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 .
Priority
This application is a continuation of U.S. Application No. 16/411,861 filed on May 14, 2019 now U.S. Patent No. 11,534,416 which is a division of U.S. Patent No. 14/441,317 filed on October 21, 2016, now U.S. Patent No. 10,420,737 which is a national stage entry of PCT/CN2013/087049 filed on November 13, 2013.
Response to Amendment
No amendments to the claims were made by Applicant’s response filed on March 30, 2026. Claims 1-23 are currently pending and presented for examination.
Response to Arguments
Applicant's arguments filed March 30, 2026 have been fully considered but they are not persuasive.
With respect to the rejection under 35 USC 112(a) Applicant argues that although the phrase “an active ingredient” is not explicitly recited in the present specification, one of ordinary skill in the art would recognize that mannitol, sucralose, and any combination thereof are acting as active ingredients in view of the present specification and specifically the examples. Applicant argues that claim amendments can be supported by implicit or inherent disclosure.
These arguments are found not persuasive since nowhere in the instant specification are mannitol, sucralose or any combination thereof referred to as active ingredients. Throughout the specification these compounds are referred to as excipients within formulations containing acetaminophen. The specification does not teach or suggest that mannitol, sucralose, or combinations thereof are anything other than excipients. Excipients are usually considered inactive substances formulated alongside active ingredients such as fillers, binders, lubricants, disintegrants, etc. For example, page 1 of the specification states “a new hepatotoxicity-free pharmaceutical composition containing acetaminophen (APAP), in particular, a new pharmaceutical composition that contains a combination of acetaminophen and one or any combinations of common and pharmaceutically acceptable excipients.” In addition, Tables 2 and 3 on pages 16-23 list the compounds as excipients. Moreover, Applicant specifically states on page 24 of the specification, “In conclusion, the invention not only provides a novel application of acetaminophen but also reduces hepatotoxicity caused by acetaminophen by combination use of acetaminophen with common and safe excipients.” Thus based on the instant specification, a person of ordinary skill in the art would recognize that the active ingredient in the composition is acetaminophen and that the invention is drawn to an acetaminophen formulation comprising acetaminophen as the active ingredient combined with common excipients well known in the art. Since there is no definition of excipient found in the instant specification, the plain ordinary meaning is given which is an inactive substance that serves as the vehicle or medium for a drug or other active substance, i.e. an inactive pharmaceutical ingredient (not the active drug) included in a medicine to perform specific functions, such as acting as a binder, filler, lubricant, coating agent, coloring agent, or disintegrant.
For these reasons, the previous rejection under 35 USC 112(a) is hereby maintained and reproduced below.
With respect to the rejection under 35 U.S.C. § 112(b) Applicant argues that although claims 1 and 11 recite the closed language "consisting of" in a Markush group, claims 1 and 11 also use the open language "comprising" as a transitional phrase after the preamble and thus, the claim is open to additional elements.
These arguments are found not persuasive because when the phrase "consists of" appears in a clause of the body of a claim, said claim term set off with ‘consisting of’ is closed to unrecited elements." Multilayer Stretch Cling Film Holdings, Inc. v. Berry Plastics Corp., 831 F.3d 1350, 1359, 119 USPQ2d 1773, 1781 (Fed. Cir. 2016) (a layer "selected from the group consisting of" specific resins is closed to resins other than those listed). In the instant case, the claim term set off with ‘consisting of’ is the group consisting of mannitol, sucralose and any combination thereof. Thus the group consisting of mannitol, sucralose and any combination thereof is closed to unrecited elements. Therefore a claim which depends from a claim which "consists of" the recited elements or steps cannot add an additional element or step. The transitional term “comprising” in the preamble of the claim is inclusive or open-ended and does not exclude additional, unrecited method steps. The transition ‘comprising’ in a method claim indicates that the claim is open-ended and allows for additional steps. Thus the claim may include additional method steps. However, claims 4, 13, 14 and 23 recite the compound (and not the method), which in claim 1 is closed to unrecited elements, contains menthol, etc. which are not recited in claim 1. Thus claims 4, 13, 14 and 23 are properly rejected under 35 USC 112(b) and therefore said rejection is hereby maintained and reproduced below.
With respect to the rejection under 35 USC 102(a)(1) over Moe et al., Applicant argues that the claimed invention is directed to a method for reducing liver damage caused by acetaminophen (APAP) by administering to a subject in need thereof a compound selected from the group consisting of mannitol, sucralose and any combination thereof, as an active ingredient, in an amount effective in reducing liver damage caused by APAP (claim 1), and a method for administering acetaminophen (APAP) to a subject in need thereof by administering to the subject acetaminophen and a compound, as an active ingredient, in an amount effective in reducing liver damage caused by APAP, wherein the compound is selected from the group consisting of mannitol, sucralose and any combination thereof (claim 11). Applicant argues that in contrast, Moe discloses orally dissolved/disintegrable dosage forms adapted for direct oral dosing. However, Moe does not disclose that the dosage form described therein will reduce liver damage caused by APAP. Moe fails to disclose a compound selected from the group consisting of mannitol, sucralose and any combination thereof as an active ingredient for reducing liver damage caused by APAP. Thus, Applicant argues that the claimed invention is not anticipated by Moe since the reference does not teach or provide for each of the limitations recited in the pending claims.
These arguments are found not persuasive for reasons of record.
