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 the Claims
Claims 48-67 filed on 10/25/2022 are currently pending.
Election/Restrictions
Applicant's election with traverse of Group II, claims 64-67 in the reply filed on 09/04/2025 is acknowledged. The traversal is on the ground(s) that Group I recites steps B and C in addition to step A in view of claims 59 and 62. This is not found persuasive because the technical feature between Groups I and II is based on the independent claims 48 and 64 and not on dependent claims 59 and 62 as Applicant argues. As such, the technical feature that is recited in both independent claims 48 and 64 remains being step A.
The requirement is still deemed proper and is therefore made FINAL.
Specification
The disclosure is objected to because of the following informalities: The schemes on page 13 use the term “ou” that is unclear and fails to conform with current U.S. practice.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 64-67 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.
Claim 64 is rendered vague and indefinite for the following reasons:
The term “ou” in the scheme is unclear and fails to conform with current U.S. practice.
The limitation “R and X being defined above” is unclear as the definition for the variables/substituents has not been set forth in the claim. For purpose of applying art, R and X are interpreted in view of the specification, i.e. R represents a hydrogen atom, a protective group selected from a benzyl or acetate, and X represents a nitro group or a nitroso group.
The limitation “a step B of hydrogenation of the compound of Formula 2, to obtain: 4-Aminophenol, where R is a benzyl group or a hydrogen atom, or paracetamol, where R is an acetate group” is indefinite because:
A skilled artisan would understand and expect that the hydrogenation step B of formula 2 would reduce the nitro/nitroso group to amine group. However, the claim produces paracetamol with acyl group substituting the amine group. It is unclear how the hydrogenation step B can produce the acylated product, paracetamol, thus rendering the claim indefinite as being incomplete for omitting essential steps/elements, such omission amounting to a gap between the steps. See MPEP § 2172.01.
The scope of “4-Aminophenol, where R is a benzyl group or a hydrogen atom” is unclear as 4-Aminophenol can only have R as a hydrogen atom but cannot have R as a benzyl group.
The scope of “paracetamol, where R is an acetate group” is also unclear as paracetamol can only have R as a hydrogen atom.
The products of step B that are presented in the scheme are not consistent with the limitation “a step B of hydrogenation of the compound of Formula 2, to obtain: 4-Aminophenol, where R is a benzyl group or a hydrogen atom, or paracetamol, where R is an acetate group”. In other words, the scheme does not present R groups in the products that are obtained by the hydrogenation step B.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 64 recites the broad recitation before “preferably” or “in particular”, and the claim also recites the narrower statement of the range/limitation after “preferably” or “in particular”. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The limitation “a step C of acylation of 4-aminophenol, to obtain paracetamol” renders the scope of the claim indefinite. In view of the scheme, step B produces either
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(paracetamol) or
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, in which only the latter is acetylated to
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by step C. Thus, it is unclear whether step C - that produces paracetamol - is an optional step, especially when step B produces
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instead of
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. In other words, step C would not be conducted if step B produces
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. For purpose of applying art, step C of claims 64 and 67 will be interpreted as being an optional step.
Claims 65-67 are also rendered indefinite for their dependency on claim 64.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 67 recites the broad recitation before “in particular”, and the claim also recites the narrower statement of the range/limitation after “in particular”. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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 (i.e., changing from AIA to pre-AIA ) 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 64 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Patent number US5,414,148 (US’148) in view of Patent number RU2574733C1 (RU’733). As set forth above, step C of claims 64 and 67 are interpreted herein as being an optional step when step B produces paracetamol.
Regarding claim 64-step A, US’148 teaches nitrosation of phenol with sodium nitrite to obtain p-nitrosophenol. The reference teaches a batch process but fails to teach that the reaction step is continuous. However, in view of MPEP § 2144.04, making the process continuous is one the various common practices which the court has held normally require only ordinary skill in the art and hence are considered routine expedients. As such, the claimed continuous operation would have been obvious in light of the batch process of US’148.
Regarding claim 64-step B, US’148 fails to teach or suggest hydrogenation of the compound of Formula 2 to obtain paracetamol. The deficiency is cured by RU’733.
RU’733 teaches a process of obtaining paracetamol by stirring p-nitrosophenol with Ni-Re and acetic anhydride under a hydrogen pressure of 2.0-4.0 atm hydrogen at a temperature of 60-70 ° C for 0.5-2.0 hours.
