Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Claims 20-47 are pending.
Response to Amendment
Applicant did not amend any claim.
Priority
The later-filed application must be an application for a patent for an invention
which is also disclosed in the prior application (the parent or original nonprovisional
application or provisional application). The disclosure of the invention in the parent
application and in the later-filed application must be sufficient to comply with the
requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112,
except for the best mode requirement. See Transco Products, Inc. v. Performance
Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 61/238113, fails to
provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or
pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Independent claims 20, 29, and 36 recite the limitation “wherein the weight of the human subject is calculated using the human subject's height if the human subject has a BMI > 30”. Provisional application 61/238,113 filed on 08/28/2009 does not disclose this limitation. However, this limitation is disclosed in Application 12/870,790 filed on 08/28/2010. Claims 21-28, 30-35, and 37-47 depend from claims 20, 29, and 36, respectively, and incorporate all the limitations of these claims. Accordingly, claims 20-47 are not entitled to the benefit of the prior application No. 61/238113, and will be examined as having an effective filing date of 08/28/2010.
Claim Rejections - 35 USC § 103
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 through 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.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 20-25, 29, 31-33, 36-39 and 41-42 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Schuchman (US 6,541,218, of record in IDS filed 06/03/2022, hereinafter “Schuchman”) in view of Fineman (Diabetes Metab Res Rev (2004); 20: 411-417, of record in Final Rejection on 02/10/2025) and Cheymol (Clinical pharmacokinetics 39 (2000): 215-231, of record in Non-Final Rejection on 09/05/2024).
Regarding claim 20, Schuchman teaches a method of treating a human patient with Type B Niemann Pick Disease comprising administering to the patient a therapeutically effective dose of a recombinant human acid sphingomyelinase (claim 4, column 6 lines 23-25, column 1 lines 31-32). Applicant discloses that Niemann Pick Type B disease is an ASM deficiency (ASMD) (specification page 2). Schuchman teaches that the therapeutically effective dose ranges from about 0.1 mg/kg body weight to about 2 mg/kg body weight (claim 6).
Schuchman does not teach an escalating dose regimen at the following sequential doses: (a) 0.1 mg/kg, (b) 0.3 mg/kg, and (c) 0.6 mg/kg; wherein each dose of rhASM is administered two weeks after the previous dose, wherein each dose is administered at least once before elevating the dose to the next level.
However, Fineman teaches progressive dose-escalation of a drug, and teaches the value of dose-escalation in mitigating the side effects by inducing drug tolerance (Abstract, Discussion). Fineman teaches that patients starting at higher dose and experiencing side effects were more likely to discontinue treatment than were those who started at a lower dose (Discussion).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Schuchman by administering the enzyme in a dose-escalating regimen and optimizing the doses and administration frequency, as suggested by Fineman. One of ordinary skill in the art would be motivated to do so in order to ensure the enzyme was well-tolerated and to mitigate the side effects by inducing drug tolerance. Since Schuchman and Fineman teach a desire to administer drugs to patients to treat diseases, there is a reasonable expectation of success.
While Schuchman and Fineman teach different doses than claimed, it would have been obvious to one of ordinary skill in the art to optimize the dose. Differences in concentrations do not support the patentability of subject matter encompassed by the prior art. 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. One of ordinary skill in the art would be motivated to optimize the dose in order to treat the patient.
Schuchman and Fineman do not teach wherein the weight of the human subject is calculated using the human subject's height if the human subject has a BMI > 30.
However, Cheymol teaches adaptation of drug dosages to obese human patients (Abstract), and teaches that obesity is a BMI >30 kg/m2 (page 217 left column para. 2). Cheymol teaches that ideal body weight (IBW), which is based mostly on height (page 217 left column, first incomplete paragraph), is used to calculate the dose in obese patients (page 220 right column para. 4, page 221 left column para.1, page 223 right column para. 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Schuchman by calculating the weight of the human subject using the human subject's height if the human subject has a BMI>30, as suggested by Cheymol. One of ordinary skill in the art would be motivated to do so in order to effectively and safely treat obese patients. Since Schuchman and Cheymol teach a desire to treat patients and administer appropriate doses, there is a reasonable expectation of success.
Regarding claims 21-23, Schuchman teaches a dose of 0.1 mg/kg body weight to about 2 mg/kg body weight or to about 10 mg/kg body weight (claims 5-6). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the dose in order to determine the optimal concentration of the enzyme to treat the disease while reducing side effects.
Regarding claim 24, Schuchman teaches the disease is Type B Niemann Pick Disease (claim 4).
Regarding claim 25, Schuchman teaches human adults with adult-onset form of the disease (column 31 lines 34-35). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Schuchman by administering the rhASM to adults with Type B Niemann Pick Disease as suggested by Schuchman. One of ordinary skill in the art would be motivated to do so in order to treat the disease in adult patients.
Regarding claim 29, Schuchman teaches a method of treating a human patient with Type B Niemann Pick Disease comprising administering to the patient a therapeutically effective dose of a recombinant human acid sphingomyelinase (claim 4, column 6 lines 23-25, column 1 lines 31-32). Applicant discloses Niemann-Pick Type B is an ASM deficiency (ASMD) (See specification page 2). Schuchman teaches the therapeutically effective dose ranges from about 0.1 μg/kg body weight to about 10 mg/kg body weight (claim 5).