The rejected claims of the instant application claim a method for reducing liver damage caused by acetaminophen (APAP) comprising administering a compound to a subject in need thereof wherein the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof as an active ingredient, in an amount effective in reducing liver damage caused by APAP as well as a method for administering acetaminophen to a subject in need thereof comprising administering to the subject acetaminophen and a compound as an active ingredient, in an amount effective in reducing liver damage caused by APAP, wherein the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof. Moreover, the instant specification describes the instant invention as new hepatotoxicity-free pharmaceutical composition containing acetaminophen (APAP), in particular, a new pharmaceutical composition that contains a combination of acetaminophen and one or any combinations of common and pharmaceutically acceptable excipients that can inhibit the activity of P450 2E1 (CYP2E1) to reduce hepatotoxicity induced by acetaminophen (page 1). Furthermore the instant specification teaches that the APAP composition of the instant invention reduces hepatotoxicity caused by acetaminophen by combination use of acetaminophen with common and safe excipients (page 24). Thus the instant invention relates to the administration of a formulation comprising acetaminophen and one or more excipients such as mannitol, sucralose and combinations thereof to a subject in need thereof wherein the administration of said formulation with the claimed excipients has the added benefit of reducing liver damage caused by acetaminophen. Therefore any prior art which teaches administering an APAP formulation containing the claimed excipients will inherently have the same effect as claimed which is reducing liver damage caused by acetaminophen.
Moe et al. specifically teaches administering a formulation for tableting by direct compression comprising paracetamol (acetaminophen, APAP), 325.42 mg/tab of mannitol, 175.50 mg/tab of microcrystalline cellulose, crospovidone, 19.50 mg/tab magnesium stearate, 15.60 mg/tab citric acid, and 10.40 mg/tab sucralose (pages 24-26 [0057]-[0059], examples 1, 3 and 4). As defined on pages 5-6 of the instant specification, an amount effective in reducing liver damage caused by APAP is interpreted as the amount of microcrystalline cellulose is 100-1000 mg, the amount of mannitol is 10-250 mg, the amount of sucralose is 10-250 mg, the amount of Eudragit® S100 is 0.17-5.5 g, the amount of Pluronic® F68 is 1.4-5.5 g, the amount of menthol is 8-34 mg.
Thus, the cited claims of the instant application are anticipated since Moe et al. specifically teaches administration of an acetaminophen dosage form comprising one or more compounds that reduce liver damage caused by acetaminophen including mannitol and sucralose. Moreover, Moe et al. specifically teaches that the dosage of acetaminophen contains amounts effective in reducing liver damage caused by APAP including 10.40 mg/tab sucralose.
Therefore, the method of Moe et al. which comprises administering a compound to a subject in need thereof wherein the compound is sucralose in an amount effective in reducing liver damage caused by APAP will inherently reduce liver damage caused by acetaminophen (APAP) wherein the liver damage includes necrosis or vacuolization of the liver.
In response to applicant's argument that Moe does not disclose that the dosage form described therein will reduce liver damage caused by APAP, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
In addition, it is not necessary that the prior art suggests the same advantage or result discovered by applicant when the steps of the claim are the same as those described or suggested by the prior art. See, e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323 (Fed. Cir. 2005) (“One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.”); In re Lintner, 458 F.2d 1013 (CCPA 1972); In re Dillon, 919 F.2d 688 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). Here, Moe teaches administering a dosage from comprising acetaminophen and a compound selected from sucralose, mannitol and combinations thereof. Therefore, the administration of acetaminophen with a compound selected from sucralose, mannitol and combinations thereof as taught by Moe will necessarily result in a reduction in liver damage caused by acetaminophen. The mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Prindle, 297 F.2d 251, 254 (CCPA 1962). Here, the latent property identified by Applicant is the reduction of liver damage caused by acetaminophen which will inherently occur by practicing the invention of Moe and administering the composition disclosed therein.
For these reasons, the previous anticipation rejection over Moe et al. is hereby maintained and reproduced below.
Applicant’s arguments with respect to the rejection under 35 USC 102(a)(1) over Elphick are found not persuasive for the same reasons as detailed above for Moe et al.
The cited claims of the instant application are anticipated since Elphick et al. specifically teaches an acetaminophen dosage for administration for the treatment of pain comprising one or more compounds that reduce liver damage caused by acetaminophen including hydroxypropyl cellulose and mannitol and further comprising a polyoxyethylene-polyoxypropylene block copolymer (Pluronic® F127). Moreover, Elphick et al. specifically teaches amounts effective in reducing liver damage caused by APAP including 100 and 200 mg mannitol. Therefore, administration of a disclosed formulation of Elphick et al. which comprises mannitol in an amount effective in reducing liver damage caused by APAP will inherently reduce liver damage caused by acetaminophen (APAP) wherein the liver damage includes necrosis or vacuolization of the liver. Elphick et al. specifically teaches the administration of mannitol in an amount effective in reducing liver damage caused by APAP as disclosed in the instant application and thus administration of the dosage form of Elphick et al. will inherently reduce the formation of NAPQI from acetaminophen as claimed in the instant claims.
In response to applicant's argument that Elphick et al. does not disclose that the dosage form described therein will reduce liver damage caused by APAP, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
In addition, it is not necessary that the prior art suggests the same advantage or result discovered by applicant when the steps of the claim are the same as those described or suggested by the prior art. See, e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323 (Fed. Cir. 2005) (“One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.”); In re Lintner, 458 F.2d 1013 (CCPA 1972); In re Dillon, 919 F.2d 688 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). Here, Elphick et al. teaches administering a dosage from comprising acetaminophen and a compound selected from sucralose, mannitol and combinations thereof. Therefore, the administration of acetaminophen with a compound selected from sucralose, mannitol and combinations thereof as taught by Elphick et al. will necessarily result in a reduction in liver damage caused by acetaminophen. The mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Prindle, 297 F.2d 251, 254 (CCPA 1962). Here, the latent property identified by Applicant is the reduction of liver damage caused by acetaminophen which will inherently occur by following the teachings of Elphick and administering the formulation disclosed therein.
