The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of Group I, claims 1-7, in the reply filed on July 17, 2026 is acknowledged.
Claims 2, 8-13, 15-17 are canceled. Claim 14 is currently withdrawn from consideration by the examiner because it is drawn to a non-elected invention. Claims 18-28 are new and directed to the subject matter of elected Group I. Claims 1, 3-7, 18-28 are under consideration.
Priority: This application is a DIV of U.S. Application 17288619, filed April 26, 2021, now abandoned, which is a 371 of PCT/IL2019/051151, filed October 24, 2019, which claims benefit of provisional applications 62/750862, filed October 26, 2018, and 62/758722, filed November 12, 2018.
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 1, 3, 18-25 are rejected under 35 U.S.C. 103 as being unpatentable over Gonnelli et al. (2009 Biochimica et Biophysica Acta 1794: 569-576; IDS 08.21.24) in view of Katsnelson (WO 2014176309; IDS 08.21.24), and evidenced by Roberts et al. (2002 Advanced Drug Delivery Reviews 54: 459-476; IDS 08.21.24). Gonnelli et al. disclose PEG (polyethylene glycol) is a water soluble, biocompatible polymer used extensively in protein formulations and that covalently binding to proteins leads to improved pharmacological properties including among others longer half-life (p. 569). Gonnelli et al. disclose a solution comprising PEGylated alcohol dehydrogenase, where PEG is covalently linked to the alcohol dehydrogenase (at least p. 569-570, 572). Gonnelli et al. do not explicitly teach PEG is linked at the carboxy terminus of the alcohol dehydrogenase.
Katsnelson discloses a PEGylated ALDH2 (aldehyde dehydrogenase) enzyme for lowering alcohol levels (at least paragraphs 00039-00044, 00046, 00058). Katsnelson discloses modification by PEG can occur at random or predetermined positions, including methodologies known in the art (citing Roberts et al.), which disclose protein pegylation including at least at the C-terminus (at least paragraph 00051).
Roberts et al. (cited in Katsnelson above) disclose that for proteins, typical reactive amino acids for pegylation include among others the N-terminal amino group and the C-terminal carboxylic acid (at least p. 461).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the references and arrive at the claimed composition comprising a protein comprising an amino acid sequence of an alcohol dehydrogenase (ADH), wherein the carboxy terminus of said protein is bound to at least one PEG (instant claims 1, 8, 18-19, 20-25). The motivation to do so is given by the prior art. Gonnelli et al. disclose a PEGylated alcohol dehydrogenase, where it is known that PEG improves the half-life of the protein. Katsnelson discloses modification by PEG can occur at positions using methodologies known in the art (citing Roberts et al.), which disclose protein pegylation including at the C-terminus of the protein. Therefore, one of ordinary skill would have reasonable motivation to conjugate the PEG molecule at the carboxy terminus of the alcohol dehydrogenase in Gonnelli et al. because Katsnelson discloses known positions for pegylation include the C-terminus of the protein. One of ordinary skill would have a reasonable expectation of success because protein pegylation methodologies were known as disclosed in the cited prior art.
Regarding instant claims 20-21, 22-25, Gonnelli et al. disclose PEG is a water soluble, biocompatible polymer used extensively as a stabilizer in protein formulations; covalent binding to enzymes leads to improved pharmacological properties, including a better resistance to proteolytic cleavage, higher solubility in physiological media, longer plasma half-life, better immunocompatibility (p. 569).
Claims 1, 3, 4, 5-7, 18-25, 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Gonnelli et al. (2009 Biochimica et Biophysica Acta 1794: 569-576; IDS 08.21.24) in view of Katsnelson (WO 2014176309; IDS 08.21.24) and Somberg et al. (US 20090060894; IDS 08.21.24). The teachings of Gonnelli et al. and Katsnelson over instant claims 1, 3, 18-25 are noted above. As noted above, Gonnelli et al. and Katsnelson disclose a PEGylated alcohol dehydrogenase, where the PEG is conjugated at the carboxy terminus of the enzyme. Gonnelli et al. disclose that PEG is used extensively in protein formulations and that covalently binding to proteins leads to improved pharmacological properties including among others longer half-life (p. 569).