Schuchman does not teach (b) administering successively higher doses of rhASM to the human subject if the human subject does not manifest a severe related adverse event, wherein each successively higher dose is from 0.1 mg/kg to 1 mg/kg higher than the previous dose, wherein each dose of rhASM is administered two weeks after the previous dose, wherein each dose is administered at least once before elevating the dose to the next level.
However, Fineman teaches progressive dose-escalation of a drug, and teaches the value of dose-escalation in mitigating the side effects by inducing drug tolerance (Abstract, Discussion page 415). Fineman teaches that patients starting at higher dose and experiencing side effects were more likely to discontinue treatment than were those who started at a lower dose (Discussion page 415).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Schuchman by administering the enzyme in a dose-escalating regimen and optimizing the doses and frequency, as suggested by Fineman. One of ordinary skill in the art would be motivated to do so in order to ensure that the enzyme is well-tolerated, and to mitigate the side effects by inducing drug tolerance. Since Schuchman and Fineman teach a desire to administer drugs to patients to treat diseases, there is a reasonable expectation of success.
Regarding claim 31, Schuchman teaches the disease is Type B Niemann Pick Disease (claim 4).
Regarding claim 32, Schuchman teaches human adults with adult-onset form of the disease (column 31 lines 34-35). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Schuchman by administering the rhASM to adults with Type B Niemann Pick Disease as suggested by Schuchman. One of ordinary skill in the art would be motivated to do so in order to treat the disease in the patients.
Regarding claim 33, Schuchman teaches a dose of 0.1 mg/kg body weight to about 2 mg/kg body weight or to about 10 mg/kg body weight (claims 5-6). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to vary and optimize the dose in order to determine the optimal concentration of the enzyme to treat the disease.
Regarding claim 36, Schuchman teaches a method of treating a human patient with Type B Niemann Pick Disease comprising administering to the patient a therapeutically effective dose of a recombinant human acid sphingomyelinase (claim 4, column 1 lines 31-32). Applicant discloses Niemann-Pick Type B is an ASM deficiency (ASMD) (See specification page 2). Schuchman teaches the therapeutically effective dose ranges from about 0.1 μg/kg body weight to about 10 mg/kg body weight (claim 5). Schuchman does not teach (b) subsequently, administering escalating doses of (i) 0.1 mg/kg, (ii) 0.3 mg/kg, and (iii) 0.6 mg/kg of rhASM to the human subject; wherein each dose of rhASM is administered two weeks after the previous dose, wherein each dose is administered at least once before elevating the dose to the next level.
However, Fineman teaches progressive dose-escalation of a drug, and teaches the value of dose-escalation in mitigating the side effects by inducing drug tolerance (Abstract, Discussion page 415). Fineman teaches that patients starting at higher dose and experiencing side effects were more likely to discontinue treatment than were those who started at a lower dose (Discussion page 415).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Schuchman by administering the enzyme in a dose-escalating regimen and optimizing the doses and administration frequency, as suggested by Fineman. One of ordinary skill in the art would be motivated to do so in order to ensure that the enzyme is well-tolerated and to mitigate the side effects by inducing drug tolerance. Since Schuchman and Fineman teach a desire to administer drugs and treat diseases, there is a reasonable expectation of success.
Regarding claims 37-39, Schuchman teaches a dose of 0.1 mg/kg body weight to about 2 mg/kg body weight or to about 10 mg/kg body weight (claims 5-6). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the dosage amount in order to determine the optimal concentration to treat the patient.
Regarding claim 41, Schuchman teaches the disease is Type B Niemann Pick Disease (claim 4).
Regarding claim 42, Schuchman teach adults with adult-onset form of the disease (column 31 lines 34-35). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Schuchman by administering the rhASM to adults with Type B Niemann Pick Disease as suggested by Schuchman. One of ordinary skill in the art would be motivated to do so in order to treat the patient.
Claims 26-28, 30, 34-35, 40 and 43-47 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Schuchman (US 6541218) in view of Fineman (Diabetes Metab Res Rev (2004); 20: 411-417) and Cheymol (Clinical pharmacokinetics 39 (2000): 215-231) as applied to claims 20, 29 and 36 above, and further in view of Miranda (The FASEB Journal 14.13 (2000): 1988-1995, of record in the Non-final Rejection on 09/05/2024).
Regarding claims 26, 30 and 40, Schuchman, Fineman and Cheymol do not teach that the doses are administered intravenously.
However, Miranda teaches that doses of 0.3, 1, 3, and 10 mg rhASM/kg of mouse body weight were administered intravenously (page 1989 para. “Enzyme administration”). Miranda teaches a rhASM dose-dependent clearance of sphingomyelin (Figure 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Schuchman by administering the enzyme intravenously as suggested by Miranda. One of ordinary skill in the art would be motivated to do so in order to effectively administer the enzyme. Since Schuchman and Miranda both teach a desire to administer the rhASM enzyme to patients, there is a reasonable expectation of success.
Regarding claims 27-28, 34-35 and 43-44, Miranda teaches a long-term protocol (i.e. maintenance dose regimen) using an intermediate dose of enzyme (1 mg/kg) injected once per week (i.e., administered to the subject every one to four weeks) (page 1991 left column para. “Long-term ERT”), and teaches that this protocol prevented significant sphingomyelin accumulation in organs compared to untreated subjects (page 1991 right column para. 1), and teaches that long-term treated subjects had markedly lower sphingomyelin levels than untreated, age-matched control subjects (page 1993 right column para. 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Schuchman by administering a weekly long-term intermediate dose regimen as suggested by Miranda. One of ordinary skill in the art would be motivated to do so in order to treat the patient and maintain a low sphingomyelin accumulation.
