FINAL DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Receipt is acknowledged of the claim amendments filed on 14 August 2026.
Claims 1-24, 26-33, 35-43 and 68 are cancelled.
Claims 44, 50 and 53 have been amended.
Claims 70-72 have been added.
Claims 25, 34, 55-67 and 69 remains withdrawn from consideration.
Claims 44-54 and 70-72 are examined herein to the extent that the NDMA is the N-nitroso compound, metformin is the active pharmaceutical ingredient, polypropylene is the base polymer, and PEG is the channeling agent, e.g., applicant's elected species.
Claim Interpretation
Claims 70-71 contain the transitional language “consisting essentially of”. For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, “consisting essentially of” will be construed as equivalent to “comprising.” If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of “consisting essentially of,” applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of applicant's invention. PPG Industries Inc. V Guardian Industries Corp. 48 USPQ2d 1351 (Fed. Cir. 1998) and In re De Lajarte 337 F.2d 870, 143 USPQ 256 (CCPA 1964). See MPEP 2111.03.
The instant specification does not define the term “consisting essentially of” in a manner that would allow one skilled in the art to determine what basic and novel characteristics are being materially affected. The specification of the instant application teaches that the entrained polymer is effective in decreasing a rate of formation of or decreasing an amount of N-nitroso compound. This is the same activity described by Mulye and Hakel for their compositions. The addition of ingredients including additional desiccants other than activated carbon and other ingredients including an oxygen scavenger to the entrained polymer for decreasing a rate of formation of or decreasing an amount of N-nitroso compound but does not change or “materially affect” the entrained polymer to decrease a rate of formation of or decreasing an amount of N-nitroso compound. Thus, additional desiccants other than activated carbon and other ingredients including an oxygen scavenger are not excluded from instant claims 70-71.
Rejections Withdrawn
The rejection of claims 44-54 under U.S.C. 112(b), as being indefinite, is withdrawn in view of the claim amendments filed on 14 August 2026.
Rejections Modified and Maintained as Necessitated by the Claim Amendments
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 of this title, 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. 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 44-47, 49-51, 53-54 and 70-72 are rejected under 35 U.S.C. 103 as being unpatentable over MULYE (WO 2022/182778 A1, publication date of 01 September 2022, cited in IDS filed 09/30/2025) in view of HEKAL (US 6,194,079; patent date of 27 February 2001, cited in IDS filed 09/30/2025) and PATEL (US 2021/0380529 A1, publication date of 9 December 2021).
Mulye is primarily directed towards systems and methods for reducing formation of NDMA, using a package that includes a pharmaceutical solid dosage packaging container (abstract).
Regarding claims 44-47, 53-54 and 70-71, Mulye discloses providing pharmaceutical package and method of reducing NDMA (e.g., Nitroso compound contaminant) in pharmaceutical products including Metformin (e.g., for treating a patient having a medical condition with one or more pharmaceutical dosage forms that can form an N-nitroso compound contaminant, having a propensity to form the N-nitroso compound contaminant) (paragraph [00008]). Mulye discloses that a package and method with a type and amount of desiccant for Metformin’s specific drug chemistry to reduce NDMA while also maintaining Metformin’s stability and efficacy (e.g., provide a therapeutically effective amount of drug to the patient for treating the medical condition with improved patient safety by reducing the potential adverse effect associated with the one or more pharmaceutical dosage forms on account of the decrease in the amount of the N-nitroso compound contaminant) (paragraphs [00008] and [00024]). Mulye discloses that N-nitrosdimethylamine (NDMA) is classified as probably carcinogenic to humans by World Health Organization’s (WHO’s) International Agency for Research on Cancer (IARC) (paragraph [00003]). Mulye discloses a pharmaceutical package comprising a pharmaceutical solid dosage packaging container (e.g., enclosure), wherein the pharmaceutical solid dosage packaging container includes one or more desiccants and pharmaceutical product comprising an active ingredient disposed in the container (paragraph [00009]). Mulye discloses that the desiccant includes silica gel and activated carbon (paragraph [00010]). Mulye discloses that forms of desiccant includes particles, grains and powders (paragraph [00047]).
