The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 5, 2026 has been entered.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 1-14 are canceled. Claims 15-19, 20-34 are under consideration.
Priority: This application claims benefit to the earliest provisional application 61/028141, filed February 12, 2008.
Objections and Rejections
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 15-19, 21-22, 33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kaneski et al. (US 7851143; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited). Kaneski et al. disclose treating patients having Fabry disease mutation G328A by administering 1-deoxygalactonojirimycin (DGJ) in Example 2 (col. 24). The patient was identified as possibly being responsive to DGJ based on a patient derived T cell assay in which DGJ was shown in increase the alpha-galactosidase A activity in cultured patient derived T cells. Kaneski et al. disclose that DGJ refers to both the free base and any salt form; the hydrochloride salt of DGJ is known as migalastat hydrochloride (col. 7 lines 39-53). Kaneski et al. other alpha-galactosidase A mutations that cause Fabry disease are known (at least col. 2 lines 38-56).
Shabbeer et al. disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (at least p. 297). Shabbeer et al. disclose various missense mutations leading to misfolding and disruption of the alpha-galactosidase A protein, including among others N34K, D264Y, V269M, Q321R, E338K, etc. (Tables 1, 3) and the G328A of Kaneski et al. (Table 1). Shabbeer et al. also disclose pharmaceutical chaperones, including deoxygalactonojirimycin, have been used to rescue alpha-galactosidase A mutants that are misfolded and degraded (at least p. 298).
It would have been obvious to one of ordinary skill in the art to combine the references and arrive at the claimed method comprising treating a patient diagnosed with Fabry disease, comprising administering to the patient in need thereof a therapeutically effective dose of DGJ or a salt thereof, wherein the patient is identified as having a mutation in alpha-galactosidase A, relative to a human alpha-galactosidase A, wherein the mutation is selected from among D264Y (instant claims 15, 21). The motivation to do so is given by the prior art. Kaneski et al. disclose treating patients having Fabry disease mutations by administering DGJ. Shabbeer et al. identify various missense mutations leading to misfolding and disruption of the alpha-galactosidase A protein, including mutations N34K, D264Y, V269M, Q321R, E338K, etc. Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is D264Y as disclosed in Shabbeer et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects and in rescuing misfolded or disrupted alpha-galactosidase A protein, where identified and known mutations leading to misfolded alpha-galactosidase A protein include D264Y.
Regarding instant claims 16, 19, Kaneski et al. disclose patients with Fabry disease can be female or male (at least col. 2 lines 12-13).
Regarding instant claims 17-18, Kaneski et al. disclose that DGJ refers to both the free base and any salt form; the hydrochloride salt of DGJ is known as migalastat hydrochloride (col. 7 lines 39-53).
Regarding instant claims 15, 22, Shabbeer et al. disclose G271S is an alpha-galactosidase A mutation causing Fabry disease (at least p. 297, 299, also Table 1, 3). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is G271S as disclosed in Shabbeer et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include G271S.
Regarding instant claims 15, 33, Shabbeer et al. disclose S201Y is an alpha-galactosidase A mutation causing Fabry disease (at least p. 297, 299, also Table 1, 3). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is S201Y as disclosed in Shabbeer et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include S201Y.
Claims 15-19, 20, 21-22, 25, 33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kaneski et al. (US 7851143; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited) and/or Shabbeer II (2002 Molecular Genetics and Metabolism 76: 23-30). The teachings of Kaneski et al. and Shabbeer et al. over at least instant claims 15, 21-22, 33 are noted above. Shabbeer II, like Shabbeer et al., also disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (Shabbeer II p. 23).
Regarding instant claims 15, 20, Shabbeer II discloses A288P is an alpha-galactosidase A mutation causing Fabry disease (at least p. 23, 25, also Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is A288P as disclosed in Shabbeer II. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include A288P.
Regarding instant claims 15, 25, Shabbeer II discloses I303N is an alpha-galactosidase A mutation causing Fabry disease (at least p. 23, 25, also Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is I303N as disclosed in Shabbeer II. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include I303N.