Regarding claims 45-47, while Miranda teaches a different long-term dose than claimed, it would have been obvious to one of ordinary skill in the art to optimize the maintenance dose. Differences in concentrations do not support the patentability of subject matter encompassed by the prior art. 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. One of ordinary skill in the art would be motivated to optimize the maintenance dose in order to prevent sphingomyelin accumulation, as suggested by Miranda.
Double Patenting
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 20-47 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-5 of U.S. Patent No. 6,541,218 in view of Miranda, Fineman and Cheymol.
Regarding instant claims 20, 29, and 36, patent claim 4 recites a method of treating a patient with Type B Niemann Pick Disease comprising administering to the patient a therapeutically effective dose of a recombinant human acid sphingomyelinase. Patent claim 5 recites the therapeutically effective dose ranges from about 0.1 μg/kg body weight to about 10 mg/kg body weight. Patent claims 4-5 do not recite the patient is a human and do not recite subsequently, administering escalating doses of (i) 0.1 mg/kg, (ii) 0.3 mg/kg, and (iii) 0.6 mg/kg of rhASM to the human subject; wherein each dose of rhASM is administered two weeks after the previous dose, wherein each dose is administered at least once before elevating the dose to the next level.
However, Miranda teaches Type B Niemann Pick Disease affects humans (page 1988 right column first para).
Fineman teaches progressive dose-escalation of a drug, and teaches the value of dose-escalation in mitigating the side effects by inducing drug tolerance (Abstract, Discussion). Fineman teaches that patients starting at higher dose and experiencing side effects were more likely to discontinue treatment than were those who started at a lower dose (Discussion).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited in patent claims 4-5 by administering the enzyme to a human in a dose-escalating regimen and optimizing the doses and administration frequency, as suggested by Miranda and Fineman. One of ordinary skill in the art would be motivated to do so in order to treat the human patient while reducing side effects.
Patent claims 4-5 do not recite wherein the weight of the human subject is calculated using the human subject's height if the human subject has a BMI > 30. However, Cheymol teaches adaptation of drug dosages to obese human patients (Abstract), and teaches that obesity is a BMI >30 kg/m2 (page 217 left column para. 2). Cheymol teaches that ideal body weight (IBW), which is based mostly on height (page 217 left column, first incomplete paragraph), is used to calculate the dose in obese patients (page 220 right column para. 4, page 221 left column para.1, page 223 right column para. 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited in patent claims 4-5 by calculating the weight of the subject using the subject's height if the subject has a BMI > 30 as suggested by Cheymol. One of ordinary skill in the art would be motivated to do so in order to optimize the drug dosages to obese human patients as taught by Cheymol.
Regarding instant claims 21-23, 33, and 37-39, patent claim 5 recites a dose of 0.1 mg/kg body weight to about 2 mg/kg body weight or to about 10 mg/kg body weight (claims 5-6). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the dose in order to determine the optimal amount of the enzyme to treat the disease.
Regarding instant claims 24, 31, and 41, patent claim 4 recites the disease is Type B Niemann Pick Disease.
Regarding instant claims 25, 32, and 42, patent claims 4-5 do not recite human adult. However, Miranda teaches the disease affects infants, adolescents and adults (page 1988 right column first para.).
Regarding instant claims 26, 30, and 40, patent claims 4-5 do not recite the doses are administered intravenously. However, Miranda teaches doses of 0.3, 1, 3, and 10 mg rhASM/kg of mouse body weight were administered intravenously (page 1989 para. “Enzyme administration”. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method recited in patent claims 4-5 by administering the enzyme intravenously as suggested by Miranda. One of ordinary skill in the art would be motivated to do so since Miranda teaches at such doses the enzyme can be administered intravenously and this route of administration is effective.
Regarding instant claims 27-28, 34-35, and 43-44, Miranda teaches a long-term protocol (i.e. maintenance dose regimen) using an intermediate dose of enzyme (1 mg/kg) (i.e., a dose equal to or less than the highest dose tolerated by the subject) injected once per week (i.e., administered to the subject every one to four weeks) (page 1991 left column para. “Long-term ERT”), and teaches this protocol prevented significant SPM accumulation in organs compared to untreated subjects (page 1991 right column para. 1). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method recited in patent claims 4-5 by administering a long-term intermediate dose regimen weekly as suggested by Miranda. One of ordinary skill in the art would be motivated to do so since Miranda teaches such regimen was beneficial in lower substrate levels compared to untreated subjects
Regarding instant claims 45-47, while Miranda teaches a different long-term dose than claimed, it would have been obvious to one of ordinary skill in the art to optimize the maintenance dose. Differences in concentrations do not support the patentability of subject matter encompassed by the prior art. 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. One of ordinary skill in the art would be motivated to optimize the maintenance dose in order to prevent sphingomyelin accumulation, as suggested by Miranda.
Claims 20-26, 29-33 and 36-42 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 7 of U.S. Patent No. 8,658,162 in view of Cheymol.
