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. Election/Restrictions Applicant’s election without traverse of Group I, encompassed by claims 1-8 in the reply filed on March 5 , 2026 is acknowledged. Claim s 9-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected FILLIN "Enter the appropriate information" \* MERGEFORMAT invention , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 5 , 2026 . Application and Claims Status Claims 1-10 were pending. In the amendment as filed on March 5 , 2026 , applicants have amended claim 1 and 10 ; withdrew claims 9-10; cancelled no claims; and added no new claims . Therefore, claims 1-8 are currently pending . Additionally, the present specification is amended in order to : “amend the reaction route” to correct a structure error from a benzoate ester to a nicotinate ester. Priority The instant application is a national phase entry of International Application No. PCT/CN20 22 / 087601 , filed April 19, 2022 , which claims priority to Chinese patent application No. 202110432773.7, filed April 21, 2021 . Information Disclosure Statement The information disclosure statements (IDS) filed on October 23, 2023 and March 9, 2026 are in compliance with the provisions of 37 CFR 1.97. All references have been considered except where marked with a strikethrough. A signed copy of Form 1449 is included with this Office Action. Specification - Drawings Acknowledgement is made of the drawings received October 23, 2023 . These drawings are acceptable . Specification – Disclosure On page 2, line 5 of the instant specification, Applicant makes a reference to the prior art Organic Syntheses procedure, published in 1998. Applicant reports that the reference teaches the synthesis of racemic nicotine, when in fact, the reference teaches the synthesis of 2-phenyl-1-pyrroline and other derivatives that do not include nicotine or a derivative thereof. Appropriate correction is required. The specification recites the following metal catalysts as, “ Rh(COD)C l 2 , lr (COD)Cl 2 ”, and the chemical formulae for these are incorrect (Page 7, line 16; page 8, line 30; page 11, line 8) . They should properly be “[Rh(COD)Cl] 2 , [ Ir (COD)Cl] 2 ”. Appropriate correction is required. The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which applicant may become aware of in the specification. Claim Interpretation Applicant uses the term “feeding mass ratio ” in instant claim 6 and in embodiments of the instant disclosure. However, there is no standard defined term in the art and no definition is provided in the specification either. The Examiner is interpreting “feeding mass ratio” to mean a weight-to-weight ratio, by mass, of components of a reaction. So, for instance, if 50 kg of compound A is added to a reaction vessel, and 10 kg of compound B is added to a reaction vessel, the “feeding mass ratio” of compound A:B is 50:10, or simply 5:1. Claim Objections Claim 7 is objected to for the following reason: the claim recites the following metal catalysts as, “ Rh(COD) C l 2 , lr (COD)Cl 2 ”, and the chemical formulae for these are incorrect. They should properly be “[Rh(COD)Cl] 2 , [ Ir (COD)Cl] 2 ”. Appropriate correction is required. Claim Rejections - 35 USC § 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. 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 appl icant regards as his invention. Claim 8 is 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. Regarding claim 8, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase “preferably” are part of the claimed invention. See MPEP § 2173.05(d). 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). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu , 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by “such as” and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald , 131 USPQ 74 (Bd. App. 1961); Ex parte Hall , 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche , 86 USPQ 481 (Bd. App. 1949). In the present instance, claim 8 recites the broad recitation “formaldehyde” and the claim also recites “e.g., an aqueous formaldehyde solution”, which is the narrower statement of the range/limitation. 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 § 112(a) 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 7-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for the preparation of a single enantiomer of L-nicotine using [ Ir (COD)Cl ] 2 and L2 (BINAP) as the catalyst and ligand combination, does not reasonably provide enablement for the preparation of a single enantiomer of L-nicotine using all of the catalysts and all of the ligands recited in claim 7. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims . To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation . In re Wright , 999 F.2d 1557, 1561 ( Fd . Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that: The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt , 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation". The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands , 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman , 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors: 1- the quantity of experimentation necessary, 2- the amount of direction or guidance provided, 3- the presence or absence of working examples, 4- the nature of the invention, 5- the state of the prior art, 6- the relative skill of those in the art, 7- the predictability of the art, and 8- the breadth of the claims These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher , 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons: The nature of the invention and state of the prior art : The