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 .
DETAILED ACTION
Claims 1-24 of E. DAVIOUD-CHARVET, et al, US 18/579,048 (01/12/2024) are pending and are under examination on merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claim 16 is objected to because of the following informalities: the claim should be ended with a period. Appropriate correction is required.
Rejections 35 U.S.C. 112(b)
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.
Claim 17 is rejected under 35 U.S.C. 112(b) as being indefinite because the term of “trifluoroacetic anhydride/triflic acid” is not clear. One ordinary skill in the art does not know the claimed “trifluoroacetic anhydride/triflic acid” is “trifluoroacetic anhydride and triflic acid” or is ““trifluoroacetic anhydride or triflic acid” or both.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 7 is rejected under 35 U.S.C. 112(d) 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends
Claim 7 dependents on claim 1. Claim 1 recites a step of bromination of the compound formula (III), therefore, one ordinary skill in the art would be appraised that the bromination in claim 1 is carried out with an addition of a brominating agent. Therefore, claim 7 cannot further limit the subject matter of claim 1, and 112(d) rejection is proper. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
§ 102 Rejection over Bergeron
Claim 10 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by F. Bergeron, et al. Nucleic acids research 32.21, 6154-6163 (2004) (“Bergeron”).
Bergeron teaches compound of 6-bromomethyl-2-methyl-1,4-naphthoquinone having a structure as indicated below. Bergeron at page 6155, right col. 6-bromomethyl-2-methyl-1,4-naphthoquinone.
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The Bergeron compound maps formula I in claim 10 as R is bromomethyl that is a haloC1alkyl , therefore, claim 10 is anticipated.
§ 102 Rejection over Heller
Claims 11, 16 and 20 are rejected under 35 U.S.C. 102(a)(1)as being anticipated by H.G. Heller, US4931221 (1990) (“Heller”).
Heller teaches the 7-methoxy- 3-methyl-1-naphthol which has a chemical structure as indicated below. Heller at col. 20, Example 5, line 2-3.
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The Heller compound has the same chemical structure as that of the claimed species compound 23 in claim 16, which maps the formula (V) of claims 11 and 20 as R is OMe, therefore, claims 11, 16 and 20 are anticipated.
§ 102 Rejection over CA Abstract
Claims 13, 16 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CA abstract RN # 2168087-86-1.
The CA abstract indicates that compound RN# 2168087-86-1 has been disclosed by FCH group at least since 01/02/2018. See attached CA abstract.
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The compound RN# 2168087-86-1 is the claimed species compound 10 in claim 16, which maps the formula (III) in claim 13 and 22 as R is CF3, therefore, claims 13, 16 and 22 are anticipated.
Claims 14, 16 and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CA abstract RN # 541677-62-6.
The CA abstract indicates that compound RN# 1541677-62-6 has been disclosed by Aurora Fine Chemicals at least since 02/11/2014. See attached CA abstract.
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The compound RN# 1541677-62-6 is the claimed species compound 9 in claim 16, which maps the formula (II) in claim 14 and 23 as R is CF3, therefore, claims 14, 16 and 23 are anticipated.
§ 102 Rejection over Hudkins
Claim 15 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by R. L. Hudkins, et al, Bioorganic & medicinal chemistry letters 21.18, 5493-5497 (2011) (“Hudkins”) that has been recited in the IDS filed by the applicant on 01/12/2024.
Hudkins teaches the following reaction:
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Hudkins at page 5494, Scheme 3, step b(i).
While Hudkins does not specific the product of the above reaction, however, one ordinary skill in the art would be appraised that product has a chemical structure as indicated below because Hudkins teaches that the reaction is an Aldo adduction reaction. Hudkins at page 5494, right col. paragraph 2, line 1-4.
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The Hudkins product maps the formula (VII) in claim 15 as R is OCH2CH2CH2Cl, therefore, claim 15 is anticipated.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
35 USC § 103 Rejection over a Combination of Rodo, Heller, Bringmann, Hulme, Heim and Kraus
Claims 1-3, 5-8,12 and 21 are rejected under 35 USC § 103 Rejection over a combination of E.C. Rodo, et al, Eur. J. Org. Chem. 1982–1993 (2016) (“Rodo”); H.G. Heller, US4931221 (1990) (“Heller”); A. N. Hulme, et al. J. Org. Chem. 60, 1265-1270(1995)(“Hulme”); R. Heim, et al. Journal of medicinal chemistry 51.16, 5064-5074 (2008)(“Heim”) and A. Kraus, Doctoral dissertation, (2008)(“Kraus”).