Regarding claim 72, Mulye discloses one or more desiccants (paragraph [00009-00010]) and includes activated charcoal (e.g., activated carbon) (paragraph [00038] and claim 7). Therefore, it would have been prima facie obvious for one of ordinary skill in the art to include only one desiccant and selected activated carbon as the desiccant (e.g., no other desiccant or ingredient including silica gel, a molecular sieve, or oxygen scavenger)
Mulye does not specifically teach an entrained polymer in the headspace that comprises the activated carbon that is dispersed within a base polymer, the entrained polymer being separate and apart from the one or more pharmaceutical dosage forms, opening the enclosure to dispense the one or more pharmaceutical dosage forms and administering the one or more pharmaceutical dosage forms. The deficiencies are cured by the teachings of Hekal and Patel.
Hekal is primarily directed towards a polymer composition having an absorbing material that is entrained within the polymer (see abstract and entire patent).
Regarding claims 44, 47, 49 and 70-71, Hekal teaches a monolithic composition comprising a water-insoluble polymer, a hydrophilic agent and an absorbing material (column 1, lines 15-17). Hekal teaches that application in which moisture absorbing containers are desired include for medications whose efficacy is compromised by moisture (column 1, lines 35-37). Hekal teaches that the initial placement of medicines into a sealed moisture free container is usually controllable but once the medicine is received by the customer, the container must be repeatedly opened and closed to access the medication. Hekal teaches that each time the container is opened and unsealed, moisture bearing air will most likely be introduced into the container and sealed therein upon closure, unless this moisture is removed from the atmosphere or head space of the container. Hekal teaches that it is well known practice to include a desiccating unit together with the medication in the container. (column 1, lines 38-52). Hekal teaches that it is important that the desiccant used not be of a “dusting” nature that may contaminate and compromise the performance of the components in a container. Hekal teaches that it has been recognized as advantageous to expose a desiccating agent to the interior space of containers, while at the same time shielding the components from actual contact with the desiccating material (e.g., being separate and apart from the one or more pharmaceutical dosage forms/ in headspace not occupied by the one or more pharmaceutical dosage forms) (paragraph bridging columns 1 and 2). Hekal teaches composition with interconnecting channels that communicate the entrained absorbing material to appropriate areas of the exterior of the composition in a manner that permits the desired property to migrate from outside the plastic structure to interior locations where the absorbing material is positioned. Hekal teaches that the interconnecting channels are occupied by hydrophilic agents (e.g., channeling agents) that control the transmission rate into the composition that control the transmission rate into the composition (column 2, lines 27-38). Hekal teaches that the composition (e.g., entrained polymer) is in the form of including a liner that is in the interior of a container (e.g., entrained polymer being separate and apart from the one or more pharmaceutical dosage forms/ entrained polymer in headspace not occupied by the one or more pharmaceutical dosage forms) (column 3, lines 1-5; Figure 6). Hekal teaches hydrophilic agents (e.g., channeling agents) combined with a water-insoluble polymer that is used in the formation of shaped articles, wherein the water-insoluble polymer base includes polypropylene (e.g., base polymer) (column 4, lines 4-10). Hekal teaches that suitable hydrophilic agents (e.g., channeling agent) include poly(ethylene glycol) (column 4, lines 54-56). Hekal teaches that the absorbing material includes desiccating compounds (column 5, lines 6-8). Hekal teaches absorbing materials including silica and carbon-based materials including activated charcoal (e.g., activated carbon)(column 5, lines 52-62). Hekal teaches that the “absorbing material” is defined as a particle (column 5, lines 66-67). Hekal teaches a composition with about 68% polypropylene (e.g., base polymer) and 20% of a desiccant (e.g., activated carbon) (column 15, lines 34-39; claim 1).