Regarding instant claims 20-23, 29, 33, and 36-39, patent claim 1 recites a method for treating a human subject having an acid sphingomyelinase deficiency (ASMD), comprising: (a) administering at least one initial dose of recombinant human acid sphingomyelinase (rhASM) to the human subject, wherein the initial dose is from 0.025 mg/kg to 0.275 mg/kg; and (b) subsequent to the administration of the at least one initial dose, administering a higher dose of rhASM to the human subject, wherein the higher dose is from 0.1 mg/kg to 3 .0 mg/kg higher than the initial dose. Patent claim 2 recites wherein the higher dose is from 0.5mg/kg to 2 mg/kg higher than the initial dose. Patent claim 3 recites wherein the higher dose is from 2 mg/kg to 4 mg/kg higher than the initial dose. Patent claim 4 recites wherein each dose is administered one, two, three, or four weeks after the previous dose. One of ordinary skill in the art would be motivated to optimize the dose and the frequency of administrating the enzyme in order to effectively and safely treat the patient. Patent claims 1-4 do not recite wherein the weight of the human subject is calculated using the human subject's height if the human subject has a BMI > 30.
However, Cheymol teaches adaptation of drug dosages to obese human patients (Abstract), and teaches that obesity is a BMI >30 kg/m2 (page 217 left column para. 2). Cheymol teaches that ideal body weight (IBW), which is based mostly on height (page 217 left column, first incomplete paragraph), is used to calculate the dose in obese patients (page 220 right column para. 4, page 221 left column para.1, page 223 right column para. 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited in patent claims 1-4 by optimizing the dose and calculating the weight of the human subject using the subject's height if the subject has a BMI > 30 as suggested by Cheymol. One of ordinary skill in the art would be motivated to do so in order to optimize the drug dosages to obese human patients as taught by Cheymol.
Regarding instant claims 24, 31, and 41, patent claim 7 recites wherein the ASMD is NPD type B.
Regarding instant claims 25, 32, and 42, patent claims 1-4 do not recite human adult. However, one of ordinary skill in the art would be motivated to administer the enzyme to human adults in order to treat the disease.
Regarding instant claims 26, 30, and 40, patent claim 5 recites wherein the doses are administered intravenously.
Claims 27-28, 34-35 and 43-47 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 7 of U.S. Patent No. 8,658,162 in view of Cheymol and Miranda.
Regarding claims 27-28, 34-35, and 43-44, patent claims 1-5 and 7 do not recite a maintenance dose regimen comprising administering a dose equal to or less than the highest dose tolerated by the human subject as the maintenance dose for the human subject.
However, Miranda teaches a long-term protocol (i.e. maintenance dose regimen) using an intermediate dose of enzyme (1 mg/kg) (i.e., a dose equal to or less than the highest dose tolerated by the subject) injected once per week (i.e., administered to the subject every one to four weeks) (page 1991 left column para. “Long-term ERT”), and teaches that this protocol prevented significant sphingomyelin accumulation in organs compared to untreated subjects (page 1991 right column para. 1). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method recited in patent claims 1-5 and 7 by administering a long-term intermediate dose regimen weekly as suggested by Miranda. One of ordinary skill in the art would be motivated to do so in order to treat the patient and maintain a low sphingomyelin accumulation.
Regarding claims 45-47, Miranda teaches a long-term dose of 1 mg/kg. One of ordinary skill in the art would be motivated to optimize the maintenance dose in order to prevent sphingomyelin accumulation, as suggested by Miranda.
Claims 20-26, 29-33 and 36-42 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6 and 8 of U.S. Patent No. 8,709,408 in view of Cheymol.
Regarding instant claims 20-23, 29, 33, and 36-39, patent claim 1 recites a method for treating a human subject having an acid sphingomyelinase deficiency (ASMD), comprising: (a) administering at least one initial dose of recombinant human acid sphingomyelinase (rhASM) to the human subject, wherein the initial dose is from 0.025 mg/kg to 0.275 mg/kg; and (b) if the plasma ceramide concentration of the human subject is equal to or less than 10 μg/mL after the administration of the at least one initial dose, administering a higher dose of rhASM to the human subject. Patent claim 4 recites wherein the higher dose is from 0.1 mg/kg to 1 mg/kg, 0.5 mg/kg to 2 mg/kg, or 2 mg/kg to 4 mg/kg higher than the one or more initial doses. Patent claim 5 recites wherein each dose is administered one, two, three, or four weeks after the previous dose. One of ordinary skill in the art would be motivated to optimize the dose and frequency in order to effectively and safely treat the patient. Patent claims 1 and 4-5 do not recite wherein the weight of the human subject is calculated using the human subject's height if the human subject has a BMI > 30.
However, Cheymol teaches adaptation of drug dosages to obese human patients (Abstract), and teaches that obesity is a BMI >30 kg/m2 (page 217 left column para. 2). Cheymol teaches that ideal body weight (IBW), which is based mostly on height (page 217 left column, first incomplete paragraph), is used to calculate the dose in obese patients (page 220 right column para. 4, page 221 left column para.1, page 223 right column para. 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited in patent claims 1 and 4-5 by calculating the weight of the subject using the subject's height if the subject has a BMI > 30 as suggested by Cheymol. One of ordinary skill in the art would be motivated to do so in order to optimize the drug dosages to obese human patients as taught by Cheymol.
Regarding instant claims 24, 31, and 41, patent claim 8 recites wherein the ASMD is NPD type B.
Regarding instant claims 25, 32 and 42, patent claims 1 and 4-5 do not recite human adult. However, one of ordinary skill in the art would be motivated to administer the enzyme to human adults in order to treat the disease.