E.C. Rodo, et al, Eur. J. Org. Chem. 1982–1993 (2016) (“Rodo”) cited by Applicant in the IDS form filed on 01/12/2024
Rodo teaches that 1,4-Naphthoquinones been used for centuries in folk medicine, cosmetics, and industrial dye applications. Rodo at page 1982, left col. line 3-5. Rodo teaches that recent discovery of the antimalarial lead 3- [4- (trifluoro methyl) benzyl] menadione, has led to reassessment of the synthetic methodologies used to prepare large numbers of diverse analogues and potential metabolites functionalized on both the eastern and western parts of the molecule. Rodo at page 1983, left col. paragraph 3, line 1-6.
Rodo teaches a method for synthesis of 2-methylnaphthols from tetralones and oxidation of the 2-methylnaphthols into corresponding 1,4-naphthoquinones. Rodo at Scheme 3 at page 1984, Scheme 5 at page 1985 and Table 1 at page 1985. Per Table 1, Rodo teaches that 6-methoxy-2-methylnapthol 4a can be oxidated into the (6-MeO)-VitK3 with a yield of 99%. Rodo at Table 1 at page 1985.
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Per Scheme 8, Rodo teaches that 6-MeO-VitK3 analogs can be used a building block to synthesize (3-benzyl)-VitK3 analogs. Rodo at page 1986, Scheme 8.
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Per Table 3, Rodo further teaches that (3-benzyl)-VitK3 analogs made from (6-MeO)-VitK3 such as 17a, 18a and 20m all have good antimalarial activities in vitro. Rodo at page 1986, Table 3. Therefore, one ordinary skill in the art seeking antimalarial agents is motivated to synthesize (6-MeO)-VitK3 as a building block for analogs preparation.
The (6-MeO)-VitK3 in the Rodo method:
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maps the formula (I) in claim 1 as R is OMe.
The Rodo method differs from the fourth step recited by instant claim 1 in that compound 4a is not the compound of formula (V), rather it is a position isomers of one species of the claimed formula (V).
H.G. Heller, US4931221 (1990) (“Heller”)
As mentioned in the 102 rejection above, Heller teaches compound 7-methoxy- 3-methyl-1-naphthol which has a chemical structure as indicated below. Heller at col. 20, Example 5, line 2-3.
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The Heller compound is a position isomer of the Rodo compound 4a, and the Heller compound maps the compound of formula (V) in claim 1 as R is OMe. After comparing the structures of the Heller compound 7-methoxy- 3-methyl-1-naphthol and the Rodo compound 4a, one ordinary skill in art would be appraised that 7-methoxy- 3-methyl-1-naphthol also can be used to prepare (6-MeO)-VitK3 with the Rodo method as indicated below.
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Given the Heller compound 7-methoxy-3-methyl-1-naphthol is a position isomer of the Rodo compound 4a, there is a reasonable expectation that oxidation of 7-methoxy-3-methyl-1-naphthol with the Rodo method would produce (6-MeO)-VitK3 in a similar yield as with the Rodo compound 4a . MPEP2144.09.II.
Difference between the Combination of Rodo-Heller and the Claims
The combination of Rodo and Heller differs from the instant claim 1 in that the combination does not teach to synthesize the Heller compound 7-methoxy- 3-methyl-1-naphthol with the claimed steps.
A. N. Hulme, et al. J. Org. Chem. 60, 1265-1270(1995)(“Hulme”)
Hulme teaches a method for preparing 7-methoxy-1-naphthol (3) through a step of bromination of 7-methoxy-1-tetralone with Br2 to produce 7-methoxy-2-bromo-1-tetralone and then aromatization of 7-methoxy-2-bromo-1-tetralone with LiBr/Li2CO3 as indicated below.
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Hulme at page 1265, scheme 2 and page 1267, Experimental Section for the preparation of 7-methoxy-1-naphthol (3).
The Hulme method differs from the claimed second and third steps only in that 7-methoxy-2-bromo-1-tetralone, 7-methoxy-1-naphthol used by Hulme does not comprise one CH3 group at the C-3 position as claimed in the formula (III) and formula (IV) respectively. However, to synthesize the Heller compound 7-methoxy-3-methyl-1-naphthol, one ordinary skill in the art would use 7-methoxy-3-methyl 1-tetralone as the starting material with the method taught by Hulme as indicated below.
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R. Heim, et al. Journal of medicinal chemistry 51.16, 5064-5074 (2008)(“Heim”).
Heim teaches a method of preparation of 6-methoxy-3-methyl-1-tetralone through intramolecular cyclisation in the presence of AlCl3 as indicated below:
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Heim at page 5067, Scheme 5, preparation of 2e from 2f.
It should be noted that the Heim product 6-methoxy-3-methyl-1-tetralone is a position isomer of the proposed 7-methoxy-3-methyl 1-tetralone, one ordinary skill in the art is motivated to use 3-(4-methoxybenzyl)butanoic acid as the starting material to synthesize the proposed 7-methoxy-3-methyl 1-tetralone with the method taught by Heimn as indicated below.