Regarding claim 72, Hekal teaches that the absorbing material includes one absorbing material (column 1, lines 20-21). Hekal teaches that suitable absorbing materials include activated charcoal (e.g., activated carbon) (column 5, lines 51-62; claim 1). Therefore, it would have been prima facie obvious for one of ordinary skill in the art to include only one absorbing agent and selected activated carbon as the absorbing agent (e.g., no other absorbing agents including silica gel, a molecular sieve, or oxygen scavenger)
Patel is high purity metformin hydrochloride with no detectable amount of N-Nitrosodimethylamine (NDMA) (abstract).
Regarding claim 44, Patel teaches metformin hydrochloride for the treatment of diabetes (paragraph [0002]). Patel teaches administering a therapeutically effective amount of a pharmaceutical composition comprising metformin hydrochloride (paragraph [0038]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to perform a method that comprises providing effective amount of metformin in a solid dosage form that is a part of a package that contains a sealed container that the solid dosage of metformin is contained in, an entrained polymer that is including a liner in an interior of the container (e.g., being separate and apart from the one or more pharmaceutical dosage forms/ in headspace not occupied by the one or more pharmaceutical dosage forms) and comprises a water-insoluble polymer, a hydrophilic agent and a desiccant comprising silica gel and activated carbon; opening and unsealing the container to dispense a solid dosage of metformin; and administering the solid dosage form of metformin to a patient for treating diabetes; wherein the desiccant is in the form of particles, grains and powders; wherein the water-insoluble polymer includes polypropylene (e.g., base polymer); wherein the hydrophilic agent includes poly(ethylene glycol) (e.g., channeling agent); and wherein the desiccant comprising silica gel and activated carbon reduce NDMA while also maintaining Metformin’s stability and efficacy (e.g., for treating a patient having a medical condition with one or more pharmaceutical dosage forms that can form an N-nitroso compound contaminant, having a propensity to form the N-nitroso compound contaminant, provide a therapeutically effective amount of drug to the patient for treating the medical condition with improved patient safety by reducing the potential adverse effect associated with the one or more pharmaceutical dosage forms on account of the decrease in the amount of the N-nitroso compound contaminant). The person of ordinary skill in the art would have been motivated to make those modifications to: 1) allow the desiccating agent to be exposed to the interior space of containers while also shield the desiccant from being in contact with the drug dosage form, by entraining the desiccant of Mulye in the entrained polymer of Hekal; and administered the solid dosage form of Metformin to a patient in order to treat diabetes in the patient as taught by Patel. The person of ordinary skill in the art would have reasonably expected success because Mulye discloses providing pharmaceutical package and method of reducing NDMA (e.g., Nitroso compound contaminant) in pharmaceutical products including Metformin (e.g., for treating a patient having a medical condition with one or more pharmaceutical dosage forms that can form an N-nitroso compound contaminant, having a propensity to form the N-nitroso compound contaminant) (paragraph [00008]). Mulye discloses that a package and method with a type and amount of desiccant for Metformin’s specific drug chemistry to reduce NDMA while also maintaining Metformin’s stability and efficacy (e.g., provide a therapeutically effective amount of drug to the patient for treating the medical condition with improved patient safety by reducing the potential adverse effect associated with the one or more pharmaceutical dosage forms on account of the decrease in the amount of the N-nitroso compound contaminant) (paragraphs [00008] and [00024]). Mulye discloses that the desiccant includes silica gel and activated carbon (paragraph [00010]). Mulye discloses that forms of desiccant includes particles, grains and powders (paragraph [00047]). Hekal teaches a monolithic composition comprising a water-insoluble polymer, a hydrophilic agent and an absorbing material (column 1, lines 15-17). Hekal teaches that application in which moisture absorbing containers are desired include for medications whose efficacy is compromised by moisture (column 1, lines 35-37). Hekal teaches that the initial placement of medicines into a sealed moisture free container is usually controllable but once the medicine is received by the customer, the container must be repeatedly opened and closed to access the medication. Hekal teaches that each time the container is opened and unsealed, moisture bearing air will most likely be introduced into the container and sealed therein upon closure, unless this moisture is removed from the atmosphere or head space of the container. Hekal teaches that it is well known practice to include a desiccating unit together with the medication in the container. (column 1, lines 38-52). Hekal teaches that it is important that the desiccant used not be of a “dusting” nature that may contaminate and compromise the performance of the components in a container. Hekal teaches that it has be recognized as advantageous to expose a desiccating agent to the interior space of containers, while at the same time shielding the components from actual contact with the desiccating material (e.g., being separate and apart from the one or more pharmaceutical dosage forms/ in headspace not occupied by the one or more pharmaceutical dosage forms) (paragraph bridging columns 1 and 2). Patel teaches metformin hydrochloride for the treatment of diabetes (paragraph [0002]). Patel teaches administering a therapeutically effective amount of a pharmaceutical composition comprising metformin hydrochloride (paragraph [0038]).
