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 .
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 (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 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.
Claim(s) 1-4, 8, 11, 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Effenberger et al., U.S. Publication No. 2006/0160272, (“Effenberger”).
Claim 1
Effenberger discloses a process for producing 8-bromooct-1-ene. Effenberger prepares allylmagnesium bromide by adding allyl bromide to magnesium in diethyl ether and heating the resulting solution to boiling. Effenberger then introduces 1,5-dibromopentane in THF into a second flask, adds a Li₂CuCl₄ solution, transfers the allylmagnesium bromide into the dibromopentane-containing flask, and produces 8-bromooct-1-ene. Effenberger isolates the product in a reported 60% yield. See Effenberger ¶¶ [0076] and [0079]–[0085], publication pp. 3–4, particularly PDF text lines 431–434 and 442–480.
Effenberger therefore discloses:
• forming a reaction mixture comprising an alkyl dibromide, namely 1,5-dibromopentane;
• allylmagnesium bromide; and
• producing an alkenyl bromide, namely 8-bromooct-1-ene, in the reaction mixture.
Claim 1 further requires that the reaction mixture be “substantially free of Li₂CuCl₄.” The specification expressly defines this term as encompassing a reaction mixture containing no more than 1 wt.% copper, based on the elemental weight of copper present in the mixture. See the specification at ¶ [0038]. The special definition supplied by the specification is applied to the claim.
Effenberger employs only 0.05 mmol of Li₂CuCl₄. See ¶ [0079], publication p. 4, PDF text lines 443–449. Because each mole of Li₂CuCl₄ contains one mole of copper, the catalyst charge contains approximately 3.18 mg of elemental copper. The 2.17 mol of 1,5-dibromopentane alone corresponds to approximately 499 g. Using only the dibromopentane as the denominator gives a conservative maximum copper concentration of approximately 0.000637 wt.%, or 6.37 ppm. Inclusion of the ether, THF, magnesium, and Grignard reagent would reduce the calculated copper concentration further. Effenberger therefore falls well within the specification’s no-more-than-1-wt.% definition of “substantially free of Li₂CuCl₄.”
The fact that Effenberger deliberately adds a trace amount of Li₂CuCl₄ does not avoid anticipation because the claim, as defined by the specification, does not require the complete absence of Li₂CuCl₄. Accordingly, Effenberger discloses every limitation of claim 1.
Claim 2
Claim 2 further requires that the alkyl dibromide comprise a C₁–C₁₂ alkyl dibromide. Effenberger employs 1,5-dibromopentane, which is a C₅ alkyl dibromide and falls within the claimed range. See Effenberger ¶¶ [0079] and [0082], publication p. 4, PDF text lines 442–449 and 461–469.
Claim 3
Claim 3 requires an alkenyl bromide having the formula:
CH2=CH-CH2-(CH2)nBr
where n is an integer from 1 to 12.
Effenberger produces 8-bromooct-1-ene, having the structure:
CH2=CH-CH2-(CH2)5Br
and therefore satisfies the formula with n equal to 5. See Effenberger ¶¶ [0076], [0085], and [0087], publication pp. 3–4.
Claim 4
Claim 4 requires that the reaction mixture comprise the alkyl dibromide and allylmagnesium bromide. Effenberger expressly prepares allylmagnesium bromide from allyl bromide and magnesium in ether and transfers that Grignard reagent into the flask containing 1,5-dibromopentane. See Effenberger ¶¶ [0080] and [0082], publication p. 4, PDF text lines 450–454 and 461–469.
Claim 8
Claim 8 requires a molar ratio of alkyl dibromide to allylmagnesium reagent from 1.5:1 to 10:1. Effenberger employs 2.17 mol of 1,5-dibromopentane and allylmagnesium bromide prepared from 1.00 mol of allyl bromide, corresponding to a dibromide-to-Grignard ratio of 2.17:1. That value is within the claimed range. See Effenberger ¶ [0079], publication p. 4, PDF text lines 443–449.
Claim 11
Claim 11 requires an ether solvent and/or a hydrocarbon solvent. Effenberger uses 660 mL of diethyl ether and 200 mL of THF. Both are ether solvents. See Effenberger ¶ [0079], publication p. 4, PDF text lines 443–449.