For these reasons, the previous anticipation rejection over Elphick et al. is hereby maintained and reproduced below.
With respect to the rejection under 35 USC 103, Applicant argues that Moe does not disclose that the dosage form described therein will reduce liver damage caused by APAP and fails to disclose or suggest a resolution such as administering a compound for reducing liver damage caused by APAP. Applicant argues that absent such suggestions, one of ordinary skill in the art would have no proper reason, rationale, or motivation, with a reasonable expectation of success, to choose mannitol, sucralose and any combination thereof as an active ingredient for reducing liver damage caused by APAP in view of Moe. Applicant further argues that Lee and Hu do not overcome the deficiencies of Moe since Lee discloses the role of CYP2E1 in the hepatotoxicity of acetaminophen and Hu demonstrates that sucralose, mannitol, and microcrystalline cellulose are excipients used in pharmaceutical formulations that inhibit CYP2E1; however, Lee and Hu neither disclose nor suggest that mannitol, sucralose and any combination thereof can be used as an active ingredient for reducing liver damage caused by APAP. Applicant further argues as shown in Tables 2 and 3 in the present specification, Tween 20 exhibits a higher CYP2E1 inhibitory activity (80.6+1.9 and 55.4+1.9, 16.5 UM) as compared with mannitol with a lower CYP2E1 inhibitory activity (40.9+2.8, 44.8+1.8, 16.5 UM) and sucralose with a lower CYP2E1 inhibitory activity (41.142.7, 37.142.8, 16.5 uM). However, Tween 20 shows no protective effect in reducing hepatotoxicity of APAP as evidenced by the previously provided Kelava et al. Thus, Applicant argues that one of ordinary skill in the art from Moe alone or in combination with Lee and/or Hu would not be motivated with reasonable expectation of success to choose mannitol, sucralose and any combination thereof as an active ingredient for reducing liver damage caused by APAP.
These arguments are found not persuasive for the reasons detailed above. The claims of the instant application recite administering acetaminophen with one or more of mannitol and sucralose for reducing liver damage caused by acetaminophen. Moe et al. specifically teaches administering acetaminophen with one or more of mannitol and sucralose and moreover, specifically teaches an amount of sucralose as disclosed in the instant specification that reduces liver damage caused by acetaminophen. Furthermore, Lee et al. and Hu et al. specifically teach a positive correlation between CYP2E1 inhibitory activity and reduction of hepatotoxicity caused by APAP. Lee et al. teaches that CYP2E1 mediates hepatotoxicity of acetaminophen and that inhibition of CYP2E1 protects against liver toxicity induced by high dosages of acetaminophen (see abstract, pages 12066-12067 and Figure 5), and Hu et al. teaches that mannitol in an amount of 10 mg or more will inhibit CYP2E1 and thus one would expect the amount of mannitol taught in Moe et al. which is more than 10 mg to inhibit CYP2E1 and thus reduce liver damage caused by acetaminophen.
Thus Applicant’s arguments that one of ordinary skill in the art from Moe alone or in combination with Lee and/or Hu would not be motivated with reasonable expectation of success to choose mannitol, sucralose and any combination thereof as an active ingredient for reducing liver damage caused by APAP is found not persuasive since an ordinary skilled artisan following the teachings of Moe would not have to be motivated to select mannitol, sucralose and combinations thereof since Moe et al. specifically teaches including mannitol and sucralose in the dosage form comprising acetaminophen. Thus by following the teachings of Moe et al. and administering the dosage form comprising acetaminophen, mannitol and sucralose, the same effects of reducing liver damage caused by APAP as claimed will necessarily occur. Therefore, Applicant’s data as argued does not overcome the rejection of record since the rejection of record is not based on the selection of mannitol or sucralose since Moe et al. specifically teaches including mannitol and sucralose in the formulation in amounts that will reduce liver damage caused by APAP as claimed.
Applicant’s arguments with respect to the rejection under 35 USC 103 over Elphick et al. in view of Lee and Hu are found not persuasive for the same reasons as detailed above for Moe et al. in view of Lee and Hu.
Elphick et al. specifically teaches administering acetaminophen with one or more of mannitol and sucralose and moreover, specifically teaches an amount of mannitol as disclosed in the instant specification that reduces liver damage caused by acetaminophen. Furthermore, Lee et al. teaches that CYP2E1 mediates hepatotoxicity of acetaminophen and that inhibition of CYP2E1 protects against liver toxicity induced by high dosages of acetaminophen (see abstract, pages 12066-12067 and Figure 5), and Hu et al. teaches that mannitol in an amount of 10 mg or more will inhibit CYP2E1 and thus one would expect the amount of mannitol taught in Elphick et al. which is more than 10 mg to inhibit CYP2E1 and thus reduce liver damage caused by acetaminophen.