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill before the effective filing date.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Mulye in view of Hekal and Patel as applied to claims 44-47, 49-51, 53-54 and 70-72 above, and further in view of REZUKE (US 2017/0113203 A1, publication date of 27 April 2017).
Regarding claim 48, the method of claim 44 is described above in section 10.
Mulye, Hekal and Patel do not specifically teach that the activated carbon is a derivative of activated carbon and specifically is tris-activated carbon. The deficiency is made up for by the teachings of Rezuke.
Rezuke is primarily directed towards a filter composition effective in reacting with airborne or gaseous organic impurities that has longer lasting capability of adsorbing organic airborne impurities for a much longer period of time than untreated (abstract).
Regarding claim 48, Rezuke teaches activated carbon impregnated with tris-(hydroxymethyl) aminomethane or TRIS as a means for removing organic and inorganic airborne impurities (paragraph [0019]). Rezuke teaches that activated carbon impregnated with TRIS gives the advantage of using lower basis weight of the composite to achieve removal efficiency equal to or greater than the efficiency of other available products which use a heavier basis weight of activated carbon (paragraph [0043]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to perform a method that comprises providing effective amount of metformin in a solid dosage form that is a part of a package that contains a sealed container that the solid dosage of metformin is contained in, an entrained polymer that is including a liner in an interior of the container (e.g., entrained polymer being separate and apart from the one or more pharmaceutical dosage forms/ entrained polymer in headspace not occupied by the one or more pharmaceutical dosage forms) and comprises a water-insoluble polymer, a hydrophilic agent and a desiccant comprising silica gel and activated carbon; opening and unsealing the container to dispense a solid dosage of metformin; and administering the solid dosage form of metformin to a patient for treating diabetes; wherein the desiccant is in the form of particles, grains and powders; wherein the water-insoluble polymer includes polypropylene (e.g., base polymer); wherein the hydrophilic agent includes poly(ethylene glycol) (e.g., channeling agent); and wherein the desiccant comprising silica gel and activated carbon reduce NDMA while also maintaining Metformin’s stability and efficacy (e.g., for treating a patient having a medical condition with one or more pharmaceutical dosage forms that can form an N-nitroso compound contaminant, having a propensity to form the N-nitroso compound contaminant, provide a therapeutically effective amount of drug to the patient for treating the medical condition with improved patient safety by reducing the potential adverse effect associated with the one or more pharmaceutical dosage forms on account of the decrease in the amount of the N-nitroso compound contaminant); and wherein the activated carbon is activated carbon impregnated with tris-(hydroxymethyl) aminomethane (TRIS). The person of ordinary skill in the art would have been motivated to make those modifications to obtain a method with increased efficacy in reducing NDMA (e.g., organic impurity) by substituting activated carbon impregnated with tris-(hydroxymethyl) aminomethane (TRIS) that is taught by Rezuke. The person of ordinary skill in the art would have reasonably expected success because Rezuke is a filter composition effective in reacting with airborne or gaseous organic impurities that has longer lasting capability of adsorbing organic airborne impurities for a much longer period of time than untreated (abstract). Rezuke teaches that activated carbon impregnated with TRIS gives the advantage of using lower basis weight of the composite to achieve removal efficiency equal to or greater than the efficiency of other available products which use a heavier basis weight of activated carbon (paragraph [0043]).