Regarding instant claims 26, 30, and 40, patent claim 6 recites wherein the doses are administered intravenously.
Claims 27-28, 34-35 and 43-47 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6 and 8 of U.S. Patent No. 8,709,408 in view of Cheymol and Miranda.
Regarding claims 27-28, 34-35, and 43-44, patent claims 1, 4-6 and 8 do not recite a maintenance dose regimen comprising administering a dose equal to or less than the highest dose tolerated by the human subject as the maintenance dose for the human subject.
However, Miranda teaches a long-term protocol (i.e. maintenance dose regimen) using an intermediate dose of enzyme (1 mg/kg) (i.e., a dose equal to or less than the highest dose tolerated by the subject) injected once per week (i.e., administered to the subject every one to four weeks) (page 1991 left column para. “Long-term ERT”), and teaches that this protocol prevented significant sphingomyelin accumulation in organs compared to untreated subjects (page 1991 right column para. 1), and teaches that long-term treated subjects had markedly lower sphingomyelin levels than untreated, age-matched control subjects (page 1993 right column para. 2). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method recited in patent claims 1, 4-6 and 8 by administering a long-term intermediate dose regimen weekly as suggested by Miranda. One of ordinary skill in the art would be motivated to do so in order to treat the patient and maintain a low sphingomyelin accumulation.
Regarding claims 45-47, Miranda teaches a long-term dose of 1 mg/kg. One of ordinary skill in the art would be motivated to optimize the maintenance dose to prevent sphingomyelin accumulation, as suggested by Miranda.
Claims 20-26, 29-33 and 36-42 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 9,114,139 in view of Cheymol.
Regarding instant claims 20-23, 29, 33, and 36-39, patent claim 1 recites a method for reducing sphingomyelin accumulation in one or more organs of a human subject having an acid sphingomyelinase deficiency (ASMD), comprising administering at least one initial dose of recombinant human acid sphingomyelinase (rhASM) to the human subject, wherein the initial dose is from 0.025 mg/kg to 0.275 mg/kg; and subsequent to the administration of the at least one initial dose, administering a higher dose of rhASM to the human subject, wherein the higher dose is from 0.1 mg/kg to 3 .0 mg/kg higher than the initial dose. Patent claim 2 recites administering a higher dose of rhASM to the human subject, wherein the higher dose is from 0.5 mg/kg to 2 mg/kg higher than the initial dose. Patent claims 3-4 recite wherein each dose is administered one, two, three, or four weeks after the previous dose. One of ordinary skill in the art would be motivated to optimize the dose and the frequency of administering the enzyme in order to effectively and safely treat the patient. Patent claims 1-4 do not recite wherein the weight of the human subject is calculated using the human subject's height if the human subject has a BMI > 30.
However, Cheymol teaches adaptation of drug dosages to obese human patients (Abstract), and teaches that obesity is a BMI >30 kg/m2 (page 217 left column para. 2). Cheymol teaches that ideal body weight (IBW), which is based mostly on height (page 217 left column, first incomplete paragraph), is used to calculate the dose in obese patients (page 220 right column para. 4, page 221 left column para.1, page 223 right column para. 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited in patent claims 1-4 by calculating the weight of the human subject using the subject's height if the subject has a BMI > 30, as suggested by Cheymol. One of ordinary skill in the art would be motivated to do so in order to effectively and safely treat obese patients.
Regarding instant claims 24, 31, and 41, patent claims 7-8 recite wherein the ASMD is NPD type B.
Regarding instant claims 25, 32, and 42, patent claims 1-4 do not recite human adult. However, one of ordinary skill in the art would be motivated to administer the enzyme to human adults in order to treat the disease.
Regarding instant claims 26, 30, and 40, patent claims 5-6 recite wherein the doses are administered intravenously.
Claims 27-28, 34-35, and 43-47 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 9,114,139 in view of Cheymol and Miranda.
Regarding instant claims 27-28, 34-35, and 43-44, patent claims 1-8 do not recite a maintenance dose regimen comprising administering a dose equal to or less than the highest dose tolerated by the human subject as the maintenance dose for the human subject.
However, Miranda teaches a long-term protocol (i.e. maintenance dose regimen) using an intermediate dose of enzyme (1 mg/kg) (i.e., a dose equal to or less than the highest dose tolerated by the subject) injected once per week (i.e., administered to the subject every one to four weeks) (page 1991 left column para. “Long-term ERT”), and teaches that this protocol prevented significant sphingomyelin accumulation in organs compared to untreated subjects (page 1991 right column para. 1). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method recited in patent claims 1-8 by administering a long-term intermediate dose regimen weekly as suggested by Miranda. One of ordinary skill in the art would be motivated to do so in order to treat the patient and maintain a low sphingomyelin accumulation.
Regarding instant claims 45-47, Miranda teaches a long-term dose of 1 mg/kg. One of ordinary skill in the art would be motivated to optimize the maintenance dose in order to prevent sphingomyelin accumulation, as suggested by Miranda.
Claims 20-47 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 7 and 19-20 of U.S. Patent No. 9,655,954 in view of Schuchman and Cheymol.