Thus Applicant’s arguments that one of ordinary skill in the art from Elphick alone or in combination with Lee and/or Hu would not be motivated with reasonable expectation of success to choose mannitol, sucralose and any combination thereof as an active ingredient for reducing liver damage caused by APAP is found not persuasive since an ordinary skilled artisan following the teachings of Elphick would not have to be motivated to select mannitol, sucralose and combinations thereof since Elphick et al. specifically teaches including mannitol in the dosage form comprising acetaminophen. Thus by following the teachings of Elphick et al. and administering the dosage form comprising acetaminophen and mannitol, the same effects of reducing liver damage caused by APAP as claimed will necessarily occur. Therefore, Applicant’s data as argued does not overcome the rejection of record since the rejection of record is not based on the selection of mannitol or sucralose since Elphick et al. specifically teaches including mannitol in the formulation in amounts that will reduce liver damage caused by APAP as claimed.
For these reasons, the previous rejections under 35 USC 103 are hereby maintained and reproduced below.
This action is FINAL.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-23 of the instant application claim a method for reducing liver damage caused by acetaminophen (APAP) comprising administering a compound to a subject in need thereof wherein the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof as an active ingredient, in an amount effective in reducing liver damage caused by APAP as well as a method for administering acetaminophen to a subject in need thereof comprising administering to the subject acetaminophen and a compound as an active ingredient in an amount effective in in reducing liver damage caused by APAP, wherein the compound selected from the group consisting of mannitol, sucralose, and any combination thereof.
The claims recite the limitation “an active ingredient.” There is no disclosure in the instant specification of an active ingredient. The specification does not describe any compound as an active ingredient. Moreover the specification does not describe what is meant by an active ingredient. Thus said newly added limitation is new matter.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4, 13, 14 and 23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
When the phrase "consists of" appears in a clause of the body of a claim, said claim term set off with ‘consisting of’ is closed to unrecited elements." Multilayer Stretch Cling Film Holdings, Inc. v. Berry Plastics Corp., 831 F.3d 1350, 1359, 119 USPQ2d 1773, 1781 (Fed. Cir. 2016) (a layer "selected from the group consisting of" specific resins is closed to resins other than those listed). A claim which depends from a claim which "consists of" the recited elements or steps cannot add an element or step.
Claim 4 recites the limitation "optionally menthol". There is insufficient antecedent basis for this limitation in the claim since claim 1 from which claim 4 depends claims administering to a subject in need thereof a compound selected from the group consisting of mannitol, sucralose, and any combination thereof. Thus claim 1 recites the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof, and does not have an option for selecting menthol as claimed in claim 4.
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Claim 13 recites the limitation " wherein the compound further includes an additional compound selected from the group consisting of menthol, poly(methacrylic acid- methyl methacrylate), polyoxyethylene-polyoxypropylene block copolymer and any combination thereof." There is insufficient antecedent basis for this limitation in the claim since claim 11 from which claim 13 depends claims administering to a subject in need thereof a compound selected from the group consisting of mannitol, sucralose, and any combination thereof. Thus claim 11 recites the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof, and does not have an option for selecting an additional compound selected from the group consisting of menthol, poly(methacrylic acid- methyl methacrylate), polyoxyethylene-polyoxypropylene block copolymer and any combination thereof as claimed in claim 13.
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Claim 14 recites the limitation "optionally menthol". There is insufficient antecedent basis for this limitation in the claim since claim 11 from which claim 14 depends claims administering to a subject in need thereof a compound selected from the group consisting of mannitol, sucralose, and any combination thereof. Thus claim 11 recites the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof, and does not have an option for selecting menthol as claimed in claim 14.
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Claim 23 recites the limitation " wherein the compound further includes polyoxyethylene-polyoxypropylene block copolymer." There is insufficient antecedent basis for this limitation in the claim since claim 1 from which claim 23 depends claims administering to a subject in need thereof a compound selected from the group consisting of mannitol, sucralose, and any combination thereof. Thus claim 1 recites the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof, and does not have an option for selecting polyoxyethylene-polyoxypropylene block copolymer as claimed in claim 23.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 5, 9-12, 15, 19 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Moe et al. WO 2007/050631 A2 (Provided on IDS).
Claims 1-2, 5, 9-12, 15, 19 and 20 of the instant application claim a method for reducing liver damage caused by acetaminophen (APAP) comprising administering a compound to a subject in need thereof wherein the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof as an active ingredient, in an amount effective in reducing liver damage caused by APAP as well as a method for administering acetaminophen to a subject in need thereof comprising administering to the subject acetaminophen and a compound as an active ingredient in an amount effective in in reducing liver damage caused by APAP, wherein the compound selected from the group consisting of mannitol, sucralose, and any combination thereof.
As defined on pages 5-6 of the instant specification an amount effective in reducing liver damage caused by APAP is interpreted as the amount of microcrystalline cellulose is 100-1000 mg, the amount of mannitol is 10-250 mg, the amount of sucralose is 10-250 mg, the amount of Eudragit® S100 is 0.17-5.5 g, the amount of Pluronic® F68 is 1.4-5.5 g, the amount of menthol is 8-34 mg.
Please note that “In determining whether the invention as a whole would have been obvious under 35 U.S.C. 103, we must first delineate the invention as a whole. In delineating the invention as a whole, we look not only to the subject matter which is literally recited in the claim in question... but also to those properties of the subject matter which are inherent in the subject matter and are disclosed in the specification. . . Just as we look to a chemical and its properties when we examine the obviousness of a composition of matter claim, it is this invention as a whole, and not some part of it, which must be obvious under 35 U.S.C. 103.” In re Antonie, 559 F.2d 618, 620, 195 USPQ 6,8 (CCPA 1977). See also Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993) (The Board rejected a claim directed to a method for protecting a plant from plant pathogenic nematodes by inoculating the plant with a nematode inhibiting strain of P. cepacia. A U.S. patent to Dart disclosed inoculation using P. cepacia type Wisconsin 526 bacteria for protecting the plant from fungal disease. Dart was silent as to nematode inhibition but the Board concluded that nematode inhibition was an inherent property of the bacteria. The Board noted that applicant had stated in the specification that Wisconsin 526 possesses an 18% nematode inhibition rating.).