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill before the effective filing date.
Claim 52 is rejected under 35 U.S.C. 103 as being unpatentable over Mulye in view of Hekal and Patel as applied to claims 44-47, 49-51, 53-54 and 70-72 above, and further in view of VOELLMICKE (WO 2020/214632 A1, publication date of 22 October 2020, cited in IDS filed 09/30/2025).
Regarding claim 52, the method of claim 44 is described above in section 10.
Regarding claim 52, Hekal teaches that the entrained polymer composition is in the form of including films made by a thermal extrusion process (abstract; paragraph bridging columns 6 and 7; claim 13).
Mulye, Hekal and Patel do not specifically teach that the entrained polymer as a film has a thickness of from 0.1 to 1.2 mm. The deficiency is made up for by the teachings of Voellmicke.
Voellmicke is primarily directed towards a polymer composition comprising activated carbon that is used for sorption of formaldehyde from air, gas or liquids (abstract).
Regarding claim 52, Voellmicke teaches polymer composition comprising a base polymer, activated carbon and channeling agent (paragraph [0011]). Voellmicke teaches polymer composition formed by including extrusion to form including a film and the polymer composition is incorporated into a packaging material (paragraph [0012]). Voellmicke teaches that the polymer comprises polypropylene as the base polymer (paragraph [0013]). Voellmicke teaches the polymer composition is an entrained polymer composition comprising activated carbon uniformly distributed within the base polymer (paragraph [0042]). Voellmicke teaches that the entrained polymer as a film has a thickness of from 0.1 mm to 1.0 mm (paragraph [0059]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to perform a method that comprises providing effective amount of metformin in a solid dosage form that is a part of a package that contains a sealed container that the solid dosage of metformin is contained in, an entrained polymer that is including a film in an interior of the container (e.g., entrained polymer being separate and apart from the one or more pharmaceutical dosage forms/ entrained polymer in headspace not occupied by the one or more pharmaceutical dosage forms) and comprises a water-insoluble polymer, a hydrophilic agent and a desiccant comprising silica gel and activated carbon; opening and unsealing the container to dispense a solid dosage of metformin; and administering the solid dosage form of metformin to a patient for treating diabetes; wherein the desiccant is in the form of particles, grains and powders; wherein the water-insoluble polymer includes polypropylene (e.g., base polymer); wherein the hydrophilic agent includes poly(ethylene glycol) (e.g., channeling agent); wherein the desiccant comprising silica gel and activated carbon reduce NDMA while also maintaining Metformin’s stability and efficacy (e.g., for treating a patient having a medical condition with one or more pharmaceutical dosage forms that can form an N-nitroso compound contaminant, having a propensity to form the N-nitroso compound contaminant, provide a therapeutically effective amount of drug to the patient for treating the medical condition with improved patient safety by reducing the potential adverse effect associated with the one or more pharmaceutical dosage forms on account of the decrease in the amount of the N-nitroso compound contaminant); and wherein the film has a thickness of from 0.1 mm to 1.0 mm. The person of ordinary skill in the art would have been motivated to make those modifications because Hekal teaches forms of entrain polymer including a film, and Voellmicke teaches substantially the same entrained polymer that can be in the form of films that have a thickness of from 0.1 mm to 1.0 mm, which a person of ordinary skill in the art would expect can be substituted as a suitable entrained polymer form, especially in the absence of evidence to the contrary. The person of ordinary skill in the art would have reasonably expected success because Hekal teaches that the entrained polymer composition is in the form of including films made by a thermal extrusion process (abstract; paragraph bridging columns 6 and 7; claim 13). Voellmicke teaches polymer composition comprising a base polymer, activated carbon and channeling agent (paragraph [0011]). Voellmicke teaches polymer composition formed by including extrusion to form including a film and the polymer composition is incorporated into a packaging material (paragraph [0012]). Voellmicke teaches that the polymer comprises polypropylene as the base polymer (paragraph [0013]). Voellmicke teaches the polymer composition is an entrained polymer composition comprising activated carbon uniformly distributed within the base polymer (paragraph [0042]). Voellmicke teaches that the entrained polymer as a film has a thickness of from 0.1 mm to 1.0 mm (paragraph [0059]).