instant claims 1-8 are drawn to a preparation method for L-nicotine, wherein in step 3, myosmine is subjected to an enantioselective asymmetric hydrogenation in the presence of a catalyst generated in situ , with metal catalysts includ ing [ Rh(COD)C l ] 2 , [ lr (COD) C l ] 2 , Ru(COD) C l 2 , PdCl (PPh 3 ) 3 , PdCh (PPh 3 ) 2 , Ni( acac ) 2 , Ni Cl 2 , and Ni(COD) 2 and a ligand including L1 through L6 (as recited in claim 7) ; and further methylation to obtain L-nicotine. Instant claim 7 , as recited, is a reach through claim. A reach through claim is a claim drawn to an overall transformation in general format and thereby reach through a scope of invention for which they lack adequate written description and enabling disclosure in the specification. In the instant cas e, Applicant only demonstrates the asymmetric hydrogen of myosmine using [ lr (COD)C l ] 2 and L2 and instant claim reach es through for a process for asymmetric reduction of myosmine using any or all metal catalysts and ligand combinations for which there is no enabling disclosure. More specifically, the process for asymmetric reduction of a pyridyl-a p pended cyclic N-alkyl imine (of which myosmine categorically is) remains poorly developed. As recent as 2025, Yang et al. (Org. Lett., published 2025) writes , on page 2564 , “ t he AH [asymmetric hydrogenation] of pyridyl-appended cyclic N -alkyl imines using transition metal or other types of catalysis remains poorly developed. This is partly attributed to the strong coordination of the pyridine unit, leading to deactivation of the catalyst …no catalysts other than biocatalysts (enzymes) have been reported for the direct AH of myosmine to form S - nornicotine .” Examiner notes that the S enantiomer is the same as the L enantiomer for L-nicotine, and S - nornicotine is the demethylated precursor to L-nicotine. Specification has no teaching or suggestion as to viability of the process for the asymmetric reduction of myosmine with any or all catalyst and ligand systems, specifically [ Rh(COD)C l ] 2 , Ru(COD)C l 2 , PdCl (PPh 3 ) 3 , PdCh (PPh 3 ) 2 , Ni( acac ) 2 , Ni Cl 2 , and Ni(COD) 2 and a ligand including L 1 and L3-L 6 . Predictability of the art : Hence, the process as applied to the above-mentioned compounds claimed by the applicant is not an art-recognized process and hence there should be adequate enabling disclosure in the specification with working example(s). Level of skill in the art : An ordinary artisan in the area of process development would have experience screening metal/ligand systems and synthesizing chemical compounds for particular chemical transformations , such as a synthetic or process chemist . Thus, the level of skill in the art is high. The breadth of the claims : The s pecification has no support, as noted above, making compound L- nictoine via asymmetric hydrogenation and methylation in the presence of any or all catalyst and ligand systems in claim 7 . There is no showing that the process embraced in claim 7 with any catalyst and ligand would lead to desired S - nornicotine . The specification only demonstrates the use of [ lr (COD)C l ] 2 and L2 in order to reduce myosmine asymmetrically. The amount of direction provided, the presence or absence of working examples, and the quantity of experimentation necessary : Example 3 in Specification (Page 11, lines 6-19) shows the process for the preparation of L-nicotine using [ lr (COD)C l ] 2 and L2 from myosmine . It does not show such a process with any other catalyst or ligand system. Furthermore, it is well-known in the art that asymmetric hydrogenation of pyridyl-appended cyclic N -alkyl imines using transition metal or other catalysts is poorly developed. In fact, no catalysts, other than enzymes, have been reported for direct asymmetric hydrogenation of myosmine to form S - nornicotine (and thus L-nicotine) . Hence, this example is limited to make S - nornicotine (and thus L-nicotine) using [ lr (COD)C l ] 2 and L2. The quantity of experimentation needed would be an undue burden on skilled art in the chemical art since there is inadequate guidance given to the skilled artisan for the many reasons stated above. Also, note MPEP 2164.08(b) which states that claims that read on "... significant numbers of inoperative embodiments would render claims nonenabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.". Clearly that is the case here. Thus, factors such as “sufficient working examples”, the “level of skill in the art and predictability, etc. have been demonstrated to be sufficiently lacking in the case for the instant claims. Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p] atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable". MPEP §2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was ‘filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here and undue experimentation will be required to practice Applicants’ invention. Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success. Claim 8, which is dependent on claim 7, is also rejected for further requiring and/or reciting elements that are outside the scope of the enabling elements listed above. 