Paracetamol is known for its analgesic effect and used to treat mild to moderate pain and reduce fever. Accordingly, a skilled artisan would have been motivated to use the methods of RU’733 in US’148 with a reasonable expectation of success in converting p-nitrosophenol of US’148 to paracetamol.
Regarding claim 67, RU’733 teaches that paracetamol is purified by distillation (Example 5).
It would thus have been prima facie obvious to a skilled artisan before the effective filing date of the instant invention to prepare paracetamol by step A of nitrosation of a compound of formula 1 followed by step B of hydrogenating formula 1 to obtain paracetamol in view of the combination of US’148 and RU’733
Claims 64 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Ergan (Ergan, B. T. et al. “Regioselective nitration of phenol under continuous microwave irradiation” Journal of Microwave Power and Electromagnetic Energy Volume 51, 2017 - Issue 4; cited in PTO-892 07/07/2025) in view of Zheng (Zheng, Y. et al. “A Green Reduction of Aromatic Nitro Compounds to Aromatic Amines Over a Novel Ni/SiO2 Catalyst Passivated with a Gas Mixture” Catal Lett (2008) 124:268–276) and Patent number US6,215,024 (US’024).
Regarding claim 64-step A, Ergan teaches nitration of phenol under continuous microwave irradiation to obtain p-nitrophenol.
Ergan fails to teach step B of hydrogenating p-nitrophenol to obtain p-aminophenol and step C of acylating p-aminophenol to obtain paracetamol.
The deficiencies are cured by Zheng and US’024.
Regarding claim 64-step B, Zheng teaches hydrogenation of p-nitrophenol to obtain p-aminophenol (Table 1, Entry 3).
Regarding claim 64-step C, US’024 teaches acylating of p-aminophenol to obtain p-hydroxy acetanilide (paracetamol) (Examples 10-11).
Regarding claim 67, US’024 further teaches after completion of the reaction, the reaction mixture was filtered and the filtrate was concentrated on rotavapor/distilled to get the pure product
Zheng teaches that aromatic nitro compounds are important intermediates for
agrochemicals, pharmaceuticals, dyestuffs, urethanes and other industrially important products and US’024 teaches that paracetamol is known for its medicinal use as a non-prescription analgesic and anti-pyretic agent with properties similar to aspirin. Accordingly, a skilled artisan would have been motivated to use the methods of Ergan in obtaining p-nitrophenol and combine the methods with the methods of Zheng and US’024 with a reasonable expectation of success in obtaining paracetamol.
It would thus have been prima facie obvious to a skilled artisan before the effective filing date of the instant invention to prepare paracetamol by step A of nitrating a compound of formula 1 to obtain p-nitrophenol, step B of hydrogenating p-nitrophenol to obtain p-aminophenol and step C of acylating p-aminophenol to obtain paracetamol in view of the combination of Ergan, Zheng and US’024.
Claim 65 is rejected under 35 U.S.C. 103 as being unpatentable over Ergan (Ergan, B. T. et al. “Regioselective nitration of phenol under continuous microwave irradiation” Journal of Microwave Power and Electromagnetic Energy Volume 51, 2017 - Issue 4; cited in PTO-892 07/07/2025) in view of Zheng (Zheng, Y. et al. “A Green Reduction of Aromatic Nitro Compounds to Aromatic Amines Over a Novel Ni/SiO2 Catalyst Passivated with a Gas Mixture” Catal Lett (2008) 124:268–276) and Patent number US6,215,024 (US’024) as applied to claims 64 and 67 above, and further in view of Patent number GB602278A (GB’278).
The teachings of Ergan, Zheng and US’024 have been set forth above.
Regarding claim 65, the references fail to teach or suggest wherein step B of hydrogenation is being carried out continuously in three reactors in series. The deficiency is however cured by GB’278.
GB’278 teaches improvements relating to temperature control of exothermic hydrogenation reactions, specifically hydrogenation of nitro aromatics to aromatic amines by carrying out a continuous hydrogenation reaction in multiple reaction zones connected in series (see Figure). The reference teaches that the purpose is to improve the quantity and quality of the product at a high level. Hence, a skilled artisan would have been motivated to use the methods of GB’278 in the hydrogenation process of Zheng with a reasonable expectation of success in controlling the exothermic reaction and in improving the quantity and quality of the p-aminophenol product.