Claim 13
Claim 13 requires separating at least a portion of the alkenyl bromide from the reaction mixture after production of the alkenyl bromide. Effenberger subjects the worked-up post-reaction mixture to fractional distillation over a 60-cm split-tube column and recovers pure 8-bromooct-1-ene. See Effenberger ¶¶ [0083]–[0085], publication p. 4, PDF text lines 470–480.
Claims 15–17 and 19 are rejected under AIA 35 U.S.C. § 102(a)(1) as anticipated by Mazerolles.
Claim 15
Mazerolles discloses preparing an allylmagnesium bromide solution in THF and adding pure 1-bromo-3-chloropropane to the stirred Grignard solution while maintaining the mixture at 50–60°C. Mazerolles thereafter boils the mixture for one hour and isolates 6-chloro-1-hexene in 82% yield. See Mazerolles, PDF p. 2, lines 43–61.
Mazerolles therefore expressly discloses:
forming a reaction mixture comprising a chlorobromoalkane, namely 1-bromo-3-chloropropane;
allylmagnesium bromide;
a contact temperature of 50–60°C, which is within the claimed 15–90°C range; and
producing an alkenyl chloride, namely 6-chloro-1-hexene, in the reaction mixture.
Mazerolles anticipates claim 15.
Claim 16
Claim 16 is satisfied when either the reaction-temperature limitation or the C₁–C₁₂ chlorobromoalkane limitation is met.
Mazerolles employs 1-bromo-3-chloropropane, a C₃ chlorobromoalkane falling within the claimed C₁–C₁₂ genus. Mazerolles also conducts the reaction at 50–60°C during addition and thereafter boils the THF-containing reaction mixture, thereby disclosing reaction conditions within the alternatively recited 30–70°C range. See Mazerolles, PDF p. 2, lines 50–54.
Because disclosure of one claimed alternative is sufficient for anticipation, Mazerolles anticipates claim 16.
Claim 17
Claim 17 requires that the reaction mixture comprise the chlorobromoalkane and allylmagnesium bromide. Mazerolles expressly combines 1-bromo-3-chloropropane with allylmagnesium bromide. See Mazerolles, PDF p. 2, lines 43–54.
Claim 19
Claim 19 is written in the alternative and is satisfied when at least one of the listed product, ratio, or selectivity limitations is present.
Mazerolles produces 6-chloro-1-hexene, which has the formula:
CH2=CH-CH2-(CH_2)3Cl
and therefore satisfies the first alternative of claim 19 with n equal to 3. See Mazerolles, PDF p. 2, lines 50–61. Mazerolles additionally describes the relevant haloalkenes by the general formula CH₂=CH–(CH₂)ₙX, where X may be chlorine or bromine. See PDF pp. 3–4, lines 96–111.
Mazerolles need not also disclose the separately recited reactant-ratio or selectivity alternatives because the claim joins the alternatives with “or.” Accordingly, Mazerolles anticipates claim 19.
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.
Claims 5–7 and 12 is/are rejected under 35 U.S.C. § 103 as unpatentable over Effenberger in view of Mazerolles, and further in view of Martin as to claim 5.
Effenberger discloses the underlying process of claim 1, including reacting an alkyl dibromide with an allylmagnesium reagent to produce an alkenyl bromide, as explained above. Effenberger does not expressly disclose the allylmagnesium chloride limitation of claim 5, the complete temperature limitations of claims 6 and 7, or the no-additional-solvent limitation of claim 12.
Mazerolles teaches a closely related carbon-carbon coupling between an allylmagnesium reagent and the bromide terminus of a dihaloalkane. Mazerolles adds pure 1-bromo-3-chloropropane directly to a stirred allylmagnesium bromide solution maintained at 50–60°C, completes the addition in approximately 30 minutes, and then boils the mixture for one hour to produce 6-chloro-1-hexene in 82% yield. See Mazerolles, PDF p. 2, lines 50–61. Mazerolles similarly produces 8-chloro-1-octene in 86% yield. Id. at lines 62–64.
Claim 5
Claim 5 requires that the reaction mixture comprise the alkyl dibromide and allylmagnesium chloride.
Effenberger teaches the claimed alkyl-dibromide-to-alkenyl-bromide process but uses allylmagnesium bromide. Martin establishes that allylmagnesium chloride was a known alternative allyl Grignard reagent for reaction with alkyl dihalides. Specifically, Martin combines 220 mmol of dibromoethane with 200 mmol of allylmagnesium chloride in THF, continues stirring after removal of the ice bath, and then refluxes the reaction mixture. See Martin ¶ [0214], publication p. 21, right column, and PDF text lines 2730–2736.