Thus, the claimed invention as a whole is clearly prima facie obvious over the teachings of the prior art.
Response to Arguments
Applicant argues that Mulye teaches desiccant in sachet or canister which would provide direct fluid exposure between the desiccant and the package environment to allow the desiccant to readily scavenge impurities such as NDMA in the package. Applicant argues that the person of ordinary skill in the art would not be motivated to blend such desiccant into an “entrained polymer” because the person of ordinary skill in the art would expect that encapsulating the desiccant within a barrier material, such as a polymer, would inhibit the nitrosamine mitigating effect of the desiccant, resulting in performance that is inferior to desiccant in a porous sachet or canister with gas permeable ends.
Applicant's arguments filed on 14 August 2026 have been fully considered but they are not persuasive. In response, Mulye discloses providing pharmaceutical package and method of reducing NDMA (e.g., Nitroso compound contaminant) in pharmaceutical products including Metformin (e.g., for treating a patient having a medical condition with one or more pharmaceutical dosage forms that can form an N-nitroso compound contaminant, having a propensity to form the N-nitroso compound contaminant) (paragraph [00008]). Mulye discloses that a package and method with a type and amount of desiccant for Metformin’s specific drug chemistry to reduce NDMA while also maintaining Metformin’s stability and efficacy (e.g., provide a therapeutically effective amount of drug to the patient for treating the medical condition with improved patient safety by reducing the potential adverse effect associated with the one or more pharmaceutical dosage forms on account of the decrease in the amount of the N-nitroso compound contaminant) (paragraphs [00008] and [00024]). Mulye discloses a pharmaceutical package comprising a pharmaceutical solid dosage packaging container (e.g., enclosure), wherein the pharmaceutical solid dosage packaging container includes one or more desiccants and pharmaceutical product comprising an active ingredient disposed in the container (paragraph [00009]). Mulye discloses that the desiccant includes activated carbon (paragraph [00010]). Hekal teaches a monolithic composition comprising a water-insoluble polymer, a hydrophilic agent and an absorbing material (column 1, lines 15-17). Hekal teaches that application in which moisture absorbing containers are desired include for medications whose efficacy is compromised by moisture (column 1, lines 35-37). Hekal teaches that the initial placement of medicines into a sealed moisture free container is usually controllable but once the medicine is received by the customer, the container must be repeatedly opened and closed to access the medication. Hekal teaches that each time the container is opened and unsealed, moisture bearing air will most likely be introduced into the container and sealed therein upon closure, unless this moisture is removed from the atmosphere or head space of the container. Hekal teaches that it is well known practice to include a desiccating unit together with the medication in the container (column 1, lines 38-52). Hekal teaches that it is important that the desiccant used not be of a “dusting” nature that may contaminate and compromise the performance of the components in a container. Hekal teaches that it has be recognized as advantageous to expose a desiccating agent to the interior space of containers, while at the same time shielding the components from actual contact with the desiccating material (e.g., being separate and apart from the one or more pharmaceutical dosage forms/ in headspace not occupied by the one or more pharmaceutical dosage forms) (paragraph bridging columns 1 and 2). Hekal teaches that the composition (e.g., entrained polymer) is in the form of including a liner that is in the interior of a container (e.g., entrained polymer being separate and apart from the one or more pharmaceutical dosage forms/ entrained polymer in headspace not occupied by the one or more pharmaceutical dosage forms) (column 3, lines 1-5; Figure 6). Hekal teaches hydrophilic agents (e.g., channeling agents) combined with a water-insoluble polymer that is used in the formation of shaped articles, wherein the water-insoluble polymer base includes polypropylene (e.g., base polymer) (column 