Moe et al. teaches orally dissolvable/disintegrable dosage forms adapted for direct oral dosing (abstract). Moe et al. teaches an orally dissolved/disintegrable tablet adapted for direct oral dosing comprising acetaminophen [0014]. Moe et al. teaches that the dosage form, caplet or tablet may be stored in bulk, for example drums, bulk bins, hoppers, and/or packed in conventional openable and reclosable multi-tablet bottles, or other similar packaging [0015]. Moe et al. teaches that disintegration means that the dosage form falls apart into smaller particles and/or aggregates and portions will begin to dissolve when the dosage form is placed in the mouth and preferably on the tongue [0018].
Moe et al. specifically teaches a formulation for tableting by direct compression comprising paracetamol (acetaminophen, APAP), 325.42 mg/tab of mannitol, 175.50 mg/tab of microcrystalline cellulose, crospovidone, 19.50 mg/tab magnesium stearate, 15.60 mg/tab citric acid, and 10.40 mg/tab sucralose (pages 24-26 [0057]-[0059], examples 1, 3 and 4).
Thus, the cited claims of the instant application are anticipated since Moe et al. specifically teaches administration of an acetaminophen dosage form comprising one or more compounds that reduce liver damage caused by acetaminophen including microcrystalline cellulose, mannitol and sucralose. Moreover, Moe et al. specifically teaches amounts effective in reducing liver damage caused by APAP including 10.40 mg/tab sucralose.
Therefore, the method of Moe et al. which comprises administering a compound to a subject in need thereof wherein the compound is sucralose in an amount effective in reducing liver damage caused by APAP will inherently reduce liver damage caused by acetaminophen (APAP) wherein the liver damage includes necrosis or vacuolization of the liver. Claims 10 and 20 are anticipated since Moe et al. specifically teaches the administration of sucralose in an amount effective in reducing liver damage caused by APAP as disclosed in the instant application and thus administration of the dosage form of Moe et al. will inherently reduce the formation of NAPQI from acetaminophen as claimed in claims 10 and 20.
With respect to the limitation that the mannitol, sucralose, and any combination thereof are active ingredients, said limitation is anticipated since Moe teaches adding sucralose in the same amount as disclosed which reduces liver damage and thus said compound is inherently an active ingredient.
Thus, the cited claims of the instant application are rejected in view of the prior art teachings.
Claims 1-3, 5, 8, 10-13, 15, 18 and 20-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Elphick et al. WO 2008/007150 A1.
Claims 1-3, 5, 8, 10-13, 15, 18 and 20-23 of the instant application claim a method for reducing liver damage caused by acetaminophen (APAP) comprising administering a compound to a subject in need thereof wherein the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof as an active ingredient, in an amount effective in reducing liver damage caused by APAP as well as a method for administering acetaminophen to a subject in need thereof comprising administering to the subject acetaminophen and a compound as an active ingredient in an amount effective in in reducing liver damage caused by APAP, wherein the compound selected from the group consisting of mannitol, sucralose, and any combination thereof.
As defined on pages 5-6 of the instant specification an amount effective in reducing liver damage caused by APAP is interpreted as the amount of mannitol is 10-250 mg, the amount of sucralose is 10-250 mg, and combinations thereof.
Elphick et al. teaches pharmaceutical composition comprising paracetamol and methods of producing these compositions (abstract). Elphick et al. teaches preparing paracetamol composition with preferred carrier materials selected from the group consisting of water-soluble organic and inorganic materials, surfactants, polymers and mixtures thereof (page 5 lines 15-16). Elphick et al. teaches a range of formulations containing paracetamol as an illustrative example of an active agent were produced based on different excipients, different active loadings, and different process conditions (page 19 lines 10-18). The excipients were chosen from hydroxypropyl cellulose (Klucel EF, Herlus), polyvinyl pyrrolidone (PVP k30, Aldrich), hydroxypropyl methyl cellulose (HPMC, Mw 10k, 5cps, Aldrich), polyethylene glycol (PEG, Mw 6,000, Fluka), Tween 80 (Aldrich), pluronic F68 (BASF), pluronic F127 (Aldrich), span 80 (Aldrich), cremphor RH40 (BASF), mannitol (Aldrich), and sodium alginate (Aldrich) (page 19 lines 20-24).
Elphick et al. specifically exemplifies Example 11 comprising 200 mg paracetamol, 400 mg hydroxypropyl cellulose, 100 mg Pluronic® F127, 100 mg polysorbate 80 (Tween® 80), and 200 mg mannitol (page 23 lines 27-31). Example 12 of Elphick et al. comprises 200 mg Paracetamol, 500 mg hydroxypropyl cellulose, 100 mg Pluronic® F127, and 200 mg Mannitol (page 24 lines 12-26). Example 13 of Elphick et al. comprises 200 mg Paracetamol, 600 mg hydroxypropyl cellulose, 50 mg Pluronic® F127, 50 mg polysorbate 80 (Tween® 80), and 100 mg Mannitol (page 24 line 28-page 25 line 5).