It would have been obvious to substitute Martin’s allylmagnesium chloride for the allylmagnesium bromide used by Effenberger. Both reagents provide the same nucleophilic allyl group, and Martin demonstrates that allylmagnesium chloride can be employed with an alkyl dibromide in the same type of chain-extension chemistry. The substitution is the use of one known allyl Grignard reagent in place of another known allyl Grignard reagent for its known carbon-carbon bond-forming function. Effenberger establishes that the dibromide reaction produces the alkenyl bromide, while Martin provides a reasonable expectation that the chloride form of the Grignard reagent would remain operative with an alkyl dibromide.
Accordingly, claim 5 would have been obvious over Effenberger in view of Martin. Mazerolles additionally confirms that reactions of allylmagnesium reagents with the bromide terminus of a dihaloalkane were known and operable without requiring the Grignard counter-halide to be incorporated into the organic product.
Claim 6
Claim 6 requires formation of the reaction mixture at a contact temperature from 15°C to 90°C and production of the alkenyl bromide at a reaction temperature from 15°C to 90°C.
Effenberger initially contacts the reactants at 0°C and thereafter brings the reaction mixture to room temperature and stirs overnight. Thus, Effenberger expressly discloses a reaction temperature within 15–90°C but does not disclose the claimed contact temperature. See Effenberger ¶ [0082], publication p. 4, PDF text lines 461–469.)
Mazerolles teaches adding a terminal bromo-substituted dihaloalkane to allylmagnesium bromide at 50–60°C and then boiling the mixture for one hour. Both the 50–60°C contact temperature and the approximate THF reflux temperature fall within the 15–90°C ranges of claim 6. See Mazerolles, PDF p. 2, lines 50–54.
It would have been obvious to conduct Effenberger’s corresponding coupling at the temperature successfully used by Mazerolles for reaction of an allylmagnesium reagent at the primary alkyl-bromide terminus of a dihaloalkane. The modification would eliminate the separate 0°C cooling operation and employ a known, operative elevated temperature that completed the analogous haloalkene-forming reaction in substantially less time than Effenberger’s overnight room-temperature reaction.
One of ordinary skill would have reasonably expected the modified Effenberger process to continue producing an alkenyl bromide because Effenberger independently establishes production of that product from the dibromide, while Mazerolles establishes that the underlying allylmagnesium/primary-alkyl-bromide coupling is operable at 50–60°C.
Mazerolles’s observation that dibromoalkanes may also form dienes does not preclude the rejection. Claim 6 requires production of the alkenyl bromide but does not impose a minimum yield, maximum diene amount, or minimum selectivity. Mazerolles, PDF pp. 3–4, lines 105–113.
Claim 7
Claim 7 requires that the alkenyl bromide be produced at a reaction temperature from 30°C to 70°C.
Mazerolles teaches maintaining the analogous allylmagnesium/dihaloalkane reaction at 50–60°C during addition and thereafter boiling the THF-containing mixture for one hour. The disclosed operating temperature lies within the claimed 30–70°C range. See Mazerolles, PDF p. 2, lines 50–54.
For the reasons stated for claim 6, it would have been obvious to employ Mazerolles’s known 50–60°C operating temperature in Effenberger’s process to accelerate the known coupling and avoid prolonged overnight reaction at room temperature, with a reasonable expectation that at least some of the required alkenyl bromide would be produced.
Claim 12
Claim 12 requires that no additional solvent be used and that solvent present in the reaction mixture originate from the allylmagnesium-halide solution.
Effenberger introduces 1,5-dibromopentane in 200 mL of THF and therefore uses additional solvent with the dibromide. See Effenberger ¶¶ [0079] and [0082], publication p. 4, PDF text lines 443–449 and 461–469.
Mazerolles teaches adding pure 1-bromo-3-chloropropane directly to the allylmagnesium bromide solution. No separate solvent is used to dissolve or carry the dihaloalkane; the solvent present during coupling is the solvent associated with the previously prepared allylmagnesium bromide solution. See Mazerolles, PDF p. 2, lines 43–54.