Regarding instant claims 20-23, 29, 33 and 36-39, patent claim 19 recites a method for treating a human subject having an acid sphingomyelinase deficiency, comprising administering recombinant human acid sphingomyelinase (rhASM) in an escalating dose regimen at the following sequential doses: a. 0.3 mg/kg; b. 1 mg/kg; and c. 3 mg/kg; wherein each dose of rhASM is administered at two week intervals, wherein each dose is administered at least once before elevating the dose to the next level, and wherein the subject is monitored for toxic side effects before elevating the dose to the next level. Patent claim 1 recites administering at least one initial dose of recombinant human acid sphingomyelinase (rhASM) to the human subject, wherein the initial dose is 0.3 mg/kg; and (b) subsequent to the administration of the at least one initial dose, administering a higher dose of rhASM to the human subject if the human subject does not experience a severe related adverse event, wherein the higher dose is from 0.1 mg/kg to 3.0 mg/kg higher than the initial dose. Patent claim 3 recites wherein each dose is administered one, two, three, or four weeks after the previous dose. It is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art.
Patent claims 1, 3 and 19 do not recite initial dose of 0.1 mg/kg or 0.025 m/kg to 0.05 mg/kg of rhASM.
However, Schuchman teaches the therapeutically effective dose of rhASM ranges from about 0.1 μg/kg body weight to about 10 mg/kg body weight (claim 5).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited in patent claims 1, 3 and 19 by optimizing the administered dose as suggested by Schuchman. One of ordinary skill in the art would be motivated to do so in order to treat the patient. Since Schuchman teaches rhASM has a therapeutic effect even at very low doses, there is a reasonable expectation of success.
Patent claims 1, 3 and 19 do not recite wherein the weight of the human subject is calculated using the human subject's height if the human subject has a BMI > 30.
However, Cheymol teaches adaptation of drug dosages to obese human patients (Abstract), and teaches that obesity is a BMI >30 kg/m2 (page 217 left column para. 2). Cheymol teaches that ideal body weight (IBW), which is based mostly on height (page 217 left column, first incomplete paragraph), is used to calculate the dose in obese patients (page 220 right column para. 4, page 221 left column para.1, page 223 right column para. 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited in patent claims 1, 3 and 19 by calculating the weight of the subject using the subject's height if the subject has a BMI > 30 as suggested by Cheymol. One of ordinary skill in the art would be motivated to do so in order to optimize the drug dosages to obese human patients as taught by Cheymol. Since Cheymol teaches a desire to safely and effectively treat obese human patients, there is a reasonable expectation of success.
Regarding instant claims 24, 31 and 41, patent claim 7 recites the acid sphingomyelinase deficiency is NPD type B.
Regarding instant claims 25, 32 and 42, patent claims 1, 3 and 19 do not recite human adult. However, Schuchman teach adults with adult-onset form of the disease (column 31 lines 34-35). One of ordinary skill in the art would be motivated to administer the enzyme to human adults in order to treat the disease.
Regarding instant claims 26, 30 and 40, patent claim 5 recites the doses are administered intravenously.
Regarding instant claims 27 and 34, patent claim 20 recites the method further comprising a maintenance dose regimen comprising administering a dose equal to or less than the highest dose tolerated by the subject as the maintenance dose for the subject.
Regarding instant claims 28, 35 and 43-44, patent claim 3 recites the dose is administered one, two, three, or four weeks after the previous dose. One of ordinary skill in the art would be motivated to optimize the frequency of administering the enzyme in order to safely and effectively treat the patient.
Regarding instant claims 45-47, Miranda teaches a long-term dose of 1 mg/kg. One of ordinary skill in the art would be motivated to optimize the maintenance dose in order to safely and effectively treat the patient and maintain a low sphingomyelin accumulation.
Claims 20-47 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 12, 14, 27, 37-38, 40, and 43 of U.S. Patent No. 10,188,705 in view of Cheymol.
Regarding instant claims 20-23, 29, 33, and 36-39, patent claim 1 recites a method for treating an acid sphingomyelinase deficiency (ASMD), comprising: a. administering to a human subject in need thereof one or more initial doses of 0.1 mg/kg recombinant human acid sphingomyelinase (rhASM); and b. administering sequentially escalating higher doses of rhASM to the human subject if the subject does not manifest one or more moderate or severe adverse events, wherein the higher doses are from 0.1 mg/kg to 1.0 mg/kg higher than the previous dose. Patent claim 2 recites a method for treating an acid sphingomyelinase deficiency (ASMD), comprising intravenously administering to a human subject in need thereof recombinant human acid sphingomyelinase (rhASM) in an escalating dose regimen at the following sequential doses: a. 0.1 mg/kg, b. 0.3 mg/kg, c. 0.6 mg/kg, and d. 1 mg/kg. Patent claim 5 recites a method for treating an acid sphingomyelinase deficiency (ASMD), comprising: a. a dose escalation regimen comprising: i. administering to a human subject in need thereof a dose ranging from 0.001 mg/kg to 0.05 mg/kg rhASM; and ii. administering successively higher doses of rhASM to the human subject if the human subject does not manifest one or more moderate or severe adverse events; and b. a maintenance regimen comprising administering a maintenance dose of 1, 2, or 3 mg/kg rhASM to the human subject. Patent claim 38 recites wherein the method comprises a further sequential dose of 2 mg/kg rhASM. Patent claim 40 recites wherein the method comprises a further sequential dose of 3 mg/kg rhASM. One of ordinary skill in the art would be motivated to optimize the dose and frequency in order to effectively and safely treat the patient. Patent claims 1-2, 5, 38 and 40 do not recite wherein the weight of the human subject is calculated using the human subject's height if the human subject has a BMI>30.
