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 .
Applicants’ response on 11/26/2025 has been received and entered. Claims 1-7 and 9-18 are pending, all of which have been considered on the merits.
Election/Restrictions
Applicants previously elected the species of ‘wherein the method comprises administering amylase’. All claims will be examined in so far as they require administration of at least amylase.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1, 2, 5, and 6 under 35 U.S.C. 102 over Pierzynowski (US20150297544A1).
Applicants’ amendments to the claims requiring administering amylase and maltose overcomes the rejection of record. The rejection is withdrawn.
RE: Rejection of claims 1-6 are rejected under 35 U.S.C. 102 over Armstrong et al (WO2019178532A1).
Applicants’ amendments to the claims requiring administering amylase and maltose overcomes the rejection of record. The rejection is withdrawn.
RE: Rejection of claims 1-7 under 35 U.S.C. 103 over Armstrong et al (WO2019178532A1).
Applicants’ amendments to the claims requiring administering amylase and maltose overcomes the rejection of record. The rejection is withdrawn because of claim amendments.
For completeness, applicant’s argument about Armstrong not rendering obvious administration of amylase in an amount effective to reduce aggregation-associated or misfolded protein-associated proteotoxicity, induce transcription of chaperones and proteases, promote degradation of proteasome substrates, and/or preserve protein quality under stress conditions (relevant to original claim 7, and new claims 13-18) will be briefly addressed:
Applicants asserts it would not have been obvious to optimize the concentration of alpha amylase administrated to the subject because Armstrong does not recognize that the concentration of alpha amylase affects, e.g., protein quality. This is not found persuasive because it would have been obvious to optimize the concentration of alpha amylase based on its effect on polyglucosan accumulation. Though modified for a different purpose, if the end result is the same (administration of the same amount of amylase), then Armstrong et al still properly reads on the claimed method as it teaches administering the same active agent in the same amount to the same patient population.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Armstrong et al (WO2019178532A1).
Armstrong et al discloses a method for treating Alzheimer’s disease and Lafora disease comprising administering a therapeutically effective amount of a chimeric polypeptide comprising an alpha-amylase polypeptide and an internalizing moiety (claim 66 and pg. 164, ln 13 - pg. 165 ln 23). In some embodiments the nucleic acids encoding alpha-amylase are administered using viral and non-viral based gene transfer methods (pg. 127, ln 28 – pg. 128, ln 4). Armstrong further discloses a method of treating a Lafora disease mutant mouse model by administering Fab-Alpha-Amylase protein (See pg. 150, lns 17-30). In one example, 10 mg/mL of Fab-Alpha-Amylase is injected intramuscularly into the mice (See Pg. 154, lns 17-22). In other embodiments, the Fab-Alpha-Amylase is injected intravenously (See Pg. 133, lns 10-15).
Regarding claim 13: Armstrong et al discloses a method for treating Alzheimer’s disease and Lafora disease (read on neurodegenerative diseases). The method comprises administering a therapeutically effective amount of an alpha-amylase peptide fused to an internalizing moiety. Thus, Armstrong et al discloses a method of treating a neurodegenerative disease comprising administering to a subject an effective amount of amylase. In some examples, the effective amount is 10 mg/mL.
Armstrong et al does not disclose the effective amount of amylase reduces aggregation associated or misfolded protein-associated proteotoxicity, induces transcription of chaperones and proteases, promotes degradation of proteasome substrates, or preserves protein quality under stress conditions in a subject.
The specification of the instant application discloses Example 8 in which Drosophila cells are treated with 1.7 mg/mL of recombinant porcine amylase (See ¶0078 and ¶00112). Treatment with recombinant amylase resulted in reduced accumulation of poly-ubiquitinated proteins which reads on amylase preserves protein quality (See ¶00112).
Given that Armstrong et al discloses a method of treating a neurodegenerative disorder by administering an 10mg/mL alpha-amylase intramuscularly and Armstrong further discloses the alpha amylase can be administered using a vector comprising a nucleic acid molecule, it would have been prima facie obvious to optimize the concentration of alpha amylase administered to the subject, and reach a concentration which inherently preserves protein quality, based on form and route of administration. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05)).
Regarding claim 14: Following the discussion of claim 13 above, Armstrong discloses examples in which a Fab-Alpha-Amylase protein is used for treatment of Lafora disease in mouse models which reads on the amylase is administered in the form of an isolated amylase protein.
Regarding claims 15 and 16: Following the discussion of claim 13 above, Armstrong et al discloses in some embodiments the nucleic acid encoding the alpha amylase is administered using viral based gene transfer methods which reads on the amylase is administered as an amylase encoding nucleic acid molecule and the nucleic acid molecule is inserted in a viral vector.
Regarding claims 17 and 18: Following the discussion of claim 13 above, Armstrong et al discloses a method of treating Alzheimer’s disease which reads on a neurodegenerative proteinopathy.
Claims 1-6 and 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Armstrong et al (WO2019178532A1) in view of Pfanstiehl (Maltose Page, 2018).