Claims 15-19, 21-22, 27, 33, 34 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kaneski et al. (US 7851143; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited) and/or Shabbeer III (2005 Human Mutation 25:299-305). The teachings of Kaneski et al. and Shabbeer et al. over at least instant claims 15, 21-22, 33 are noted above. Shabbeer III, like Shabbeer et al., also disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (Shabbeer III p. 299, 301).
Regarding instant claims 15, 27, Shabbeer III discloses L300F is an alpha-galactosidase A mutation causing Fabry disease (at least p. 303, Table 2). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is L300F as disclosed in Shabbeer III. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include L300F.
Regarding instant claims 15, 34, Shabbeer III discloses a protein effect at position S345 (at least p. 302, Table 2). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation is at position S345 as disclosed in Shabbeer III, including a mutation S345P. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include mutations at position S345.
Claims 15-19, 21-22, 23-24, 28-29, 31-32, 33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kaneski et al. (US 7851143; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited) and/or Garman et al. (2002 Molecular Genetics and Metabolism 77: 3-11). The teachings of Kaneski et al. and Shabbeer et al. over at least instant claims 15, 21-22, 33 are noted above. Garman et al., like Shabbeer et al., also disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (Garman et al. p. 3-4, Table 1).
Regarding instant claims 15, 23, Garman et al. disclose G35R is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is G35R as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include G35R.
Regarding instant claims 15, 24, Garman et al. disclose I242N is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is I242N as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include I242N.
Regarding instant claims 15, 28, Garman et al. disclose N224S is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is N224S as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include N224S.
Regarding instant claims 15, 29, Garman et al. disclose P259L is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is P259L as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include P259L.
Regarding instant claims 15, 31, Garman et al. disclose Q280H is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is Q280H as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include Q280H.
Regarding instant claims 15, 32, Garman et al. disclose R301P is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is R301P as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include R301P.
Claims 15-19, 21-22, 26, 30, 33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kaneski et al. (US 7851143; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited) and/or Germain et al. (2002 Molecular Medicine 8(6): 306-312). The teachings of Kaneski et al. and Shabbeer et al. over at least instant claims 15, 21-22, 33 are noted above. Germain et al., like Shabbeer et al., also disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (Germain et al. p. 306, 308, also Table 2).
Regarding instant claims 15, 26, Germain et al. disclose L243F is an alpha-galactosidase A mutation causing Fabry disease (at least p. 306, 308, also Table 2). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is L243F as disclosed in Germain et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include L243F.
Regarding instant claims 15, 30, Germain et al. disclose P409S is an alpha-galactosidase A mutation causing Fabry disease (at least p. 306, 308, also Table 2). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Kaneski et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is P409S as disclosed in Germain et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include P409S.
Claims 15-19, 21-22, 33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Fan et al. (2007 FEBS Journal 274(19): 4962-4971; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited) and Hollak et al. (2007 Expert Opin Ther Targets 11(6): 821-833; previously cited). Fan et al. disclose 1-deoxygalactonojirimycin (DGJ) is one of the most potent inhibitors of alpha-galactosidase A and has been shown to be the most effective active-site-specific chaperone at increasing residual enzyme activity in cultured fibroblasts and lymphoblasts established from Fabry patients with a variety of missense mutations (at least p. 4962). Fan et al. disclose oral administration of DGJ to transgenic mice expressing a human R301A alpha-galactosidase A yielded higher alpha-galactosidase A activity in major tissues (at least p. 4962). Fan et al. disclose DGJ is expected to be highly effective for patients who have missense mutations that lead to misfolding of the mutant protein (at least p. 4969). Fan et al. disclose that DGJ could be of therapeutic benefit to Fabry patients with a variety of missense mutations (at least p. 4962, 4969). Fan et al. do not teach other missense mutations of Fabry disease.
Shabbeer et al. disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (at least p. 297). Shabbeer et al. disclose various missense mutations leading to misfolding and disruption of the alpha-galactosidase A protein, including among others N34K, D264Y, V269M, Q321R, E338K, etc. (Tables 1, 3). Shabbeer et al. also disclose pharmaceutical chaperones, including deoxygalactonojirimycin, have been used to rescue alpha-galactosidase A mutants that are misfolded and degraded (at least p. 298).
