claims 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Bykov (Russia Patent No. RU 2149632 C1, published on 27 May 2000) in view of Li (Lubricants 2014, 2 (1), 21.), as applied to claims 1-2, 5, 7, 9-10, 12, 16, and 20 above, and further in view of Shim et al. (J. Nat. Canc. Inst. 2010, 102 (24), 1855., hereafter referred to as Shim).
Bykov and Li teach the above.
Bykov and Li do not teach the use of solid pharmaceutical compositions comprising nitroxoline to treat bladder cancer. This deficiency is offset by the teachings of Shim.
Shim teaches the efficacy of nitroxoline in inhibiting angiogenesis and growth of human cancer cells (Abstract). Following high throughput screening of compounds against type 2 methionine aminopeptidase (MetAP2), a protein associated with angiogenesis in tumors, nitroxoline was identified as a promising inhibitor candidate of the angiogenesis and growth of human cancers (pg. 1856 and pg. 1861, Target-Based Screening). Nitroxoline displayed dose-dependent MetAP2 inhibition and endothelial cell proliferation inhibition against human umbilical vein endothelial cells (HUVEC) via assays performed in cell cultures (pg. 1862-1863, Figures 1 and 2). A three-dimensional assay against HUVEC tube formation further demonstrated dose-dependent inhibition by nitroxoline (pg. 1868, Figure 6).
Following successful inhibition in vitro, nitroxoline was analyzed in vivo using mouse models implanted with recombinant mouse vascular endothelial growth factor 164 (VEGF164), human breast tumor xenografts, and human bladder tumor xenografts (pg. 1868-1871). Mice were injected with 60 mg/kg each day, for 7 days following implantation of VEGF164 and 30 days following human breast tumor xenografts, in a vehicle of 5% DMSO in peanut oil (pg. 1860, left column, para. 2 - right column, para. 3). Against both the endothelial growth factor and breast cancer implants, nitroxoline displayed effective inhibition of proliferation and tumor growth (pg. 1868, left column, para. 2 - pg. 1870, right column, para. 1). Mice implanted with bladder cancer tumors were administered nitroxoline in the vehicle described above at a dose of 30 mg/kg/day for 2 weeks and displayed “a statistically significant inhibition of tumor growth compared with the vehicle-treated mice”.
Shim concludes that nitroxoline displays effective “blocking [of] angiogenesis and cancer xenograft growth, particularly in a bladder cancer model” using mouse models (pg. 1871, left column, para. 2). Further, the “efficacy of nitroxoline in inhibiting both angiogenesis and bladder cancer xenograft growth in vivo calls for further preclinical and clinical evaluation of nitroxoline in the treatment of bladder carcinomas” (pg. 1872, left column, para. 1-2).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, in view of the teachings of Shim to use the invention rendered obvious by the teachings of Bykov and Li in a method of treating bladder cancer because using a known active pharmaceutical ingredient in a method to treat a condition it is known to treat produces predictable results. The teachings of Bykov and Li rendered obvious a solid pharmaceutical composition comprising nitroxoline as an API, starch as a filler and binder, polyvinylpyrrolidone as a disintegrating agent, and lactose as a filler, in quantities that either encompass or overlap with the ranges recited in the instant application, which is coated in a gastric-soluble coating premix. In view of the teachings of Shim, one of ordinary skill would be motivated to use the composition above in a method to treat bladder cancer because Shim teaches the API nitroxoline to be effective in treating such a condition. The ordinary artisan would desire an application for their pharmaceutical composition and Shim teaches that the nitroxoline-containing composition would display efficacy in treating bladder cancer. As a result, there is a reasonable expectation of success in arriving at the method of instant claims 17-19 in view of the teachings of Bykov and Li and further in view of the teachings of Shim.
Response to Arguments
The Applicant’s arguments, filed on 10 February 2026, have been fully considered but are not persuasive.