It would have been obvious to add Effenberger’s liquid 1,5-dibromopentane directly to the allylmagnesium-halide solution in the manner taught by Mazerolles. The modification would eliminate a separate solvent charge, reduce total reaction and workup volume, and retain the ether medium already supplied with the Grignard reagent. Mazerolles demonstrates that direct addition of an undiluted liquid dihaloalkane to an allylmagnesium solution is an operative process alternative. Claim 12 does not require any particular yield or selectivity resulting from omission of the additional solvent.
Accordingly, claims 5–7 and 12 would have been obvious over the applied references.
Claim 14 is/are rejected under 35 U.S.C. § 103 as being patentable over Effenberger in view of Suzuki.
For purposes of this rejection, claim 14 is interpreted as requiring separation of at least a portion of unreacted alkyl dibromide following step (b) and return of at least part of the separated alkyl dibromide to a reaction mixture formed in a subsequent performance of step (a).
Effenberger discloses fractionally distilling the post-reaction mixture and recovering both pure 8-bromooct-1-ene product and pure unreacted 1,5-dibromopentane. See Effenberger ¶¶ [0083]–[0084], publication p. 4, PDF text lines 470–478. Effenberger therefore teaches the claimed separation of the alkyl dibromide but does not expressly state that the recovered material is recycled.
Suzuki teaches separating unconverted 8-bromo-1-octene from the desired product by distillation and returning the separated, unconverted bromo compound to the reaction zone for complete conversion. See Suzuki, U.S. Patent No. 3,459,819, col. 2, lines 10–27, particularly lines 24–27.
It would have been obvious to return Effenberger’s recovered, pure 1,5-dibromopentane to a subsequent reaction batch. Suzuki establishes that returning a separated, unconverted halogenated organic reactant to its reaction zone was a known means for obtaining further conversion. Applying that known recycle technique to Effenberger would reuse the recovered dibromide for its original purpose, improve utilization of the starting material, and reduce the quantity of fresh dibromide required. No change in the chemical function of the recovered material would be required.
Accordingly, claim 14 would have been obvious over Effenberger in view of Suzuki.
Claims 18 and 20 is/are rejected under 35 U.S.C. § 103 as unpatentable over Mazerolles in view of Martin.
Mazerolles discloses every limitation of claim 15, as explained above, but employs allylmagnesium bromide. Martin teaches the corresponding use of allylmagnesium chloride with the same chlorobromoalkane and production of the same alkenyl chloride.
Claim 18
Martin’s Example 2 combines 152 mmol of 1,3-bromochloropropane with 160 mmol of allylmagnesium chloride in THF and produces 6-chlorohex-1-ene. See Martin ¶ [0210], publication p. 21, left column, PDF text lines 2663–2678.
It would have been obvious to substitute Martin’s allylmagnesium chloride for the allylmagnesium bromide used by Mazerolles. Martin demonstrates the substitution using:
the exact same 1-bromo-3-chloropropane substrate;
the same desired 6-chlorohex-1-ene product; and
the same allylmagnesium chain-extension reaction.
The only material reagent difference is the halide associated with magnesium. Martin expressly establishes that allylmagnesium chloride performs the required reaction and produces the required product. One of ordinary skill therefore would have had a reasonable expectation of success in using allylmagnesium chloride in Mazerolles’s temperature-compliant process.
Accordingly, claim 18 would have been obvious over Mazerolles in view of Martin.
Claim 20
Claim 20 requires an alkenyl-chloride molar yield of at least 50%, based on the allylmagnesium reagent, and no more than 15 mol% diene by-product on the same basis.
Mazerolles starts with allylmagnesium bromide prepared from 1.50 mol of allyl bromide and obtains 0.78 mol of 6-chloro-1-hexene. Even assuming quantitative formation of the Grignard reagent, the product amount corresponds to 52 mol% based on the maximum possible 1.50 mol of allylmagnesium bromide. Any less-than-quantitative formation of the Grignard reagent would increase, rather than decrease, the product yield calculated on the actual Grignard basis. Mazerolles therefore teaches an alkenyl-chloride yield of at least 50 mol% on the claimed basis. See Mazerolles, PDF p. 2, lines 34–40 and 50–61.
Mazerolles does not expressly quantify a diene by-product. Martin, however, performs the exact 1,3-bromochloropropane/allylmagnesium-chloride reaction and reports:
160 mmol of allylmagnesium chloride;
an 82% product yield;
a residue containing 80% 6-chlorohex-1-ene; and
only 3% 1,8-nonadiene.