The teachings of Armstrong et al are set forth above.
Armstrong et al renders claims 13-18 obvious.
Regarding claim 1: Armstrong et al discloses a method for treating Alzheimer’s disease and Lafora disease (read on neurodegenerative diseases). The method comprises administering a therapeutically effective amount of an alpha-amylase peptide fused to an internalizing moiety which can be a Fab. The Fab-amylase of Armstrong et al can be administered intravenously. Thus, Armstrong et al discloses a method of treating a neurodegenerative disease comprising administering to a subject an effective amount of amylase.
Armstrong et al does not disclose a treatment method comprising administering maltose.
Pfanstiehl teaches maltose is a disaccharide that can be used as an excipient for protein stabilization and is commonly used to stabilize intravenous immunoglobulin infusions (See Description).
Given that Armstrong et al discloses a treatment method comprising administering a Fab-amylase fusion protein and Pfanstiehl teaches maltose can be used to stabilize proteins and immunoglobulins, it would have been prima facie obvious to further administer an effective amount of maltose to stabilize the Fab-amylase composition of Armstrong et al in the treatment method of Armstrong et al. One would have been motivated to administer maltose in the treatment method of Armstrong et al in order to stabilize the Fab-amylase. There is a reasonable expectation of success because Pfanstiehl teaches maltose is commonly used to stabilize proteins and immunoglobulins used in IV infusions and the Fab-amylase of Armstrong can be administered intravenously.
Regarding claim 2: Following the discussion of claim 1 above, Armstrong discloses examples in which a Fab-Alpha-Amylase protein is used for treatment of Lafora disease in mouse models which reads on the amylase is administered in the form of an isolated amylase protein.
Regarding claims 3 and 4: Following the discussion of claim 1 above, Armstrong et al discloses in some embodiments the nucleic acid encoding the alpha amylase is administered using viral based gene transfer methods which reads on the amylase is administered as an amylase encoding nucleic acid molecule and the nucleic acid molecule is inserted in a viral vector.
Regarding claims 5 and 6: Following the discussion of claim 1 above, Armstrong et al discloses a method of treating Alzheimer’s disease which reads on a neurodegenerative proteinopathy.
Claims 1-7 and 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Armstrong et al (WO2019178532A1) in view of Pfanstiehl (Maltose Page, 2018) and Brewer et al (Cell Metabolism, 2019).
The teachings of Armstrong et al and Pfanstiehl are set forth above.
Armstrong et al renders claims 13-18 obvious.
Armstrong et al and Pfanstiehl render claims 1-6 and 13-18 obvious.
Regarding claims 7 and 13: Following the discussion of claim 1 above, Armstrong et al discloses a method of treating a neurodegenerative disorder comprising administering an effective amount of an alpha amylase peptide. In some examples, the effective amount is 10 mg/mL
Armstrong et al does not disclose the effective amount of amylase reduces aggregation associated or misfolded protein-associated proteotoxicity, induces transcription of chaperones and proteases, promotes degradation of proteasome substrates, or preserves protein quality under stress conditions in a subject.
The specification of the instant application discloses Example 8 in which Drosophila cells are treated with 1.7 mg/mL of recombinant porcine amylase (See ¶0078 and ¶00112). Treatment with recombinant amylase resulted in reduced accumulation of poly-ubiquitinated proteins which reads on amylase preserves protein quality (See ¶00112).
Brewer et al, a publication comprising the authors of Armstrong et al, teaches VAL-0417, a Fab-amylase fusion protein (See abstract). Brewer et al further teaches increasing the concentration of VAL-0417 results in decreased polysaccharide levels in cultured cells (See Fig. 5). Thus, the Fab-amylase fusion protein is a result effective variable.
Given that Armstrong et al discloses a method of treating a neurodegenerative disorder by administering an 10mg/mL alpha-amylase intramuscularly and Armstrong further discloses the alpha amylase can be administered using a vector comprising a nucleic acid molecule, it would have been prima facie obvious to optimize the concentration of alpha amylase administered to the subject, and reach a concentration which inherently preserves protein quality, based on form and route of administration. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05)).
Regarding claim 14: Following the discussion of claim 13 above, Armstrong discloses examples in which a Fab-Alpha-Amylase protein is used for treatment of Lafora disease in mouse models which reads on the amylase is administered in the form of an isolated amylase protein.
Regarding claims 15 and 16: Following the discussion of claim 13 above, Armstrong et al discloses in some embodiments the nucleic acid encoding the alpha amylase is administered using viral based gene transfer methods which reads on the amylase is administered as an amylase encoding nucleic acid molecule and the nucleic acid molecule is inserted in a viral vector.
Regarding claims 17 and 18: Following the discussion of claim 13 above, Armstrong et al discloses a method of treating Alzheimer’s disease which reads on a neurodegenerative proteinopathy.
Claims 1-6, 9-11 and 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Armstrong et al (WO2019178532A1) in view of Pfanstiehl (Maltose Page, 2018), Tanaka et al (Nature Medicine, 2004), and Pierzynowski (US20150297544A1).