Elphick et al. further teaches that these compounds are administered for the treatment of pain (claim 19 page 34).
Thus, the cited claims of the instant application are anticipated since Elphick et al. specifically teaches an acetaminophen dosage for administration for the treatment of pain comprising one or more compounds that reduce liver damage caused by acetaminophen including hydroxypropyl cellulose and mannitol and further comprising a polyoxyethylene-polyoxypropylene block copolymer (Pluronic® F127). Moreover, Elphick et al. specifically teaches amounts effective in reducing liver damage caused by APAP including 100 and 200 mg mannitol.
Therefore, administration of a disclosed formulation of Elphick et al. which comprises mannitol in an amount effective in reducing liver damage caused by APAP will inherently reduce liver damage caused by acetaminophen (APAP) wherein the liver damage includes necrosis or vacuolization of the liver. Claims 10 and 20 are anticipated since Elphick et al. specifically teaches the administration of mannitol in an amount effective in reducing liver damage caused by APAP as disclosed in the instant application and thus administration of the dosage form of Elphick et al. will inherently reduce the formation of NAPQI from acetaminophen as claimed in claims 10 and 20.
With respect to the limitation that the mannitol, sucralose, and any combination thereof are active ingredients, said limitation is anticipated since Elphick teaches adding mannitol in the same amount as disclosed which reduces liver damage and thus said compound is inherently an active ingredient.
Thus, the cited claims of the instant application are rejected in view of the prior art teachings.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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 1-22 are rejected under 35 U.S.C. 103 as being unpatentable over Moe et al. WO 2007/050631 A2 (Provided on IDS) in view of Lee et al. (1996, JBC, Vol. 271, No. 20, pages 12063-12067) (Provided on IDS) and Hu et al. WO 2012/142724 A1 (U.S. Publication No. 2014/0038921 A1 as English translation) (Provided on IDS).
Claims 1-22 of the instant application claim a method for reducing liver damage caused by acetaminophen (APAP) comprising administering a compound to a subject in need thereof wherein the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof, as an active ingredient, in an amount effective in reducing liver damage caused by APAP as well as a method for administering acetaminophen to a subject in need thereof comprising administering to the subject acetaminophen and a compound as an active ingredient, in an amount effective in reducing liver damage caused by APAP, wherein the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof.
As defined on pages 5-6 of the instant specification an amount effective in reducing liver damage caused by APAP is interpreted as the amount of microcrystalline cellulose is 100-1000 mg, the amount of mannitol is 10-250 mg, the amount of sucralose is 10-250 mg, the amount of Eudragit® S100 is 0.17-5.5 g, the amount of Pluronic® F68 is 1.4-5.5 g, the amount of menthol is 8-34 mg.
Please note that “In determining whether the invention as a whole would have been obvious under 35 U.S.C. 103, we must first delineate the invention as a whole. In delineating the invention as a whole, we look not only to the subject matter which is literally recited in the claim in question... but also to those properties of the subject matter which are inherent in the subject matter and are disclosed in the specification. . . Just as we look to a chemical and its properties when we examine the obviousness of a composition of matter claim, it is this invention as a whole, and not some part of it, which must be obvious under 35 U.S.C. 103.” In re Antonie, 559 F.2d 618, 620, 195 USPQ 6,8 (CCPA 1977). See also Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993) (The Board rejected a claim directed to a method for protecting a plant from plant pathogenic nematodes by inoculating the plant with a nematode inhibiting strain of P. cepacia. A U.S. patent to Dart disclosed inoculation using P. cepacia type Wisconsin 526 bacteria for protecting the plant from fungal disease. Dart was silent as to nematode inhibition but the Board concluded that nematode inhibition was an inherent property of the bacteria. The Board noted that applicant had stated in the specification that Wisconsin 526 possesses an 18% nematode inhibition rating.).
Moe et al. teaches orally dissolvable/disintegrable dosage forms adapted for direct oral dosing (abstract). Moe et al. teaches an orally dissolved/disintegrable tablet adapted for direct oral dosing comprising acetaminophen [0014]. Moe et al. teaches that the dosage form, caplet or tablet may be stored in bulk, for example drums, bulk bins, hoppers, and/or packed in conventional openable and reclosable multi-tablet bottles, or other similar packaging [0015]. Moe et al. teaches that disintegration means that the dosage form falls apart into smaller particles and/or aggregates and portions will begin to dissolve when the dosage form is placed in the mouth and preferably on the tongue [0018].
Moe et al. specifically teaches a formulation for tableting by direct compression comprising paracetamol (acetaminophen, APAP), 325.42 mg/tab of mannitol, 175.50 mg/tab of microcrystalline cellulose, crospovidone, 19.50 mg/tab magnesium stearate, 15.60 mg/tab citric acid, and 10.40 mg/tab sucralose (pages 24-26 [0057]-[0059], examples 1, 3 and 4).
Thus, Moe et al. specifically teaches administration of an acetaminophen dosage form comprising one or more compounds that reduce liver damage caused by acetaminophen including microcrystalline cellulose, mannitol and sucralose. Moreover, Moe et al. specifically teaches amounts effective in reducing liver damage caused by APAP including 175.50 mg/tab of microcrystalline cellulose and 10.40 mg/tab sucralose. Moe et al. further teaches that the composition comprising acetaminophen contains the combination of mannitol and sucralose as claimed in claims 4, 6, 14 and 16 of the instant application.