See Martin ¶ [0210], publication p. 21, left column, PDF text lines 2665–2678.
Martin’s reported product-to-diene composition ratio is approximately 26.7:1. Further, if the reported 3% is treated conservatively as 3 wt.% of the reported 18.55-g crude material, the diene amount is approximately:
18.55g x 0.03=0.5565g diene
Using a molecular weight of approximately 124.23 g/mol for 1,8-nonadiene gives approximately 4.48 mmol of diene. Relative to 160 mmol of allylmagnesium chloride, this corresponds to approximately 2.8 mol%, well below the claimed 15 mol% ceiling.
It would have been obvious to employ Martin’s allylmagnesium chloride and its demonstrated low-diene reaction conditions in Mazerolles’s process because Martin uses the exact same chlorobromoalkane and produces the exact same alkenyl chloride while demonstrating both high product yield and low diene formation. Mazerolles establishes that the same substrate/product reaction is successfully conducted at a contact temperature within claim 15, and Martin establishes that substitution of allylmagnesium chloride produces the claimed high-yield, low-diene result.
The modification represents the use of a known reagent and known conditions for their demonstrated function in the same chemical reaction, with a reasonable expectation of obtaining the reported high product yield and suppressed diene formation. Accordingly, claim 20 would have been obvious over Mazerolles in view of Martin.
The rejection of claim 20 is made under § 103 rather than § 102 because Martin does not expressly characterize its reported 80% and 3% analytical values as molar percentages calculated on the starting allylmagnesium-chloride basis. Martin nevertheless supplies direct experimental evidence from the exact reactant/product system that the claimed high-yield and low-diene operating region was attainable.
Claims 9 and 10 are rejected under 35 U.S.C. § 103 as unpatentable over Effenberger et al., U.S. Publication No. 2006/0160272, in view of Martin et al., U.S. Publication No. 2013/0035458, and further in view of Johnson et al.
Claim 9
Effenberger discloses the process of claim 1, including reacting 1,5-dibromopentane with allylmagnesium bromide to produce 8-bromooct-1-ene. Effenberger employs 1.00 mol of allyl bromide to prepare the allylmagnesium bromide and obtains 602 mmol of 8-bromooct-1-ene, corresponding to a 60 mol% yield based on the allylmagnesium bromide. Effenberger therefore satisfies claim 9’s requirement of an alkenyl-bromide yield of at least 50 mol%. Effenberger also identifies 1,10-undecadiene as the competing diene product but does not quantify its amount. See Effenberger, paragraphs [0079]–[0085], publication page 4.
Martin teaches that the closely analogous reaction of a dihaloalkane with an allylmagnesium halide can be conducted with both high desired-product yield and little diene formation. Specifically, Martin reacts 1,3-bromochloropropane with allylmagnesium chloride and reports an 82% yield of 6-chlorohex-1-ene, with the product-containing residue analyzing as 80% 6-chlorohex-1-ene and only 3% 1,8-nonadiene. See Martin, paragraph [0210], publication page 21.
Johnson further teaches that allylmagnesium bromide reacts with α,ω-dihaloalkanes to produce either mono-coupled haloalkenes or di-coupled alkadienes depending upon the selected reaction conditions. Johnson’s mono-coupling experiments use shorter reaction times and lower temperatures, whereas the diene-producing experiments require longer reaction times and generally higher reaction temperatures. Johnson therefore establishes that the reaction conditions were recognized to control the mono-coupled-product/diene distribution. See Johnson, pages 1557 and 1559–1560.
It would have been obvious to one having ordinary skill in the art before the effective filing date to select and optimize Effenberger’s reaction conditions to favor the desired mono-coupled alkenyl bromide and suppress the known diene by-product. Effenberger expressly identifies both the desired alkenyl bromide and the competing diene, Johnson establishes that their relative formation depends on the selected reaction conditions, and Martin demonstrates that the analogous allylmagnesium-halide/dihaloalkane coupling can provide greater than 50% desired product while limiting the diene to an amount substantially below 15%.
The motivation would have been to increase the yield and purity of the desired alkenyl halide, reduce consumption of Grignard reagent through double coupling, and simplify product purification. Martin provides a reasonable expectation that selection of mono-coupling-favoring conditions would produce the claimed high-yield, low-diene result.