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A. Kraus, Doctoral dissertation, (2008)(“Kraus”).
Kraus teaches compound 3-(4-Methoxybenzyl)butanoic acid (3.36c). Kraus at page 71 for synthesis of 3.36c that maps the claimed formula (II) as R is OMe.
Obviousness Rationales of the Claims 1-3,5-8, 12 and 21
One ordinary skill in the art would arrive at the claimed invention before the effective filling date of the instant application because one ordinary skill in the art seeking antimalarial agents is motivated to synthesize the (6-MeO)-VitK3 through:
(i). Modification of the Heim method by replacing of the Heim 3-(3-methoxybenzyl)butanoic acid with the Kraus 3-(4-methoxybenzyl)butanoic acid to obtain the proposed 7-methoxy-3-methyl 1-tetralone;
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(ii). Modification of the Hulme method by replacing the Hulme 7-methoxy-1-tetralone with the proposed 7-methoxy-3-methyl 1-tetralone to obtain the Heller compound 7-methoxy- 3-methyl-1-naphthol;
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(iii). Modification the Rodo method by replacing the Rodo 6-methoxy-2-methyl-1-napthol with the Heller compound 7-methoxy- 3-methyl-1-naphthol to obtain (6-MeO)-VitK3 .
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The above proposed method meeting each and every limitation of claims 1-3 and 5, therefore, claims 1-3 and 5 are obvious. It should be noted that the instant claim 5 does not require R in the formulas recited by claim 1 is Br or Cl, therefore, the proposed method also meets the claim 5.
One ordinary skill in the art has a motivation to do so with a reasonable expectation of success for the following reasons:
(i). Rodo teaches that (6-MeO)-VitK3 is a building block for antimalarial agents’ preparation;
(ii). Kraus teaches 3-(4-methoxybenzyl)butanoic acid;
(iii). Heim teaches a method of preparation of tetralone through intramolecular cyclisation as indicated above;
(iv). Hulem teaches a method for preparing naphthol through a step of bromination of tetralone followed by aromatization as indicated above; and
(v). Rodo teaches a method of oxidization of naphthol to (6-MeO)-VitK3.
The rationales are supported by “combining prior art elements according to known methods to yield predictable results” and “simple substitution of one known element for another to obtain predictable results”. MPEP 2143.I. A-B.
Claim 6 is obvious because Heim teaches that the intramolecular cyclisation in the proposed method is conducted in the presence of AlCl3 that is a Lewis acid.
Claim 7 is obvious because Hulme teaches that the bromination in the proposed method is conducted with addition of Br2 that is a brominating agent.
Claim 8 is obvious because Hulme teaches that the aromatization in the proposed method is conducted in the presence of Li2CO3.
Claim 12 and 21 are obvious because the product in the step of bromination in the proposed method forms the following compound
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which meets each and every limitation of the formula (IV) of claim 12 and 21 as R is OMe.
35 USC § 103 Rejection over a Combination of Rodo, Heller, Hulme, Heim, Kraus and Imaki
Claim 17 is rejected under 35 USC § 103 Rejection over a combination of E.C. Rodo, et al, Eur. J. Org. Chem. 1982–1993 (2016) (“Rodo”); H.G. Heller, US4931221 (1990) (“Heller”); A. N. Hulme, et al. J. Org. Chem. 60, 1265-1270(1995)(“Hulme”); R. Heim, et al. Journal of medicinal chemistry 51.16, 5064-5074 (2008)(“Heim”) and A. Kraus, Doctoral dissertation, (2008)(“Kraus”) as applied for claim 1 above further in view of S. Imaki, et al, JPH03279343A (1991)(“Imaki”).
The Combination of Rodo, Heller, Hulme, Heim and Kraus
As discussed above, the combination of Rodo, Heller, Hulme, Heim and Kraus teaches a method meeting each and every limitation of claim 1.
Difference between the Combination and Claim 17
The method taught by the combination differs from claim 17 in that the intramolecular cyclisation step in the proposed method is not conducted in the presence of the claimed acid.
S. Imaki, et al, JPH03279343A (1991)(“Imaki”) Imaki is published in Japanese, a copy of machine translation is attached as a second part of the reference, the full reference of Imaki has 13 pages, the format for citation of Imaki is xx/13.
Imaki teaches a method for producing a cyclic ketone with high selectivity and high yield in one step by intramolecularly cyclizing an aromatic substituted carboxylic acid with a small amount of an acid catalyst. Imaki at the last paragraph of page 08/13, Means for solving problem. Imaki also teaches that the preferred examples of the catalyst are trifluoromethanesulfonic acid and an anhydride thereof. Imaki at page 10/13, the second paragraph, line 5-6.