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. Claim(s) 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Arnold ( US 2017/0112182 A1, effectively filed October 23, 2015, on Applicant IDS submitted March 9, 2026 ) (hereinafter “Arnold”) , in view of Jiaquan et al. (CN112409327A, effectively filed on November 18, 2020, on Applicant IDS submitted October 23, 2023)(hereinafter “ Jiaquan ”) as evidenced by Sorgi et al. ( Org. Synth., 1998, Vol. 75, p. 215 , published 1998, on Applicant IDS submitted October 23, 2023)(hereinafter “ Sorgi ” ). Regarding claim 1 : Arnold teaches (Specification, Example 1, pages 10 , among other Examples as well ) the condensation of 2-vinylpyrrolidone with ethylnicotinate to form 3-nicotinoyl-1-vinyl-4, 5-dihydro-1H-pyrrole-2-potassium alcoholat e. The 3-nicotinoyl-1-vinyl-4, 5-dihydro-1H-pyrrole-2-potassium alcoholat e is refluxed in dilute HCl, and after cooling, a base is added to form mysomine intermediate. Mysomine is reduced on Pd/C with hydrogen gas. Last, the compound is methylated via reductive amination using formaldehyde. Arnold’s general synthetic sequence (Specification Scheme 1, page 4) is nicely outlined below : There are two things the Examiner wants to note here. First, Applicant obtains a compound of formula II and explicitly draws it in instant claim 1. Reference application does not expressly show this . In fact, most prior art, after condensation of 2-vinylpy r rolidone to form 3-nicotinoyl-1-vinyl-4, 5-dihydro-1H-pyrrole-2-potassium alcoholat e, perform a two-step, one-pot reaction of refluxing in acid, and following this, adjusting the pH to basic conditions, to directly obtain myosmine , without isolation of an intermediate such as a compound of formula II. However, in reference application, a compound of formula II is inherently present since it is the direct product of refluxing 3-nicotinoyl-1-vinyl-4, 5-dihydro-1H-pyrrole-2-potassium alcoholat e in acid, which undergoes a ring-opening and decarboxylation to form a compound of formula II. In fact, Arnold states, on page 5, para 0023, that after acid is added to the condensation reaction mixture, “the aqueous reaction mixture is comprised of water, acid, and product (i.e. the protonated acyclic amine salt, e.g., protonated 3-(4-aminobutanyl-1-one)-pyridine).” The 3-(4-aminobutanyl-1-one) - pyridine species referenced by Arnold is indeed the same compound of formula II in instant claim 1. Furthermore, i n Sorgi’s synthesis of a phenyl version of myosmine (page 215, reaction scheme, shown below), he teaches (page 216, under Discussion), “an advantage of this method is to use the readily available, inexpensive N-vinyl-pyrrolidin-2-one as a key starting material. This compound serves effectively as a 3-aminopropyl carbanion equivalent.” Thus, it is quite clear that, while Arnold does not explicitly draw out a compound of formula II, it is obtained by Arnold. Second , the reference document synthesizes racemic R,S -nicotine, and does not isolate a single enantiomer. However, c laim 1 of instant application does not specify that L-nicotine was “isolated”, but rather, the Applicants “obtain L-nicotine”. Indeed, reference document also obtains L-nicotine, as it is inherently present in the racemic mixture. A person of ordinary skill in the art would recognize that a racemate is a 50:50 mixture of the two enantiomers of a compound. Thus, since Arnold discloses a racemic mixture of nicotine, then the L-enantiomer of nicotine also exists. Indeed, the Courts have ruled on cases of racemates versus enantiomers. They ruled that the reference does not have to suggest resolution of the racemate. One skilled in the art is presumed to be able to do so. The expectation with regard to enantiomers is that activities as they pertain to living systems are expected to be different. In re Adamson, 275 F.2d 952, 125 U.S. P.Q. 233 (C.C.P.A. 1960). Therefore, a rejection of claim 1 only requires that racemic R,S-nicotine is prepared in a reference document via the same synthetic sequence as instant application. However, Examiner would like to further support his position. Jiaquan teaches the asymmetric reduction of myosmine to achieve S - nornicotine (the penultimate product before methylation to obtain L-nicotine) . Jiaquan performs a catalytic reaction by an enzyme system (see reference Specification, Examples 1-6, para 0065-0076). A claimed embodiment of the biological enzyme system comprises glucose dehydrogenase and an imine reductase (reference claim 1, part d, subsection 9). Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to combine the known synthetic preparation of Arnold with the asymmetric mysomine reduction of Jiaquin to yield the predictable result of chiral L-nicotine. All the claimed elements are known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. One of ordinary skill would find motivation in that Jiaquin teaches the chiral reduction of mysomine , which is an intermediate in the synthetic sequence taught by Arnold. Regarding claim 2 , it would have been obvious to use a base in step (1), where the compound of formula I is subjected to a substitution reaction with N-vinylpyrrolidone, wherein the base is selected from potassium hydroxide, sodium hydroxide, potassium tert-butoxide , sodium ethoxide, potassium carbonate, sodium hydride, butyl lithium, and methylmagnesium bromide because Arnold teaches the use of a base, specifically sodium hydride, at this same synthetic step (page 11, Synthesis Example 5, para 0076). Regarding claim 3 , it would have been obvious to use a reaction solvent in step (1), where the compound of formula I is subjected to a substitution reaction with N-vinylpyrrolidone, in a solvent selected from toluene, xylene, tetrahydrofuran, ethanol, 2-methyltetrahydrofuran, and n-hexane because Arnold teaches the use of a solvent, specifically toluene, at this same synthetic step (page 11, Synthesis Example 5, para 0076). Regarding claim 4 , it would have been obvious to use an acid in step (1) for the decarboxylation reaction, wherein the acid is selected from hydrochloric acid, phosphoric acid, sulfuric acid, formic