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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/20/2026 has been entered.
The amendments filed on 08/05/2026 were entered in the advisory action mailed 08/19/2026. Claims 1-6, 9-11, and 13-18 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.
Claim Interpretation
Claims 1, 9, and 13: The claims are drawn to a method of treatment; the broadest reasonable interpretation depends on the patient population being treated.
Claims 1 and 13 recite preventing or treating a neurodegenerative disease or condition. Individuals in need of treatment of a neurodegenerative disease or condition are considered individuals (of any species) who are currently experiencing a neurodegenerative disease or condition. The specification defines a neurodegenerative disease or neurodegenerative condition as a neurodegenerative proteinopathy which results from increased aggregation-associated or misfolded protein-associated proteotoxicity and such neurodegenerative disorders are associated with aging (See specification pg. 6 ¶0017). Individuals in need of prevention of a neurodegenerative disease or condition is much broader, and will include everyone, as everyone is in need of prevention of unwanted diseases. Given the breadth of a neurodegenerative disease or condition includes several disorders including many associated with aging, a person does not need to be at risk of developing any specific neurodegenerative disease or condition to be considered in need of prevention of a neurodegenerative disease or condition.
Claim 9 recites preventing or treating Huntington’s disease. Individuals in need of treatment of Huntington’s disease are considered individuals (of any species) who are currently experiencing Huntington’s disease. The National Institute of Neurological Disorders and Stroke (NINDS) teaches Huntington’s disease is a genetic disease caused by the number of CAG repeats in the HTT gene. A person having fewer than 27 CAG repeats in the HTT gene is not considered at risk for the disease. People with 27-35 CAG repeats aren’t likely to develop the disease and people with 36 or more CAG repeats will likely develop the disease (See NINDS Huntington’s disease page. Sec. Genetic risk). Thus, Individual in need of prevention of Huntington’s disease are individuals with 27 or more CAG repeats in the HTT gene.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 13-18 under 35 U.S.C. 103 over Armstrong et al.
Applicants traverse the rejection of record on the grounds that Armstrong et al teaches amylase clears glycogen build-up rather than an effect on protein levels.
In response, Armstrong teaches a dose dependent uptake of Fab-amylase in myotubes (See pg. 149, lns 21-24 and Fig. 1). However, Armstrong only quantifies reduction of glycogen using one concentration of Fab-amylase (See Fig. 2). Thus, Armstrong does not suggest optimizing the amount of Fab-amylase to improve glycogen clearance.
The rejection is withdrawn.
RE: Rejection of claims 1-6 and 13-18 under 35 U.S.C. 103 over Armstrong et al in view of Pfanstiehl.
Applicants amended claim 1 to further define an effective amount of amylase or maltose. Amendments to the claims overcome the rejection of record.
The rejection is withdrawn.
RE: Rejection of claims 1-7 and 13-18 under 35 U.S.C. 103 over Armstrong et al in view of Pfanstiehl and Brewer et al.
Applicants traverse the rejection of record on the grounds that Armstrong et al and Brewer et al fail to teach the effects of amylase on protein levels. Additionally, applicants argue Armstrong et al, Pfanstiehl, and Brewer et al fail to recognize that amylase affects aggregation-associated or misfolded protein-associated proteotoxicity, transcription of chaperones and proteases, degradation of proteasome substrates, and/or protein quality under stress conditions. Therefore, there would be no motivation to optimize the amount of amylase used in order to achieve the claimed effect.
In response, the argument has been considered but is not found persuasive. Brewer et al teaches amylase has a dose dependent effect on polysaccharide levels. Therefore, it would be obvious to optimize the amount of amylase in order to decrease polysaccharide levels and inherently achieve one of the claimed effects. Though modified for a different purpose, if the end result is the same (administration of the same amount of amylase), then Armstrong et al, Pfanstiehl, and Brewer et al still properly read on the claimed method as they suggest a motivation for administering the same active agent in the same amount to the same population.
The rejection over claims 1-6 and 13-18 is maintained.
Claim 7 has been cancelled, rendering its rejection moot.
RE: Rejection of claims 1-6, 9-11 and 13-18 under 35 U.S.C. 103 over Armstrong et al in view of Pfanstiehl, Tanaka et al, and Pierzynowski.
Applicants amended claims 1 and 9 further defining an effective amount of amylase or maltose. Amendments to the claims overcome the rejection of record.
The rejection is withdrawn.
RE: Rejection of claims 1-7 and 9-18 under 35 U.S.C. 103 as being unpatentable over Armstrong et al in view of Pfanstiehl, Tanaka et al, Pierzynowski and Brewer et al.
Applicants traverse the rejection of record on the grounds that Armstrong et al and Brewer et al fail to teach the effects of amylase on protein levels. Additionally, applicants argue Armstrong et al, Pfanstiehl, and Brewer et al fail to recognize that amylase affects aggregation-associated or misfolded protein-associated proteotoxicity, transcription of chaperones and proteases, degradation of proteasome substrates, and/or protein quality under stress conditions. Therefore, there would be no motivation to optimize the amount of amylase used in order to achieve the claimed effect.