It would thus have been prima facie obvious to a skilled artisan before the effective filing date of the instant invention to prepare paracetamol by step A of nitrating a compound of formula 1 to obtain p-nitrophenol, step B of hydrogenating p-nitrophenol to obtain p-aminophenol, wherein step B of hydrogenation being carried out continuously in three reactors in series and step C of acylating p-aminophenol to obtain paracetamol in view of the combination of Ergan, Zheng, US’024 and GB’278.
Claims 64 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Patent number US5,414,148 (US’148) in view of Patent number CN112279781A (CN’781) and Patent number US6,215,024 (US’024).
Regarding claim 64-step A, US’148 teaches nitrosation of phenol with sodium nitrite to obtain p-nitrosophenol. The reference teaches a batch process but fails to teach that the reaction step is continuous. However, in view of MPEP § 2144.04, making the process continuous is one the various common practices which the court has held normally require only ordinary skill in the art and hence are considered routine expedients. As such, the claimed continuous operation would have been obvious in light of the batch process of US’148.
US’148 fails to teach step B of hydrogenating p-nitrosophenol to obtain p-aminophenol and step C of acylating p-aminophenol to obtain paracetamol.
The deficiencies are cured by CN’781 and US’024.
Regarding claim 64-step B, CN’781 teaches hydrogenation of p-nitrosophenol to obtain p-hydroxyaniline (p-aminophenol) ([0079]-[0081]).
Regarding claim 64-step C, US’024 teaches acylating of p-aminophenol to obtain p-hydroxy acetanilide (paracetamol) (Examples 10-11).
Regarding claim 67, US’024 further teaches after completion of the reaction, the reaction mixture was filtered and the filtrate was concentrated on rotavapor/distilled to get the pure product
US’024 teaches that paracetamol is known for its medicinal use as a non-prescription analgesic and anti-pyretic agent with properties similar to aspirin. Accordingly, a skilled artisan would have been motivated to use the methods of US’148 in obtaining p-nitrophenol and combine the methods with the methods of CN’781 and US’024 with a reasonable expectation of success in obtaining paracetamol.
It would thus have been prima facie obvious to a skilled artisan before the effective filing date of the instant invention to prepare paracetamol by step A of nitrating a compound of formula 1 to obtain p-nitrophenol, step B of hydrogenating p-nitrophenol to obtain p-aminophenol and step C of acylating p-aminophenol to obtain paracetamol in view of the combination of US’148, CN’78 and US’024.
Claim 66 is rejected under 35 U.S.C. 103 as being unpatentable over US’148 (US’148, B. T. et al. “Regioselective nitration of phenol under continuous microwave irradiation” Journal of Microwave Power and Electromagnetic Energy Volume 51, 2017 - Issue 4; cited in PTO-892 07/07/2025) in view of Patent number US5,414,148 (US’148) in view of Patent number CN112279781A (CN’781) and Patent number US6,215,024 (US’024) as applied to claims 64 and 67 above, and further in view of Patent number GB602278A (GB’278).
The teachings of US’148, CN’781 and US’024 have been set forth above.
Regarding claim 65, the references fail to teach or suggest wherein step B of hydrogenation is being carried out continuously in three reactors in series. The deficiency is however cured by GB’278.
GB’278 teaches improvements relating to temperature control of exothermic hydrogenation reactions, specifically hydrogenation of nitro aromatics to aromatic amines by carrying out a continuous hydrogenation reaction in multiple reaction zones connected in series (see Figure). The reference teaches that the purpose is to improve the quantity and quality of the product at a high level. Hence, a skilled artisan would have been motivated to use the methods of GB’278 in the hydrogenation process of CN’781 with a reasonable expectation of success in controlling the exothermic reaction and in improving the quantity and quality of the p-aminophenol product.
It would thus have been prima facie obvious to a skilled artisan before the effective filing date of the instant invention to prepare paracetamol by step A of nitrating a compound of formula 1 to obtain p-nitrophenol, step B of hydrogenating p-nitrosophenol to obtain p-aminophenol, wherein step B of hydrogenation being carried out continuously in three reactors in series and step C of acylating p-aminophenol to obtain paracetamol in view of the combination of US’148, CN’781, US’024 and GB’278.
Conclusion
Claims 64-67 are rejected and no claims are allowed.
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/MEDHANIT W BAHTA/Primary Examiner, Art Unit 1692