Hollak et al. also disclose a chemical chaperone may be efficacious for treating Fabry disease, including deoxygalactonojirimycin (migalastat hydrochloride) (at least p. 827-828).
It would have been obvious to one of ordinary skill in the art to combine the references and arrive at the claimed method comprising treating a patient diagnosed with Fabry disease, comprising administering to the patient in need thereof a therapeutically effective dose of DGJ or a salt thereof, wherein the patient is identified as having a mutation in alpha-galactosidase A, relative to a human alpha-galactosidase A, wherein the mutation is selected from among D264Y (instant claims 15, 21). The motivation to do so is given by the prior art. Fan et al. disclose the therapeutic efficacy of DGJ in subjects having a missense mutation leading to a misfold or mutant form of alpha-galactosidase A. Shabbeer et al. identify various missense mutations leading to misfolding and disruption of the alpha-galactosidase A protein, including mutations N34K, D264Y, V269M, Q321R, E338K, etc. Hollak et al. also disclose a chemical chaperone may be efficacious for treating Fabry disease, including deoxygalactonojirimycin (migalastat hydrochloride). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is D264Y as disclosed in Shabbeer et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects and in rescuing misfolded or disrupted alpha-galactosidase A protein, where identified and known mutations leading to misfolded alpha-galactosidase A protein include D264Y.
Regarding instant claims 16, 19, Hollak et al. disclose Fabry disease may manifest in males and females (at least p. 821-822).
Regarding instant claims 17-18, Hollak et al. disclose DGJ is also migalastat hydrochloride (p. 828).
Regarding instant claims 15, 22, Shabbeer et al. disclose G271S is an alpha-galactosidase A mutation causing Fabry disease (at least p. 297, 299, also Table 1, 3). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is G271S as disclosed in Shabbeer et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include G271S.
Regarding instant claims 15, 33, Shabbeer et al. disclose S201Y is an alpha-galactosidase A mutation causing Fabry disease (at least p. 297, 299, also Table 1, 3). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is S201Y as disclosed in Shabbeer et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include S201Y.
Claims 15-19, 20, 21-22, 25, 33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Fan et al. (2007 FEBS Journal 274(19): 4962-4971; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited) and/or Shabbeer II (2002 Molecular Genetics and Metabolism 76: 23-30), and Hollak et al. (2007 Expert Opin Ther Targets 11(6): 821-833; previously cited). The teachings of Fan et al., Shabbeer et al., and Hollak et al. over at least instant claims 15, 21-22, 33 are noted above. Shabbeer II, like Shabbeer et al., also disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (Shabbeer II p. 23).
Regarding instant claims 15, 20, Shabbeer II discloses A288P is an alpha-galactosidase A mutation causing Fabry disease (at least p. 23, 25, also Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is A288P as disclosed in Shabbeer II. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include A288P.
Regarding instant claims 15, 25, Shabbeer II discloses I303N is an alpha-galactosidase A mutation causing Fabry disease (at least p. 23, 25, also Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is I303N as disclosed in Shabbeer II. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include I303N.
Claims 15-19, 21-22, 27, 33, 34 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Fan et al. (2007 FEBS Journal 274(19): 4962-4971; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited) and/or Shabbeer III (2005 Human Mutation 25:299-305), and Hollak et al. (2007 Expert Opin Ther Targets 11(6): 821-833; previously cited). The teachings of Fan et al., Shabbeer et al., and Hollak et al. over at least instant claims 15, 21-22, 33 are noted above. Shabbeer III, like Shabbeer et al., also disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (Shabbeer III p. 299, 301).
Regarding instant claims 15, 27, Shabbeer III discloses L300F is an alpha-galactosidase A mutation causing Fabry disease (at least p. 303, Table 2). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is L300F as disclosed in Shabbeer III. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include L300F.
Regarding instant claims 15, 34, Shabbeer III discloses a protein effect at position S345 (at least p. 302, Table 2). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation is at position S345 as disclosed in Shabbeer III, including a mutation S345P. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include mutations at position S345.