4, lines 4-10). Hekal teaches that the absorbing material includes desiccating compounds (column 5, lines 6-8). Hekal teaches absorbing materials including silica and carbon-based materials including activated charcoal (e.g., activated carbon)(column 5, lines 52-62). Hekal teaches that the “absorbing material” is defined as a particle (column 5, lines 66-67). Hekal teaches a composition with about 68% polypropylene (e.g., base polymer) and 20% of a desiccant (e.g., activated carbon) (column 15, lines 34-39; claim 1). Thus, it would have been prima facie obvious for one of ordinary skill in the art to use the entrained polymer of Hekal as the material to reduce NDMA while also maintaining Metformin’s stability and efficacy in the pharmaceutical package of Mulye obtain advantages including using desiccant not of “dusting” nature that may contaminate and compromise the performance of the components (e.g., pharmaceutical dosage form) in a container and where the absorption capacity of the desiccant is potentiated by exposing it exclusively to the interior of the package from which it is desired that the vapor be withdrawn and retained therefrom.
Further, Applicant did not provide any factual evidence including a desiccant in an “entrained polymer” would inhibit the nitrosamine mitigating effect. Applicant’s mere opinion without factual evidence is not persuasive.
Applicant argues that the skilled artisan would likely expect the base polymer of the entrained polymer to block the nitrosamine mitigating activity of the activated carbon, due to the barrier properties of the base polymer.
In response, Hekal teaches that there are interconnecting channels that communicate the entrained absorbing material (e.g., activated carbon) to the appropriate areas of the exterior of the composition in a manner that permits the desired property to migrate from outside the plastic structure to interior locations where the absorbing material is positioned (column 2, lines 27-34). Therefore, one of ordinary skill in the art would expect activated carbon entrained in the base polymer would be have nitrosamine mitigating activity when entrained in the base polymer of Hekal.
Additionally, Applicant’s mere opinion without factual evidence is not persuasive.
Applicant argues that the instant application surprisingly illustrate that activated carbon in entrained polymer film format adsorb nitrosamines such as NDMA more effectively than the corresponding raw active on an equal mass basis. Applicant points to including Examples 5 and 6, where the comparison of Example 6 with Example 5 shows that tris-activated carbon in film format absorbs NDMA more effectively than the corresponding raw active. Applicant argues that the result is surprising and unexpected because the skilled person would expect that raw active that is not surrounded by a barrier material such as polymer, would be more effective since it has direct (unimpeded) access to the package environment.
In response, Example 6 includes tris-activated carbon in a film which is made of resin-3040 (e.g., Example 1). The data based on the experimental procedure detailed in Examples 5 and 6 of the instant specification, is not commensurate in scope with the instant claims because the film in Example 6 is made of specifically resin-3040 and there is no nexus provided that shows that other materials that make up the film which are included by the instant claims or polypropylene (e.g., elected species) would provide the same results.
Additionally, Applicant has not demonstrated that the difference between 26% and 10.26% is reproducible and falls outside the ordinary variation expected during experimentation. See McNeil-PPC, Inc. v. L. Perrigo Co., 337 F3d 1362, 1370 (Fed. Cir.2003) (Finding evidence unpersuasive that “was based on the results of a study involving only nine participants and thus did not rise to the level of statistical significance” and finding the studies were “not shown to be reproducible”).
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Thus, for the reasons of record and for the reasons presented above claims 44-54 and 70-72 are rejected under 35 U.S.C. 103(a).
Conclusion and Correspondence
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 extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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/JOHN P NGUYEN/
Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600