Accordingly, the process of claim 9 would have been obvious over Effenberger in view of Martin and Johnson.
Claim 10
Effenberger teaches production of 8-bromooct-1-ene and identifies 1,10-undecadiene as the competing double-coupling product but does not quantify the product-to-diene ratio.
Martin reports, in the analogous allylmagnesium-chloride/dihaloalkane reaction, a product-containing residue having 80% alkenyl chloride and 3% diene. These values correspond to an analytical product-to-diene ratio of approximately 26.7:1 and, if the percentages are weight-based, a molar ratio of approximately 27.9:1. Either calculation falls within the broadly claimed range of 5:1 to 250:1. See Martin, paragraph [0210], publication page 21.
Johnson teaches that reaction conditions determine whether the process favors the mono-coupled haloalkene or the di-coupled diene and that the conditions employed to form the mono-coupled products differ from the longer and higher-temperature conditions used to form the dienes.
It would have been obvious to optimize the known Effenberger process toward the mono-coupled product because Johnson expressly identifies the reaction conditions as controlling the mono-coupling/double-coupling outcome, and Martin demonstrates that the resulting product-to-diene relationship can fall well within the claimed range. Selection of conditions favoring the desired product over a known competing by-product constitutes optimization of recognized result-effective variables. The USPTO recognizes that where the prior art identifies a relationship between a variable and the relevant result, the variable is result-effective and optimization ordinarily supports a prima facie case of obviousness.
Accordingly, claim 10 would have been obvious over Effenberger in view of Martin and Johnson.
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 1-2, 4-20 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 1, 2, and 4–20 are rejected under 35 U.S.C. § 112(a) because the specification, while being enabling for processes employing the limited terminal, linear dihalides exemplified in the disclosure, does not reasonably enable a person having ordinary skill in the art to make and use the full scope of the claimed invention without undue experimentation.
The test for compliance with the enablement requirement is whether the disclosure, as originally filed, would have enabled a person having ordinary skill in the art to make and use the full scope of the claimed invention without undue or unreasonable experimentation. Whether the necessary experimentation is undue is determined by considering the factors set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The Wands factors remain applicable following Amgen Inc. v. Sanofi, 598 U.S. 594 (2023), and the specification must enable the full scope of the claimed class, although a reasonable amount of experimentation is permissible. MPEP §§ 2164.01, 2164.01(a), and 2164.08. (USPTO)
Claim 1 broadly recites forming a reaction mixture comprising “an alkyl dibromide” and allylmagnesium bromide, allylmagnesium chloride, or a combination thereof, and producing an alkenyl bromide. Claim 15 similarly recites forming a reaction mixture comprising “a chlorobromoalkane” and the recited allylmagnesium reagent and producing an alkenyl chloride. Claims 1 and 15 do not limit the carbon-chain length, positions of the halogen atoms, degree of branching, substitution at the carbon atoms bearing the halogens, or relative positions of the bromine and chlorine atoms. Claim 2 limits the alkyl dibromide to a C₁–C₁₂ alkyl dibromide, but continues to encompass the numerous positional and structural variants within that carbon-number range. Claim 16 does not cure the deficiency because its alternatives permit the claim to be satisfied solely by the recited reaction temperature without limiting the structure of the chlorobromoalkane. The remaining rejected dependent claims likewise retain the broad substrate genera of claims 1 or 15.
The disclosure states that the alkyl dibromide and chlorobromoalkane are “not particularly limited” and may be linear or branched. However, the working disclosure is directed principally to terminal, linear substrates, including 1,2-dibromoethane, 1,3-dibromopropane, 1-bromo-2-chloroethane, and 1-bromo-3-chloropropane. The specification does not provide representative examples involving geminal dihalides, internally positioned dihalides, secondary or tertiary bromides, or substantially branched substrates. Nor does the specification provide a generally applicable structure-reactivity rule by which a skilled artisan could determine, without testing, whether a particular member of the claimed genera will undergo the required allylation while retaining the bromine or chlorine atom necessary to form the claimed alkenyl halide. Paragraphs [0030]–[0032] describe the genera broadly, whereas the experimental discussion in paragraphs [0055]–[0065] is substantially narrower.
The following Wands factors have been considered.