Claims 15-19, 21-22, 23-24, 28-29, 31-32, 33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Fan et al. (2007 FEBS Journal 274(19): 4962-4971; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited) and/or Garman et al. (2002 Molecular Genetics and Metabolism 77: 3-11), and Hollak et al. (2007 Expert Opin Ther Targets 11(6): 821-833; previously cited). The teachings of Fan et al., Shabbeer et al., and Hollak et al. over at least instant claims 15, 21-22, 33 are noted above. Garman et al., like Shabbeer et al., also disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (Garman et al. p. 3-4, Table 1).
Regarding instant claims 15, 23, Garman et al. disclose G35R is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is G35R as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include G35R.
Regarding instant claims 15, 24, Garman et al. disclose I242N is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is I242N as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include I242N.
Regarding instant claims 15, 28, Garman et al. disclose N224S is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is N224S as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include N224S.
Regarding instant claims 15, 29, Garman et al. disclose P259L is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is P259L as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include P259L.
Regarding instant claims 15, 31, Garman et al. disclose Q280H is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is Q280H as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include Q280H.
Regarding instant claims 15, 32, Garman et al. disclose R301P is an alpha-galactosidase A mutation causing Fabry disease (at least p. 4, Table 1). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is R301P as disclosed in Garman et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include R301P.
Claims 15-19, 21-22, 26, 30, 33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Fan et al. (2007 FEBS Journal 274(19): 4962-4971; previously cited) in view of Shabbeer et al. (2006 Human Genomics 2(5): 297-309; previously cited) and/or Germain et al. (2002 Molecular Medicine 8(6): 306-312), and Hollak et al. (2007 Expert Opin Ther Targets 11(6): 821-833; previously cited). The teachings of Fan et al., Shabbeer et al., and Hollak et al. over at least instant claims 15, 21-22, 33 are noted above. Germain et al., like Shabbeer et al., also disclose and identify missense mutations of human alpha-galactosidase A of Fabry disease (Germain et al. p. 306, 308, also Table 2).
Regarding instant claims 15, 26, Germain et al. disclose L243F is an alpha-galactosidase A mutation causing Fabry disease (at least p. 306, 308, also Table 2). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is L243F as disclosed in Germain et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include L243F.
Regarding instant claims 15, 30, Germain et al. disclose P409S is an alpha-galactosidase A mutation causing Fabry disease (at least p. 306, 308, also Table 2). Therefore, one of ordinary skill would have reasonable expectation to administer a therapeutically effective dose of the DGJ disclosed in Fan et al./Hollak et al. in a patient having Fabry disease and identified as having a mutation in alpha-galactosidase A, where the mutation identified is P409S as disclosed in Germain et al. One of ordinary skill would have a reasonable expectation of success because the prior art discloses that DGJ has therapeutic efficacy in treating Fabry disease in subjects, where identified and known alpha-galactosidase A mutations causing Fabry disease include P409S.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining the 103 rejections are noted above.
The prior art disclose DGJ is expected to be highly effective for patients who have missense mutations that lead to misfolding of the mutant protein (Kaneski et al.; Fan et al.). Shabbeer et al. disclose various missense mutations leading to misfolding and disruption of the alpha-galactosidase A protein, including among others N34K, D264Y, V269M, Q321R, E338K, etc. (at least Table 3). Shabbeer et al. also disclose pharmaceutical chaperones, including deoxygalactonojirimycin, have been used to rescue alpha-galactosidase A mutants that are misfolded and degraded (at least p. 298).