The teachings of Armstrong et al and Pfanstiehl are set forth above.
Armstrong et al renders claims 13-18 obvious.
Armstrong et al and Pfanstiehl render claims 1-6 and 13-18 obvious.
Regarding claim 9: Armstrong et al discloses a method for treating Alzheimer’s disease and Lafora disease (read on neurodegenerative diseases). The method comprises administering a therapeutically effective amount of an alpha-amylase peptide fused to an internalizing moiety which can be a Fab. The Fab-amylase of Armstrong et al can be administered intravenously. Thus, Armstrong et al discloses a method of treating a neurodegenerative disease comprising administering to a subject an effective amount of amylase.
Armstrong et al does not disclose a treatment method comprising administering maltose.
Tanaka et al teaches Huntington’s disease is a polyglutamine disease and inhibition of polyglutamine-induced protein aggregation can provide treatment options for Huntington’s disease (See abstract). Tanaka et al further teaches various disaccharides reduce polyglutamine aggregates and increase survival in cellular models of Huntington’s disease (See abstract and Sec. Inhibitory effects of saccharides in vitro).
Pfanstiehl discloses maltose is a disaccharide.
Pierzynowski teaches amylase is an enzyme that hydrolyzes polysaccharides yielding maltose (See ¶0012).
Given that Armstrong discloses an amylase for treating neurodegenerative disorders and Tanaka discloses disaccharides reduce aggregates and increase survival in cellular models of Huntington’s disease, it would have been prima facie obvious to use the Fab-amylase of Armstrong et al as a treatment method for Huntington’s disease. One would have been motivated to use the Fab-amylase of Armstrong et al to treat Huntington’s disease because amylase hydrolyzes polysaccharides yielding maltose, a disaccharide, and disaccharides can reduce polyglutamine aggregates in Huntington’s disease. There is a reasonable expectation of success because Tanaka discloses disaccharides reduce polyglutamine aggregates and amylase hydrolyzes polysaccharides to produce the disaccharide maltose.
Regarding claim 10: Following the discussion of claim 9 above, Armstrong discloses examples in which a Fab-Alpha-Amylase protein is used for treatment of Lafora disease in mouse models which reads on the amylase is administered in the form of an isolated amylase protein.
Regarding claim 11: following the discussion of claim 9 above, Armstrong et al discloses in some embodiments the nucleic acid encoding the alpha amylase is administered using viral based gene transfer methods which reads on the amylase is administered as an amylase encoding nucleic acid molecule.
Claims 1-7 and 9-18 are rejected under 35 U.S.C. 103 as being unpatentable over Armstrong et al (WO2019178532A1) in view of Pfanstiehl (Maltose Page, 2018), Tanaka et al (Nature Medicine, 2004), Pierzynowski (US20150297544A1) and Brewer et al (Cell Metabolism, 2019).
The teachings of Armstrong et al, Pfanstiehl, Tanaka et al, and Pierzynowski are set forth above.
Armstrong et al renders claims 13-18 obvious.
Armstrong et al and Pfanstiehl render claims 1-6 and 13-18 obvious.
Armstrong et al, Pfanstiehl, and Brewer et al render claims 1-7 and 13-18 obvious.
Armstrong et al, Pfanstiehl, Tanaka et al, and Pierzynowski et al render claims 1-6 and 9-11 and 13-18 obvious.
Regarding claim 12: Following the discussion of claim 9 above, Armstrong et al in view of Pfanstiehl, Tanaka et al, and Pierzynowski teach a method of treating Huntington’s disease comprising administering a Fab-amylase.
Armstrong et al, Pfanstiehl, Tanaka et al, and Pierzynowski do not teach the effective amount of amylase reduces aggregation associated or misfolded protein-associated proteotoxicity, induces transcription of chaperones and proteases, promotes degradation of proteasome substrates, or preserves protein quality under stress conditions in a subject.
The specification of the instant application discloses Example 8 in which Drosophila cells are treated with 1.7 mg/mL of recombinant porcine amylase (See ¶0078 and ¶00112). Treatment with recombinant amylase resulted in reduced accumulation of poly-ubiquitinated proteins which reads on amylase preserves protein quality (See ¶00112).
Brewer et al, a publication comprising the authors of Armstrong et al, teaches VAL-0417, a Fab-amylase fusion protein (See abstract). Brewer et al further teaches increasing the concentration of VAL-0417 results in decreased polysaccharide levels in cultured cells (See Fig. 5). Thus, the Fab-amylase fusion protein is a result effective variable.
Given that Armstrong et al discloses a method of treating a neurodegenerative disorder by administering an 10mg/mL alpha-amylase intramuscularly and Armstrong further discloses the alpha amylase can be administered using a vector comprising a nucleic acid molecule, it would have been prima facie obvious to optimize the concentration of alpha amylase administered to the subject, and reach a concentration which inherently preserves protein quality, based on form and route of administration. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05)).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633