From the para. beginning “First of all” on pg. 7 of the remarks to para. 2 of pg. 8, Applicant argues that the technical problem to be solved by the instant invention is ensuring a moderate rate of dissolution of nitroxoline tablets and avoiding burst release, referencing several sections of the instant specification and directing the reader to Examples 1 and 2. Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The claims are directed to a pharmaceutical composition comprising nitroxoline, methods of preparing the composition, and methods of treatment using the composition.
In response to applicant's arguments against the references individually from para. 3 of pg. 8 to para. 2 of pg. 11, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
From para. 4-5 of pg. 8, Applicant argues that they Bykov reference is directed to a “short-term medication requiring rapid release of active substances” and by analyzing the data disclosed by Bykov, concludes that the reference does not address the same technical problem as the instant invention. Guidelines on analogous and nonanalogous art are provided in MPEP § 2141.01(a). Particularly relevant to this argument is the statement that “A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention)” (bold added for emphasis). The Bykov reference teaches a pharmaceutical composition comprising nitroxoline and a lubricant and is therefore from the same field of endeavor as the instant invention. As a result, Applicant’s argument is not found persuasive.
In the para. that spans the bottom of pg. 8 and top of pg. 9, Applicant argues that because the API nitroxoline has been known in the art since the 1960s and the references used in previous Office Actions “only found that the closest prior art still has the indication for anti-infection purposes” that “seeking a nitroxoline tablet with an appropriate release rate in the anticancer field is a technical challenge that the field has long aspired to solve but has failed to do”. None of these arguments are directed to the rejections under 35 U.S.C. § 103 presented in the previous Office Action and are therefore considered moot.
From para. 2 of pg. 9 to the final para. of pg. 10, Applicant argues that the Li reference does not address the same technical problem as the instant application, that the Li reference does not teach experimental data to motivate an ordinary artisan to replace magnesium stearate with sodium lauryl sulfate to achieve the same technical problem as the instant application, and that because the Li reference teaches “optimal concentration and mixing time are also needed to be taken into consideration when selecting a lubricant”, it would not be obvious to “directly and unambiguously select sodium stearyl fumarate or sodium lauryl sulfate as lubricants for nitroxoline”. Regarding the argument about the same technical problem, Applicant is directed to the response above regarding analogous and nonanalogous art – in brief, the reference is still analogous to the instant invention even if it addresses a different problem in the same field of endeavor. The Li reference is directed to lubricants used in solid pharmaceutical compositions and is therefore analogous to the instant invention.
Regarding the arguments that the specific selection of sodium stearyl fumarate or sodium lauryl sulfate as lubricants would not be motivated, the Examiner respectfully disagrees and directs Applicant to the rejection under 35 U.S.C. § 103 maintained above. In brief, because Li teaches sodium stearyl fumarate to have fewer drawbacks than the more common lubricant magnesium stearate, that its use is appropriate in solid pharmaceutical compositions, and that it is a suitable replacement for magnesium stearate, in addition to the Bykov reference teaching that a lubricant should be used but not teaching a specific species, the teachings of Li would motivate the inclusion of sodium stearyl fumarate. As a result, Applicant’s arguments are found unpersuasive.
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 1-3, 5, 7-12, 14, and 16-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 6 of copending Application No. 17/757,801 in view of Bykov (Russia Patent No. RU 2149632 C1, published on 27 May 2000), Grillo (U.S. Patent No. 6,468,561 B1, priority to 30 June 1997), and Shim (J. Nat. Canc. Inst. 2010, 102 (24), 1855.).
This is a provisional nonstatutory double patenting rejection.
Copending Application No. 17/757,801 recites a pharmaceutical composition in claim 1 that comprises nitroxoline as an API, a filler that may be starch or lactose, a binder than may be hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, or starch, a disintegrant that may be hydroxypropyl cellulose, a lubricant that may be magnesium stearate, sodium stearyl fumarate, or sodium dodecyl sulfate, a glidant that may be silica or talc, and a film coating agent which may be hydroxypropyl methylcellulose and/or PVA. The nitroxoline is recited as being present in an amount of 20-60% w/w based on the total weight of the pharmaceutical composition, the filler is present in an amount 6-180% w/w, the binder is present in an amount of 0-60% w/w, not including 0%, the disintegrant is present in an amount of 0-60% w/w, not including 0%, the lubricant is present in an amount 5x10-4-12% w/w, the glidant is present in an amount of 0-12%w/w, not including 0%, and the coating is present in an amount that results in a 3-15% weight gain (claims 1-4). Claim 6 of ‘801 recites the composition to further comprise an adjuvant, which may be sodium stearyl fumarate and/or sodium dodecyl sulfate, and is present in an amount of 0.5-2.4% w/w.