(A) Breadth of the claims
The claims are substantially broader than the specifically demonstrated subject matter. Claims 1 and 15 encompass structurally diverse alkyl dibromides and chlorobromoalkanes without limiting the carbon skeleton, positions of the halogens, degree of substitution, or chain length. Claim 2 encompasses the full range of C₁–C₁₂ alkyl dibromides, including positional and branched isomers. Claims 9, 10, 19, and 20 further define portions of these broad genera functionally by requiring particular yields, diene amounts, or selectivity ratios, without structurally identifying which substrates or combinations of reaction conditions provide those results.
(B) Nature of the invention
The invention concerns a selective chemical reaction between a highly reactive allylmagnesium reagent and a polyhalogenated organic substrate. Successful practice requires reaction at one carbon-halogen site while retaining another halogen atom in the alkenyl product and limiting competing formation of diene products. The desired result therefore depends upon chemoselectivity, substrate structure, Grignard reagent identity, solvent, temperature, reactant ratio, and reaction time.
(C) State of the prior art
Grignard reagents and standard methods for conducting and analyzing Grignard reactions were known. This factor favors enablement to a limited extent. However, the present record does not establish that all positional, branched, geminal, internal, secondary, and tertiary members encompassed by the claimed dihalide genera were known to undergo the claimed selective reaction under the disclosed conditions. The specification does not identify a recognized general principle in the art that would permit the skilled artisan to extrapolate the results obtained for the limited terminal, linear examples across the entire claimed scope.
(D) Level of ordinary skill in the art
A person having ordinary skill in the art would be expected to possess substantial knowledge of synthetic organic chemistry, Grignard-reagent handling, reaction workup, and chromatographic analysis. This relatively high level of skill weighs in favor of enablement. Nevertheless, ordinary skill does not supply the missing structure-reactivity relationship or permit the artisan to predict, from the disclosure alone, whether each materially different dihalide substrate will undergo selective monoallylation, elimination, multiple substitution, coupling, decomposition, or another competing reaction.
(E) Predictability of the art
The disclosure itself demonstrates that the reaction outcome is sensitive to changes in the reaction variables. Paragraphs [0055]–[0065] report materially different alkenyl-halide yields and diene formation depending upon whether allylmagnesium bromide or allylmagnesium chloride is used, whether the substrate is a dibromide or chlorobromoalkane, the length of the dihalide, the solvent, the reaction temperature, the reactant ratio, and the reaction time. For example, paragraph [0055] reports substantially different yields and diene formation for allylmagnesium chloride and allylmagnesium bromide under otherwise corresponding conditions; paragraph [0057] reports that dihalide chain length affects yield; and paragraphs [0060]–[0065] report differing temperature and time effects. These results establish that successful reaction conditions cannot reliably be extrapolated throughout the claimed structural scope merely from the limited examples.
(F) Amount of direction or guidance supplied
The specification supplies useful general guidance regarding reagent identity, temperature, reaction time, solvent, reactant ratio, workup, yield, and selectivity. See, for example, paragraphs [0034]–[0049]. The specification does not, however, provide guidance for selecting operative reaction conditions based upon the location or substitution of the halogen-bearing carbon atoms. It does not explain how the disclosed procedure is to be modified for structurally different members of the claimed genera or identify which structural classes are unsuitable. The supplied guidance is therefore directed primarily to optimizing the limited substrate types tested rather than enabling the full structural scope claimed.
(G) Existence of working examples
Working examples are provided for a limited number of terminal, linear dihalides. Those examples establish that at least some embodiments are enabled and preclude a finding that no embodiment can be practiced. They do not constitute representative examples across the materially broader structural scope of claims 1, 2, and 4–20. The examples do not demonstrate the claimed reaction for the numerous untested positional, substitutional, and branched variants encompassed by the claims.
(H) Quantity of experimentation required
To practice the full scope, a skilled artisan would be required to select each materially different dihalide substrate and determine experimentally whether it produces the required alkenyl halide. For each substrate, the artisan may be required to screen allylmagnesium bromide and allylmagnesium chloride, solvent systems, contact temperatures, reaction temperatures, reactant ratios, and reaction times. For claims 9, 10, 19, and 20, the artisan would additionally be required to quantify product yield and diene formation to determine whether the functional limitations are satisfied. Such experimentation would not merely optimize a known operative embodiment; it would identify which members of the broadly claimed genera are operative and which reaction conditions cause them to satisfy the claimed result. The required substrate-by-substrate and condition-by-condition screening is undue when considered in relation to the breadth of the claims and the limited structural guidance supplied.