Somberg et al. disclose alcohol is metabolized by alcohol dehydrogenase and then the product aldehyde is then metabolized by aldehyde dehydrogenase (at least paragraph 0004). Somberg et al. disclose a method of moderating the buildup of alcohol in the blood of a patient, comprising administering to the patient an effective amount of alcohol dehydrogenase sufficient to reduce the blood alcohol level in the patient (at least p. 2 claim 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the references and arrive at the claimed method for lowering blood alcohol in a subject in need thereof, comprising administering to the subject a composition comprising a protein comprising an alcohol dehydrogenase bound to at least one long-acting molecule, such as a PEGylated alcohol dehydrogenase where a PEG is conjugated at the carboxy terminus of the protein, thereby lowering blood alcohol in the subject (instant claims 1, 3, 5, 27-28). The motivation to do so is given by the prior art. Gonnelli et al. disclose a PEGylated alcohol dehydrogenase, where it is known that PEG improves the half-life of the protein. Katsnelson discloses modification by PEG can occur at positions using methodologies known in the art (citing Roberts et al.), which disclose protein pegylation including at the C-terminus of the protein. Somberg et al. disclose administering alcohol dehydrogenase to lower blood alcohol levels in a patient. Therefore, one of ordinary skill would have reasonable motivation to incorporate or administer an alcohol dehydrogenase pegylated at the C-terminus as suggested in Gonnelli et al. and Katsnelson to a patient in the method of Somberg et al. for lowering blood alcohol levels in the patient. One of ordinary skill would have a reasonable expectation of success because it is disclosed alcohol dehydrogenase can be administered to subjects for lowering blood alcohol levels.
Regarding instant claim 4, Somberg et al. disclose an effective amount including 102 mg to 157 mg alcohol dehydrogenase (p. 2 example).
Regarding instant claim 7, Somberg et al. disclose alcohol intoxication is a serious problem (at least paragraph 0002) and moderating the adverse buildup of alcohol in the body following alcoholic beverage ingestion by administering alcohol dehydrogenase (at least paragraph 0005). Therefore, it would be obvious that the alcohol dehydrogenase is administered to patients in need thereof having elevated alcohol levels, including patients in need thereof having blood alcohol concentration above 0.0001% by blood volume.
Regarding instant claim 6, as noted above, Somberg et al. disclose an effective amount including 102 mg to 157 mg alcohol dehydrogenase (p. 2 example). Katsnelson also discloses a PEGylated ALDH2 (aldehyde dehydrogenase) enzyme for lowering alcohol levels (at least paragraphs 00039-00044, 00046, 00058). Katsnelson discloses therapeutic dosages of the PEGylated ALDH2 range from 0.001g per kg body weight to 5g per kg body weight (at least paragraphs 00018, 00080). It would have been obvious to arrive at the recited effective amount of 1 to 500 mg/kg body weight by routine optimization because Somberg et al. has disclosed effective amounts of alcohol dehydrogenase for lowering alcohol levels and Katsnelson also discloses similar dosage amounts for an aldehyde dehydrogenase having the same purpose of lowering alcohol levels.
Claims 1, 3, 4, 5-7, 18-25, 26, 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Gonnelli et al. (2009 Biochimica et Biophysica Acta 1794: 569-576; IDS 08.21.24) in view of Katsnelson (WO 2014176309; IDS 08.21.24), Somberg et al. (US 20090060894; IDS 08.21.24), Cabirol et al. (US 20170292141), and Codexis (2013 Codex® KRED (ketoreductase) Screening Kit, 4 pages). The teachings of Gonnelli et al., Katsnelson, Somberg over instant claims 1, 3, 4, 5-7, 18-25, 27-28 are noted above.
Regarding instant claim 26, Cabirol et al. disclose engineered ketoreductases have significant benefit, including improved enzyme properties, including among others increase enzymatic activity, increased thermostability, increased solvent stability, increased pH stability (at least paragraph 0066). Cabirol et al. disclose engineered ketoreductases having improved properties can allow use for conditions, including among others high alcohol concentration (at least paragraph 0066). Codexis also discloses engineered ketoreductases have enhanced properties, including selectivity, activity, substrate range, solvent stability, temperature stability (at least p. 1). Codexis discloses engineered ketoreductases include among others KRED-P1-A04, KRED-P1-B02 (at least p. 2). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the KRED-P1-A04 engineered ketoreductase of Codexis for the alcohol dehydrogenase that is PEGylated at the C-terminus of Gonnelli et al. and Katsnelson noted above. One of ordinary skill would have a reasonable expectation of success because it is disclosed KRED is an enzyme having the same purpose of lowering alcohol levels as alcohol dehydrogenase.
No claim is allowed.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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