Copending Application No. 17/757,801 does not recite the pharmaceutical composition coating to comprise TiO2, talc, polyethylene glycol, or lake nor the pharmaceutical composition to be used to treat bladder cancer. These deficiencies are offset by the teachings of Bykov, Grillo, and Shim.
Bykov, Grillo, and Shim are described above.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention recited by ‘801 in view of the teachings of Bykov, Grillo, and Shim to arrive at the invention of instant claims 1-3, 5, 7-12, 14, and 16-20 because combining prior art elements to impart known benefits yields predictable results. Copending application ‘801 recites a pharmaceutical composition that may comprise nitroxoline, sodium dodecyl sulfate, sodium stearyl fumarate, lactose, starch, polyvinylpyrrolidone, and hydroxypropyl methylcellulose in amounts that either encompass or significantly overlap with the ranges recited in the instant application. In view of the teachings of Bykov and Grillo, an ordinary artisan would be motivated to include Ti-O2, talc, PEG, and lake in the coating mixture of the composition recited in ‘801 because Bykov teaches that their coating improves the taste of the composition while maintaining a strong, protective shell that maintains shelf stability for “more than 4 years”, while Grillo teaches the inclusion of polydextrose, PEG, and lake to produce a coating that better adheres to the pharmaceutical composition and allows for logos, designs, or other writing on the exterior of the pharmaceutical composition. One of ordinary skill would desire a strong, shelf-stable coating that properly adheres to the pharmaceutical product and can display an identifiable logo or design to distinguish their product.
In addition, in view of the teachings of Shim, a person of ordinary skill would be motivated to use the invention rendered obvious above in a method of treating bladder cancer because Shim teaches the API nitroxoline to be effective in treating such a condition. The ordinary artisan would desire an application for their pharmaceutical composition and Shim teaches that the nitroxoline-containing composition would display efficacy in treating bladder cancer.
Instant claims 16 and 20 are interpreted as product-by-process claims. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). See MPEP § 2113. The patentability of instant claims 16 and 20 is determined by the product recited in claim 1, which was rendered obvious by the invention recited by copending application no. 17/757,801 and the teachings of Bykov and Grillo, therefore claims 16 and 20 are also prima facie obvious. As a result, there is a reasonable expectation of success in arriving at the invention of claims 1-3, 5, 7-12, 14, and 16-20 in view of the invention recited by copending application 17/757,801 and in view of the teachings of Bykov, Grillo, and Shim.
Claims 1-3, 5, 7-12, 14, and 16-20 are directed to an invention not patentably distinct from claims 1-4 and 6 of commonly assigned copending application no. 17/757,801 in view of Bykov (Russia Patent No. RU 2149632 C1, published on 27 May 2000), Grillo (U.S. Patent No. 6,468,561 B1, priority to 30 June 1997), and Shim (J. Nat. Canc. Inst. 2010, 102 (24), 1855.). Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned copending application no. 17/757,801, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Response to Arguments
In the section titled “Double Patenting” on pg. 11, Applicant argues that because the objections and rejections above should be withdrawn, the nonstatutory double patenting (NSDP) rejection would be the only remaining rejection and should therefore be withdrawn. The Examiner disagrees for at least the reasons detailed above.
A complete response to a NSDP rejection is either a reply by the Applicant showing that the claims subject to the restriction are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional.
Conclusion
No claims are allowed.
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 Sean J. Steinke, Ph.D., whose telephone number is (571) 272-3396. The examiner can normally be reached Mon. - Fri., 09:00 - 17:00 ET.
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/S.J.S./
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619