Considering the evidence as a whole, the disclosure does not establish that the limited terminal, linear examples can reasonably be extrapolated to the full scope of the alkyl-dibromide and chlorobromoalkane genera. A person having ordinary skill in the art would therefore have been required to undertake undue experimentation to identify the operative members and conditions encompassed by claims 1, 2, and 4–20.
Claim 3 is not included in this rejection because it limits the produced alkenyl bromide to the homologous formula CH₂=CH–CH₂–(CH₂)ₙBr, wherein n is an integer from 1 to 12, which materially narrows the structural scope relative to the unrestricted alkyl-dibromide genus.
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 9-10, 14, 19-20 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.
Claims 9 and 20 recite a “molar amount of diene by-product” that is less than or equal to 15%. Claims 10 and 19 recite a molar selectivity ratio of the respective alkenyl halide to “a diene by-product.” The identity and scope of the recited “diene by-product” are unclear.
The specification does not identify the diene by-product by chemical name, structural formula, molecular formula, chromatographic retention characteristic, or other objective criterion. Paragraph [0046] refers to a molar amount of “diene by-products” in the plural, whereas paragraph [0047] refers to the selectivity of the alkenyl halide relative to “the diene by-product” in the singular. The experimental discussion similarly reports increases or decreases in “diene by-product” without identifying the particular compound or compounds included in that measurement.
It is therefore unclear whether the limitation encompasses:
the combined molar amount of every diene-containing compound formed in the reaction;
the amount of a single predominant diene;
the amount of a particular but unidentified diene species;
the amount of each diene species considered individually; or
an applicant-selected diene species.
These interpretations produce materially different claim boundaries. For example, a reaction mixture containing several diene species could satisfy the 15% limitation when each diene is considered separately but fail the limitation when the diene species are aggregated. Similarly, the selectivity ratio could differ substantially depending upon whether the denominator is the amount of one diene or the combined amount of all diene by-products. Neither the claims nor the specification provides an objective basis for selecting among these interpretations.
Accordingly, a person having ordinary skill in the art would not be reasonably apprised of the compounds that must be included in the claimed diene amount or in the denominator of the claimed selectivity ratio. Claims 9, 10, 19, and 20 are therefore indefinite.
The rejection may be overcome by amending the claims to identify the relevant diene structurally or to state expressly that the limitation is calculated using the combined molar amount of all diene-containing reaction by-products, together with an objective method for determining that amount.
Claim 14 recites “separating at least a portion of the alkyl dibromide from the reaction mixture after step (b), and recycling into the reaction mixture in step (a).”
The recitation “and recycling into the reaction mixture” does not identify the material being recycled. Although the separated alkyl dibromide may have been intended, the claim does not expressly require recycling the separated portion, all of the separated alkyl dibromide, a stream containing the alkyl dibromide, or another material obtained from the separation operation.
The temporal relationship of the recycling step is also unclear. Claim 1 requires formation of the reaction mixture in step (a), followed by production of the alkenyl bromide in step (b). Claim 14 thereafter requires separation of the alkyl dibromide after step (b), but recites recycling material into “the reaction mixture in step (a).” It is unclear whether the separated material is:
returned to the same reaction mixture after completion of step (b);
returned during a repetition of step (a) in a subsequent batch;
introduced into a continuously operating reaction mixture; or
used to form a separate reaction mixture in a later performance of the process.
Paragraphs [0049] and [0089] disclose optional separation and recycling into the reaction mixture, but repeat substantially the same language and do not resolve whether the recycling occurs in the same process cycle, a subsequent process cycle, or a continuous process.
Because these interpretations require materially different process operations, the metes and bounds of claim 14 cannot be determined with reasonable clarity. Claim 14 is therefore indefinite.
The rejection may be overcome by amending the claim, for example, to recite:
“…separating at least a portion of the alkyl dibromide from the reaction mixture after step (b), and recycling at least part of the separated alkyl dibromide into a reaction mixture formed during a subsequent performance of step (a).”
Alternatively, when a continuous process is intended, the claim should identify the separated recycle stream and the process location at which that stream is returned.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEBORAH D CARR whose telephone number is (571)272-0637. The examiner can normally be reached Monday-Friday (10:30 am -6:30 pm).
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/DEBORAH D CARR/Primary Examiner, Art Unit 1691
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