acid, and acetic acid , because Arnold teaches the use of an acid, specifically hydrochloric acid, at this same synthetic step (page 11, Synthesis Example 5, para 0076). Regarding claim 5 , it would have been obvious to use a base in step (2), where the compound of formula II is subjected to a cyclization, wherein the base is selected from potassium hydroxide, sodium hydroxide, potassium tert-butoxide, sodium ethoxide, potassium carbonate, sodium hydride, triethylamine, butyl lithium, and methylmagnesium bromide because Arnold teaches the use of a base, specifically sodium hydroxide, at this same synthetic step (page 11, Synthesis Example 5, para 0076). Moreover, it would have been obvious to use as a reaction solvent in step (2), wherein the solvent is selected from water, ethyl acetate, dichloromethane, N,N - dimethylformamide, tetrahydrofuran, ethanol, 2-methyltetrahydrofuran, n-hexane, and methyl tert-butyl ether because Arnold teaches the use of a solvent, specifically water , at this same synthetic step (page 11, Synthesis Example 5, para 0076). Regarding claim 6 , the claim language around “feeding mass ratio” is language around amounts and concentrations of reaction components. The instant claim reports a range of ratios between reaction solvent and the compound of formula II in step (2), as well as a range of ratios between the base and compound of formula II in step (2). In this instance, modifying concentrations or quantities (result effective variables) would be obvious based on routine optimization ( In re Aller), unless there is evidence to the contrary. Furthermore, the specification does not show that modification of said variables is critical to the claimed invention. The selection of reaction conditions is more optimization by more modification of routine experimentation and within one skilled in the art. Change in temperature, concentration, or both is not patentable modification in the absence of unexpected results which is different in kind and not degree. Therefore, the determination of workable feeding mass ratio would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the criticality of the claimed feeding mass ratio , the determination of the optimum or workable feeding mass ratio given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller , 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation."). Accordingly, claims 6 is rejected. A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. ( In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. Claim(s) 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Arnold (US 2017/0112182 A1, effectively filed October 23, 2015, on Applicant IDS submitted March 9, 2026)(hereinafter “Arnold”), in view of Zhang et al. ( Org. Biomol . Chem., published 2017)(hereinafter, “Zhang”). Regarding claim 7 , Arnold reports the same synthetic sequence and series of steps and reaction conditions as instant claim 1 (see Previous 35 USC § 103 rejection beginning with “R egarding claim 1 ” ) . However, Arnold does not report that the reduction is performed in the presence of a ligand and a metal catalyst in order to induce asymmetry in the hydrogenation step. Zhang reports the use of S -BINAP , or L 2 of instant claim 7, in the presence of [ Ir (COD)Cl ] 2 to hydrogenate cyclic imines with high enantioselectivities. The active Ir catalyst is prepared in situ from [ Ir (COD)Cl] 2 precursor and S - BINAP ligand. The synthetic transformation is shown below (page 3007, Table 1) with special attention to Entry 8, which uses S -BINAP (i.e. L2) to achieve 45% conversion with 88% ee to reduced product. Zhang reports that the “highly efficient and enantioselective hydrogenation of cyclic imines remains a great challenge due to the inhibitory effect from the resulting free amines with strong coordination to the central metal” but, even so, Zhang successfully demonstrates, as shown in Table 1 , Entry 8 , that in situ generation of active catalyst from [ Ir (COD)Cl] 2 precursor and S - BINAP ligand can exert enantiocontrol in order to achieve ee while m inimiz ing the inhibitory effect from the amine product of the reaction . Therefore, it would have been prima facie obvious to try at the time of the effective filing date for one of ordinary skill in the art to take the known synthetic preparation of Arnold and substitute with the asymmetric reduction conditions of Zhang to yield the reasonably predictable result of chiral L-nicotine. One of ordinary skill would find motivation in that Zhang teaches asymmetric reduction of cyclic imines is a known challenge in the field , and then Zhang successfully demonstrates the asymmetric reduction with the metal and ligand system claimed in instant claim 7. Regarding claim 8 , it would have been obvious to use a reagent for methylation in step (3) wherein the reagent for methylation is selected from formaldehyde (e.g., an aqueous formaldehyde solution), paraformaldehyde, iodomethane, and dimethyl sulfate because Arnold teaches the use of a reagent for methylation, specifically formaldehyde, at this same synthetic step (page 11, Synthesis Example 5, para 0076) CONCLUSION All claims are rejected. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT LUKE ALAN BORALSKY whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-9746 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday 7:30 am - 5:00 am . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Jeffrey H Murray can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-9023 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /L.A.B./ Examiner, Art Unit 1624 /JEFFREY H MURRAY/ Supervisory Patent Examiner, Art Unit 1624