Moe et al. does not specifically teach that the dosage form disclosed therein will reduce liver damage caused by APAP. Moe et al. does not specifically teach an amount of mannitol as disclosed by Applicant that reduces liver damage. Moe et al. does not teach mannitol and sucralose in a 1:1 weight ratio.
However, the method of Moe et al. which comprises administering a dosage from comprising acetaminophen in combination with a compound wherein the compound is sucralose, in an amount effective in reducing liver damage caused by APAP will necessarily reduce liver damage caused by acetaminophen (APAP).
In addition, Lee et al. teaches that CYP2E1 mediates hepatotoxicity of acetaminophen and that inhibition of CYP2E1 protects against liver toxicity induced by high dosages of acetaminophen (see abstract, pages 12066-12067 and Figure 5).
Hu et al. specifically demonstrates that sucralose, mannitol, and microcrystalline cellulose are excipients used in pharmaceutical formulations that inhibit CYP2E1 (Table 7 page 12).
Accordingly, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art that the formulation of Moe et al. which comprises acetaminophen in combination with sucralose, mannitol and microcrystalline cellulose would reduce liver damage caused by APAP since Lee et al. teaches that CYP2E1 mediates hepatotoxicity of acetaminophen and that inhibition of CYP2E1 protects against liver toxicity induced by high dosages of acetaminophen and Hu et al. teaches that sucralose, mannitol and microcrystalline cellulose are inhibitors of CYP2E1. Thus, it would have been obvious to a person of ordinary skill in the art to administer the formulation of Moe et al. for the purpose of reducing liver damage caused by APAP since said formulation includes components known in the art for inhibiting CYP2E1 which is known to promote liver damage induced by acetaminophen. In addition, Moe et al. further teaches that the acetaminophen formulation contains other components identified in Hu et al. as CYP2E1 inhibitors including crospovidone, citric acid, and magnesium stearate which further supports the reduction of liver damage caused by APAP.
Claims 2, 10, 12 and 20 are also rendered obvious since Moe et al. specifically teaches including the compounds as claimed in the formulation in amounts that reduce liver damage and thus reducing necrosis or vacuolization of the liver and the formation of NAPQI from acetaminophen as claimed in claims 2, 10, 12 and 20 is also rendered obvious.
With respect to the amount of mannitol to reduce liver damage, Moe et al. teaches 325.42 mg/tab of mannitol and Hu et al. teaches that the minimum dosage of mannitol for inhibiting CYP2E1 is 10 mg (Table 7 page 12). Therefore, since the tablets of Moe et al. contain more than 10 mg/tab of mannitol, it would have been obvious to a person of ordinary skill in the art that the mannitol in the tablet of Moe et al. would inhibit CYP2E1 and thus reduce liver damage caused by acetaminophen. Thus claims 8 and 18 of the instant application are rendered obvious in view of the cited prior art teachings.
With respect to claims 7, 17, 21 and 22 generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").
Claims 3 and 13 are rendered obvious since Moe teaches the dosage form comprises natural and artificial mint flavor and thus the use of menthol is rendered obvious (page 24). In addition, Moe teaches that the dosage form may also contain a coating material such as Eudragit® which is poly(methacrylic acid-methyl methacrylate) (page 15 [0032]).
With respect to the limitation that the mannitol, sucralose, and any combination thereof are active ingredients, said limitation is rendered obvious since Moe teaches adding sucralose in the same amount as disclosed which reduces liver damage and thus said compound is necessarily an active ingredient. Furthermore, Moe teaches including the same excipients as claimed and thus said compounds are necessarily capable of being active ingredients as claimed and thus referring to the same compounds as active ingredients does not patentably distinguish the instant claims over the prior art.
Thus, the cited claims of the instant application are rejected.
Claims 1-3, 5, 8, 10-13, 15, 18 and 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Elphick et al. WO 2008/007150 A1 in view of Lee et al. (1996, JBC, Vol. 271, No. 20, pages 12063-12067) (Provided on IDS) and Hu et al. WO 2012/142724 A1 (U.S. Publication No. 2014/0038921 A1 as English translation) (Provided on IDS).
Claims 1-3, 5, 8, 10-13, 15, 18 and 20-23 of the instant application claim a method for reducing liver damage caused by acetaminophen (APAP) comprising administering a compound to a subject in need thereof wherein the compound is selected from the group consisting of mannitol, sucralose, and any combination thereof as an active ingredient, in an amount effective in reducing liver damage caused by APAP as well as a method for administering acetaminophen to a subject in need thereof comprising administering to the subject acetaminophen and a compound as an active ingredient in an amount effective in in reducing liver damage caused by APAP, wherein the compound selected from the group consisting of mannitol, sucralose, and any combination thereof.
As defined on pages 5-6 of the instant specification an amount effective in reducing liver damage caused by APAP is interpreted as the amount of mannitol is 10-250 mg, the amount of sucralose is 10-250 mg, and combinations thereof.
Elphick et al. teaches pharmaceutical composition comprising paracetamol and methods of producing these compositions (abstract). Elphick et al. teaches preparing paracetamol composition with preferred carrier materials selected from the group consisting of water-soluble organic and inorganic materials, surfactants, polymers and mixtures thereof (page 5 lines 15-16). Elphick et al. teaches a range of formulations containing paracetamol as an illustrative example of an active agent were produced based on different excipients, different active loadings, and different process conditions (page 19 lines 10-18). The excipients were chosen from hydroxypropyl cellulose (Klucel EF, Herlus), polyvinyl pyrrolidone (PVP k30, Aldrich), hydroxypropyl methyl cellulose (HPMC, Mw 10k, 5cps, Aldrich), polyethylene glycol (PEG, Mw 6,000, Fluka), Tween 80 (Aldrich), pluronic F68 (BASF), pluronic F127 (Aldrich), span 80 (Aldrich), cremphor RH40 (BASF), mannitol (Aldrich), and sodium alginate (Aldrich) (page 19 lines 20-24).