Obviousness Rationales of Claim 17
One ordinary skill in the art would arrive at the claimed invention before the effective filling date of the instant application because one ordinary skill in the art is motivated to further modify the above proposed method by conducting the step of the intramolecular cyclisation step with trifluoromethanesulfonic acid or its anhydride as the catalyst in view of the teaching from Imaki, thus arrive at a method meeting each and every limitation of claim 17. One ordinary skill in the art has a motivation to do so with a reasonable expectation of success because Imaki teaches that in the presence of trifluoromethanesulfonic acid or its anhydride cyclic ketone can be formed in one step by intramolecularly cyclizing an aromatic substituted carboxylic acid with high selectivity and high yield. The rationales are supported by “simple substitution of one known element for another to obtain predictable results”. MPEP 2143.I. B.
35 USC § 103 Rejection over a Combination of Rodo, Heller, Hulme, Heim, Kraus and Tanemura.
Claim 18 is rejected under 35 USC § 103 Rejection over a combination of E.C. Rodo, et al, Eur. J. Org. Chem. 1982–1993 (2016) (“Rodo”); H.G. Heller, US4931221 (1990) (“Heller”); A. N. Hulme, et al. J. Org. Chem. 60, 1265-1270(1995)(“Hulme”); R. Heim, et al. Journal of medicinal chemistry 51.16, 5064-5074 (2008)(“Heim”) and A. Kraus, Doctoral dissertation, (2008)(“Kraus”) as applied for claim 1 above further in view of K. Tanemura, et al, Chem. Commun. 470–471(2004)(“Tanemura”).
The Combination of Rodo, Heller, Hulme, Heim and Kraus
As discussed above, the combination of Rodo, Heller, Hulme, Heim and Kraus teaches a method meeting each and every limitation of claim 1.
Difference between the Combination and Claim 18
The method taught by the combination differs from claim 18 in that the brominating agent used in the proposed method is not NBS.
K. Tanemura, et al, Chem. Commun. 470–471(2004)(“Tanemura”)
Tanemura teaches a method of a-bromination of ketones with N-bromosuccinimide to give the corresponding a brominated ketones in good yields at mild condition. Tanemura at abstract. Per Table 2, Tanemura teaches that with his method 1-tetralone 9 can be brominated to give the a-brominated ketone 15 in 99% yield. Tanemura at page 470, Table 2, entry 6.
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Obviousness Rationales of Claim 18
One ordinary skill in the art would arrive at the claimed invention before the effective filling date of the instant application because one ordinary skill in the art is motivated to further modify the above proposed method by conducting the step of bromination with NBS as the brominating agent catalyzed by NH4OAc in Et2O at 25 °C as taught by Tanemura, thus arrive at a method meeting each and every limitation of claim 18, therefore, claim 18 is obvious. One ordinary skill has a motivation to do so with a reasonable expectation of success because the Tanemura method is conducted at mild condition and the yield of the desired product is high. The rationales are supported by “simple substitution of one known element for another to obtain predictable results”. MPEP 2143.I. B.
Allowable Subject Matter
Claims 4, 9 and 24 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
As mentioned in the above 103 rejection that the combination of Rodo, Heller, Hulme, Heim and Kraus teaches a method meeting each and every limitation of claim 1.
The proposed method differs from claim 4 in that none of the recited prior art teaches to prepare the Kraus 3-(4-methoxybenzyl)butanoic acid with the claimed method. Claim 4 is not obvious because one ordinary skill in the art is not motivated to further modify the claimed method by synthesis of the Kraus 3-(4-methoxybenzyl)butanoic acid with the claimed method with a reasonable expectation of success.
The proposed method differs from claim 9 in the oxidation step is not conducted in the presence of the claimed oxidizing agent. Claim 9 is not obvious because one ordinary skill in the art is not motivated to further modify the proposed method by conducting the oxidation step in the presence of the claimed oxidizing agent . Motivation lacks because Rodo teaches that while different oxidizing agents have been tried, only with Fremy's salt (2.8 equiv.)-KH2PO4 (0.8 equiv.) gave the desired product with good yield (99%).
As mentioned in the 102 rejection above that Hudkins teaches a compound meeting each and every limitation of claim 15, which differs from claim 24 in that the OCH2CH2CH2Cl group in the Hudkins compound is not the claimed CF3.
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Claim 24 is not obvious because neither Hudkins nor Hudkins in view a second prior art to motivate one ordinary skill in the art to elect the Hudkins compound and modify it by replacing the OCH2CH2CH2Cl with the claimed CF3.
Conclusion
Claims 1-3, 5-8, 10-23 are rejected, claims 4, 9, 16 and 24 are objected to. No claims are allowed.
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/FRANK S. HOU/Examiner, Art Unit 1692
/AMY C BONAPARTE/Primary Examiner, Art Unit 1692
Prosecution Insights