Therefore, it would have been obvious to one of ordinary skill in the art to combine the references and arrive at the claimed method comprising treating a patient diagnosed with Fabry disease, comprising administering to the patient in need thereof a therapeutically effective dose of DGJ or a salt thereof, wherein the patient is identified as having a mutation in alpha-galactosidase A, relative to a human alpha-galactosidase A, wherein the mutation is selected from among D264Y (instant claim 15). Additionally, the newly cited references of Shabbeer II, Shabbeer III, Garman et al., and Germain et al. disclose other known alpha-galactosidase A mutations that cause Fabry disease and which are recited in new claims 20-34. See the 103 rejections above.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 15-19, 20-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 8592362 (‘362). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ‘362 patent claims are drawn to a method for treating a patient diagnosed with Fabry disease comprising administering to the patient a therapeutically effective dose of DGJ, wherein the patient is identified as having a mutant alpha-galactosidase A. The mutations recited in instant claim 15 and its dependent claims are the same as the mutations identified and recited in the ‘362 patent claim 1.
Regarding instant claims 16, 19, the ‘362 patent claim 2 recites the patient is female. Therefore, it would be further obvious that patients encompassed by the ‘362 patent claim 1 encompasses male patients.
Regarding instant claims 17-18, the ‘362 patent claims 3-4 recite the DGJ is DGJ hydrochloride.
Reply: Applicants’ remarks have been considered but they are not persuasive. Applicants assert that the amended claims are narrower in scope than the ‘362 patent.
Applicants’ remarks are not persuasive. The instant claims and the ‘362 patent claims are still drawn to a method for treating a patient diagnosed with Fabry disease comprising administering to the patient a therapeutically effective dose of DGJ, wherein the patient is identified as having a mutant alpha-galactosidase A, and where the mutations recited in instant claim 15 are also among the mutations identified and recited in the ‘362 patent claim 1.
Claims 15-19, 20-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-10 of U.S. Patent No. 9095584 (‘584) in view of Shabbeer (supra) and Wu et al. (2008 Molecular Genetics and Metabolism 93(2): S43-S44, abstract 113, available online January 14, 2008; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ‘584 patent claims are drawn to a method for treating a patient diagnosed with Fabry disease comprising administering to the patient a therapeutically effective dose of DGJ, wherein the patient is identified as having a mutant alpha-galactosidase A. The ‘584 patent claims differ from the instant claims by not explicitly reciting specific mutations identified. However, the ‘584 specification discloses alpha-galactosidase A mutations of Fabry disease, where the alpha-galactosidase A mutations disclosed in the ‘584 specification are the same mutations recited in the instant claim 15 and its dependent claims. Wu et al. disclose identifying DGJ responsive mutations by an assay utilizing HEK-293 cells having the mutation in the presence of absence of DGJ or a salt thereof (abstract 113, p. S44). Therefore, it would have been obvious to arrive at the recited alpha-galactosidase A mutations by an assay utilizing HEK-293 cells recited in the method of the ‘584 patent claims. One of ordinary skill would have a reasonable expectation of success because Wu et al. disclose assay validation carried out on Fabry missense mutations and the results obtained in HEK-293 cells were similar to those obtained from both Fabry patient-derived lymphoid cell lines and primary T-cell cultures (abstract 113, p. S44) and alpha-galactosidase A mutations, including the alpha-galactosidase A mutations recited in the instant claims, have been identified and are known, and are encompassed by the ‘584 patent claims.
Regarding instant claims 16, 19, the ‘584 patent claim 10 recites the patient is female. Therefore, it would be further obvious that patients encompassed by the ‘584 patent claim 6 encompasses male patients.
Regarding instant claims 17-18, the ‘584 patent claims 8-9 recite the DGJ is DGJ hydrochloride.
Reply: Applicants’ remarks have been considered but they are not persuasive.
As noted above, the ‘584 patent claims are drawn to a method for treating a patient diagnosed with Fabry disease comprising administering to the patient a therapeutically effective dose of DGJ, wherein the patient is identified as having a mutant alpha-galactosidase A.
The ‘584 specification discloses alpha-galactosidase A mutations of Fabry disease, where the alpha-galactosidase A mutations disclosed in the ‘584 specification are the same mutations recited in the instant claim 15 and its dependent claims.
Therefore, the alpha-galactosidase A mutations encompassed by the ‘584 patent claims reasonably include identified and known alpha-galactosidase A mutations as disclosed in the ‘584 specification, including the alpha-galactosidase A mutations recited in the instant claims.
No claim is allowed.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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