However, Cheymol teaches adaptation of drug dosages to obese human patients (Abstract), and teaches that obesity is a BMI >30 kg/m2 (page 217 left column para. 2). Cheymol teaches that ideal body weight (IBW), which is based mostly on height (page 217 left column, first incomplete paragraph), is used to calculate the dose in obese patients (page 220 right column para. 4, page 221 left column para.1, page 223 right column para. 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited in patent claims 1-2, 5, 38 and 40 by calculating the weight of the human subject using the human subject's height if the subject has a BMI > 30 as suggested by Cheymol. One of ordinary skill in the art would be motivated to do so in order to effectively treat obese patients.
Regarding instant claims 24, 31, and 41, patent claim 14 recites wherein the ASMD is NPD type B.
Regarding instant claims 25, 32, and 42, patent claim 27 recites the human subject is a human adult.
Regarding instant claims 26, 30, and 40, patent claim 12 recites wherein the doses are administered intravenously.
Regarding instant claims 27, 34, 43 and 45-47, patent claim 5 recites the method comprises a maintenance regimen comprising administering a maintenance dose of 1, 2, or 3 mg/kg rhASM to the human subject. Patent claim 37 recites the maintenance dose is the highest dose tolerated by the human subject.
Regarding instant claims 28, 35, and 44, patent claim 43 recites wherein the maintenance dose is administered every two weeks.
Response to Arguments
Applicant's arguments filed 12/22/2025 have been fully considered but they are not persuasive.
Applicant argues that Schuchman does not teach treating a human subject with an escalating dose regimen. Applicant argues that Fineman and Cheymol do not teach treating a human subject having an ASMD or using rhASM as a treatment for ASMD. Applicant argues that the dose escalation study described in Fineman was used to mitigate gastrointestinal side effects of exenatide, such as to reduce nausea and vomiting. Applicants argues that the toxicity problem associated with administering a dose of rhASM as low as 0.3 mg/kg was not known.
Applicant argues the Office Action impermissibly relies on the teaching in the present application to cobble together disclosure of the referenced prior art.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, Schuchman teaches treating Niemann-Pick Type B disease in humans by administering rhASM enzyme and teaches that the therapeutically effective dose ranges from about 0.1 mg/kg body weight to about 2 mg/kg body weight. Fineman teaches that dose escalation is used in the field to mitigate the side effects by inducing drug tolerance. Thus, Fineman teaches an advantage of administering drugs using dose escalation regimen which results in patient compliance and lower chances of discontinuing the treatment. One of ordinary skill in the art would recognize an advantage of combining the teachings of Schuchman and Fineman.
Cheymol teaches adaptation of drug dosages to obese human patients (Abstract), and teaches that obesity is a BMI >30 kg/m2 (page 217 left column para. 2). Cheymol teaches that ideal body weight (IBW), which is based mostly on height (page 217 left column, first incomplete paragraph), is used to calculate the dose in obese patients (page 220 right column para. 4, page 221 left column para.1, page 223 right column para. 3). Since Fineman and Cheymol teach a desire to safely administer drugs to patients, there is a reasonable expectation of success.
Since the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. One of ordinary skill in the art would be motivated to administer the enzyme following an escalating dose regiment as suggested by Fineman, and to optimize the dose taught by Schuchman, as suggested by Cheymol in order to safely and effectively treat the obese human patient.
Applicant argues that Miranda teaches the mouse received the same dose for every administration throughout the study and does not teach escalating dose regimen.
In response to the argument, Miranda is relied upon for teaching the intravenous administration and the maintenance dose. In addition, Miranda teaches that every dose had an effect on lowering sphingomyelin levels. Thus, one of ordinary skill in the art would recognize low dosage would lower sphingomyelin levels.
Applicant argues claims 4-5 of US 6,451,218 do not recite administering rhASM at the escalating doses of the claimed invention and argues Cheymol nor Miranda teach or suggest a dose escalation treatment regimen.
In response to the argument, based on the teachings of Fineman, one of ordinary skill in the art would be motivated to administer the recited enzyme in an escalating dose regimen in order to reduce the side effects in a subject and induce drug tolerance, and to optimize the dose depending on the patient’s height if BMI>30 as suggested by Cheymol.
Applicant argues that claims 1, 4, 5, and 7 of US 8,658,162 do not recite the administration of escalating doses and wherein the weight of the subject is calculated using the subject's height if the subject has a BMI > 30, and argues that Cheymol would not have rendered the claimed methods obvious.
In response to the argument, patent claim 1 recites an initial non-toxic dose, followed by higher doses while monitoring for one or more adverse side effects after each successive dose (i.e., dose escalation regiment). Patent claims 2 and 3 recite dose is from 0.025 mg/kg to 0.275 mg/kg, the higher dose is from 0.5 mg/kg to 2 mg/kg or rom 2 mg/kg to 4 mg/kg higher than the initial dose, respectively. One of ordinary skill in the art would be motivated to optimize the doses as well as the frequency of administering the doses in order to safely and effectively treat the patient. Based on the teachings of Cheymol, one of ordinary skill in the art would be motivated to optimize the dose for obese human patients. Since Cheymol teaches optimizing drug dosages to obese patients, there is a reasonable expectation of success.