In response, the argument has been considered but is not found persuasive. Brewer et al teaches amylase has a dose dependent effect on polysaccharide levels. Therefore, it would be obvious to optimize the amount of amylase in order to decrease polysaccharide levels and inherently achieve one of the claimed effects. Though modified for a different purpose, if the end result is the same (administration of the same amount of amylase), then Armstrong et al, Pfanstiehl, and Brewer et al still properly read on the claimed method as they suggest a motivation for administering the same active agent in the same amount to the same population.
The rejection over claims 1-6, 9-11, and 13-18 is maintained.
Claims 7 and 12 have been cancelled, rendering their rejection moot.
New/Modified Rejections
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 13 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Aoki (US20180236091A1).
Aoki discloses a pharmaceutical preparation comprising 100 mg/mL of maltose (See Example 15, ¶0138). The pharmaceutical preparation is administered into the blood vessels for injection or infusion (See ¶0111).
Regarding claim 13: Aoki discloses administering a pharmaceutical preparation comprising 100 mg/mL of maltose which reads on a method for preventing a neurodegenerative disease or condition comprising administering to a subject in need thereof an effective amount of maltose.
The specification of the instant application discloses Example 8 in which Drosophila cells are treated with 1.7 mg/mL of recombinant porcine amylase or 100 mg/mL of maltose (See ¶0078 and ¶00112). Treatment with recombinant amylase resulted in reduced accumulation of poly-ubiquitinated proteins which reads on amylase preserves protein quality and similar results were obtained with maltose treatment (See ¶00112).
Given that the pharmaceutical preparation of Aoki comprises 100 mg/mL of maltose, the composition of Aoki inherently reduces accumulation of poly-ubiquitinated proteins.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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) in view of Brewer et al (Cell Metabolism, 2019).
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 or 100mg/mL of maltose (See ¶0078 and ¶00112). Treatment with recombinant amylase resulted in reduced accumulation of poly-ubiquitinated proteins which reads on amylase preserves protein quality and similar results were obtained with maltose treatment (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, in a dose dependent manner (See Fig. 5). Brewer uses various concentrations of VAL-0417 ranging from 0.025 mg/mL to 30 mg/mL, depending on whether tests are performed in vitro or in vivo (See Secs. In vitro degradation assays, In vivo mouse studies and Fig. 5) Thus, the dosage of 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 alpha amylase, and Brewer et al teaches increasing the concentration of amylase results in decreased polysaccharide levels, it would have been prima facie obvious to optimize the concentration of alpha amylase administered to the subject, and reach a concentration which inherently 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 through routine experimentation. One would have been motivated to optimize the concentration of alpha amylase in the method of Armstrong et al because Brewer et al teaches increasing amylase decreases polysaccharide levels. 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) and Brewer et al (Cell Metabolism, 2019).
The teachings of Armstrong et al and Brewer et al are set forth above.
Armstrong et al and Brewer et al render 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.
Additionally, 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, in a dose dependent manner (See Fig. 5). Brewer uses various concentrations of VAL-0417 ranging from 0.025 mg/mL to 30 mg/mL, depending on whether tests are performed in vitro or in vivo (See Secs. In vitro degradation assays, In vivo mouse studies and 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 alpha amylase, and Brewer et al teaches increasing the concentration of amylase results in decreased polysaccharide levels, it would have been prima facie obvious to optimize the concentration of alpha amylase administered to the subject, and reach a concentration which inherently 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 through routine experimentation. One would have been motivated to optimize the concentration of alpha amylase in the method of Armstrong et al because Brewer et al teaches increasing amylase decreases polysaccharide levels. 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 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 1-6, 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), Brewer et al (Cell Metabolism, 2019) and Pierzynowski (US20150297544A1).
The teachings of Armstrong et al, Pfanstiehl, and Brewer et al are set forth above.
Armstrong et al and Brewer et al render claims 13-18 obvious.
Armstrong et al, Pfanstiehl, and Brewer et al 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.
Additionally, 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, in a dose dependent manner (See Fig. 5). Brewer uses various concentrations of VAL-0417 ranging from 0.025 mg/mL to 30 mg/mL, depending on whether tests are performed in vitro or in vivo (See Secs. In vitro degradation assays, In vivo mouse studies and 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 alpha amylase, and Brewer et al teaches increasing the concentration of amylase results in decreased polysaccharide levels, it would have been prima facie obvious to optimize the concentration of alpha amylase administered to the subject, and reach a concentration which inherently 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 through routine experimentation. One would have been motivated to optimize the concentration of alpha amylase in the method of Armstrong et al because Brewer et al teaches increasing amylase decreases polysaccharide levels. 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 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.
Conclusion
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.
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/MARISOL ANN O'NEILL/ Examiner, Art Unit 1633
/ALLISON M FOX/ Primary Examiner, Art Unit 1633
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