Elphick et al. specifically exemplifies Example 11 comprising 200 mg paracetamol, 400 mg hydroxypropyl cellulose, 100 mg Pluronic® F127, 100 mg polysorbate 80 (Tween® 80), and 200 mg mannitol (page 23 lines 27-31). Example 12 of Elphick et al. comprises 200 mg Paracetamol, 500 mg hydroxypropyl cellulose, 100 mg Pluronic® F127, and 200 mg Mannitol (page 24 lines 12-26). Example 13 of Elphick et al. comprises 200 mg Paracetamol, 600 mg hydroxypropyl cellulose, 50 mg Pluronic® F127, 50 mg polysorbate 80 (Tween® 80), and 100 mg Mannitol (page 24 line 28-page 25 line 5).
Elphick et al. further teaches that these compounds are administered for the treatment of pain (claim 19 page 34).
Thus, Elphick et al. specifically teaches an acetaminophen dosage for administration for the treatment of pain comprising one or more compounds that reduce liver damage caused by acetaminophen including hydroxypropyl cellulose and mannitol and further comprising a polyoxyethylene-polyoxypropylene block copolymer (Pluronic® F127). Moreover, Elphick et al. specifically teaches amounts effective in reducing liver damage caused by APAP including 100 and 200 mg mannitol.
Elphick et al. does not specifically teach that the dosage form disclosed therein will reduce liver damage caused by APAP.
However, the method of Elphick et al. which comprises administering a dosage from comprising acetaminophen in combination with a compound wherein the compound is mannitol, in an amount effective in reducing liver damage caused by APAP will necessarily reduce liver damage caused by acetaminophen (APAP).
In addition, Lee et al. teaches that CYP2E1 mediates hepatotoxicity of acetaminophen and that inhibition of CYP2E1 protects against liver toxicity induced by high dosages of acetaminophen (see abstract, pages 12066-12067 and Figure 5).
Hu et al. specifically demonstrates that the compounds included in the composition of Elphick et al. including mannitol, hydroxypropyl cellulose, polyoxyethylene-polyoxypropylene block copolymer (Pluronic®), Tween® 80 are excipients used in pharmaceutical formulations that inhibit CYP2E1 (Table 7 page 12).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art that the formulation of Elphick et al. which comprises acetaminophen in combination with components specifically taught by Hu et al. that inhibit CYP2E1 would reduce liver damage caused by APAP since Lee et al. teaches that CYP2E1 mediates hepatotoxicity of acetaminophen and that inhibition of CYP2E1 protects against liver toxicity induced by high dosages of acetaminophen and Hu et al. specifically teaches that hydroxypropyl cellulose, Pluronic® (polyoxyethylene-polyoxypropylene block copolymer), polysorbate 80 (Tween® 80), and Mannitol are all inhibitors of CYP2E1. Thus, it would have been obvious to a person of ordinary skill in the art to administer the formulation of Elphick et al. for the purpose of reducing liver damage caused by APAP since said formulation includes components known in the art for inhibiting CYP2E1 which is known to promote liver damage induced by acetaminophen. Thus since the formulation of Elphick et al. contains a combination of CYP2E1 inhibitors, a person of ordinary skill in the art would have reasonably expected that administration of said formulation of acetaminophen of Elphick et al. would reduce liver damage caused by APAP.
Claims 2, 10, 12 and 20 are also rendered obvious since Elphick et al. specifically teaches including the compounds as claimed in the formulation in amounts that reduce liver damage and thus reducing necrosis or vacuolization of the liver and the formation of NAPQI from acetaminophen as claimed in claims 2, 10, 12 and 20 is also rendered obvious.
With respect to the amount of mannitol to reduce liver damage, Elphick et al. teaches 100 mg or 200 mg of mannitol and Hu et al. teaches that the minimum dosage of mannitol for inhibiting CYP2E1 is 10 mg (Table 7 page 12). Therefore, since the compositions of Elphick et al. contain more than 10 mg of mannitol, it would have been obvious to a person of ordinary skill in the art that the mannitol in the composition of Elphick et al. would inhibit CYP2E1 and thus reduce liver damage caused by acetaminophen. Thus claims 8, 18, 21 and 22 of the instant application are rendered obvious in view of the cited prior art teachings.
Claims 3, 13 and 23 are rendered obvious since Elphick et al. specifically teaches that the formulation contains Pluronic® (polyoxyethylene-polyoxypropylene block copolymer).
With respect to the limitation that the mannitol, sucralose, and any combination thereof are active ingredients, said limitation is rendered obvious since Elphick et al. teaches adding mannitol in the same amount as disclosed which reduces liver damage and thus said compound is necessarily an active ingredient. Furthermore, Elphick et al. teaches including the same excipients as claimed and thus said compounds are necessarily capable of being active ingredients as claimed and thus referring to the same compounds as active ingredients does not patentably distinguish the instant claims over the prior art.
Thus, the cited claims of the instant application are rejected.
Conclusion
Claims 1-23 are rejected. 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 KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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