Applicant argues that 1) claims 1, 4-6, and 8 of the US 8,709,408 do not recite the administration of escalating doses of 0.1 mg/kg, 0.3 mg/kg, and 0.6 mg/kg of rhASM to a human subject having an ASMD, as required by claims 20 and 36 of the present application and claims dependent therefrom, 2) claims 1, 4-6, and 8 of the '408 Patent do not recite administration of successively higher doses of 0.3 mg/kg, 0.6 mg/kg, 1 mg/kg, 2 mg, and 3 mg/kg, as required by claim 29 of the present application and claims dependent therefrom, 3) none of the claims recite a method for treating a human subject having an ASMD comprising administering to the human subject recombinant human acid sphingomyelinase (rhASM) in an escalating dose regimen recited in the claimed methods, wherein the weight of the subject is calculated using the subject's height if the subject has a BMI > 30, and argues that Cheymol would not have rendered the claimed methods obvious.
In response to the argument, patent claim 1 recites an initial dose, followed by higher doses if the patient does not show adverse side effects (i.e., escalating dose regimen). Patent claim 4 recites wherein the higher dose is from 0.1 mg/kg to 1 mg/kg, 0.5 mg/kg to 2 mg/kg, or 2 mg/kg to 4 mg/kg higher than the one or more initial doses. One of ordinary skill in the art would be motivated to optimize the doses as well as the frequency of administering the doses in order to safely and effectively treat the patient. In addition, one of ordinary skill in the art would be motivated to optimize the dose for obese patients as suggested by Cheymol. Since Cheymol teaches a desire to optimize drug dosages to obese human patients, there is a reasonable expectation of success.
Applicant argues that 1) claims 1-8 of US 9,114,139 do not recite the administration of escalating doses wherein the weight of the subject is calculated using the subject's height if the subject has a BMI > 30, and argues that Cheymol would not have rendered the claimed methods obvious.
In response to the argument, patent claim 1 recites a) administering at least one initial dose of recombinant human acid sphingomyelinase (rhASM) to the human subject, wherein the initial dose is from 0.025 mg/kg to 0.275 mg/kg; and b) subsequent to the administration of the at least one initial dose, administering a higher dose of rhASM to the human subject, wherein the higher dose is from 0.1 mg/kg to 3 .0 mg/kg higher than the initial dose (i.e., escalating dose regimen). Patent claim 2 recites wherein the higher dose is from 0.5 mg/kg to 2 mg/kg higher than the initial dose. One of ordinary skill in the art would be motivated to optimize the doses as well as the frequency of administering the doses in order to safely and effectively treat the patient. Based on the teachings of Cheymol, one of ordinary skill in the art would be motivated to optimize the dose for obese patients. Since Cheymol teaches a desire to optimize drug dosages to obese human patients, there is a reasonable expectation of success.
Applicant argues claims of US 9,655,954 recite administering an initial dose of 0.3 mg/kg and do not recite administration of a dose of 0.1 mg/kg of rhASM or a dose of 0.025 mg/kg to 0.05 mg/kg of rhASM, and argues the claims do not recite wherein the weight of the subject is calculated using the subject's height if the subject has a BMI > 30.
In response to the argument, Schuchman teaches the therapeutically effective dose of rhASM ranges from about 0.1 μg/kg body weight to about 10 mg/kg body weight (claim 5). One of ordinary skill in the art would be motivated to optimize the dose and the frequency of administration of the enzyme in order to effectively and safely treat the patient. Since Schuchman teaches rhASM has a therapeutic effect even at very low doses, there is a reasonable expectation of success. Based on the teachings of Cheymol, one of ordinary skill in the art would be motivated to optimize the dose for obese patients. Since Cheymol teaches a desire to optimize drug dosages to obese human patients, there is a reasonable expectation of success.
Applicant argues claims 2, 5, 12, 14, 27, 32, 37, 38, 40, and 43 of US 10,188,705 do not teach or suggest a method for treating a human subject having an ASMD comprising administering to the human subject rhASM in an escalating dose regimen recited in the claimed methods, wherein the weight of the subject is calculated using the subject's height if the subject has a BMI > 30, and argues that Cheymol would not have rendered the claimed methods obvious.
In response to the argument, patent claim 1 recites initial doses of 0.1 mg/kg of rhASM and sequentially escalating higher doses from 0.1 mg/kg to 1.0 mg/kg higher than the previous dose. Patent claim 2 recites and escalating dose regimen of a. 0.1 mg/kg, b. 0.3 mg/kg, c. 0.6 mg/kg, and d. 1 mg/kg. Patent claim 5 recites dose escalation regimen comprising: i. administering to a human subject in need thereof a dose ranging from 0.001 mg/kg to 0.05 mg/kg rhASM; and ii. administering successively higher doses of rhASM to the human subject if the human subject does not manifest one or more moderate or severe adverse events. One of One of ordinary skill in the art would be motivated to optimize the dose and the frequency of administration of the enzyme in order to effectively and safely treat the patient. One of ordinary skill in the art would be motivated to optimize the dose for obese human patients, as suggested by Cheymol. Since Cheymol teaches a desire to optimize drug dosages for safely treating obese human patients, there is a reasonable expectation.
Conclusion
THIS ACTION IS MADE FINAL. 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 MARY A CRUM whose telephone number is (571)272-1661. The examiner can normally be reached M-F 8:00-5:00 CT with alternate Fridays off.
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, LOUISE W HUMPHREY can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MARY A CRUM/Examiner, Art Unit 1657
/THANE UNDERDAHL/Primary Examiner, Art Unit 1699
Prosecution Insights