DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/6/26 has been entered.
Election/Restrictions and Claim Status
Applicants’ amendments and arguments filed 1/6/26 are acknowledged.
Previously, compound 102 was elected. The elected species was found in the prior art and claims drawn to the elected species are rejected as set forth below.
Claims 1-48 and 59 have been cancelled.
Claims 49-58 and 60-61 are being examined.
Priority
The priority information is found in the filing receipt dated 4/1/20.
Claim Rejections - 35 USC § 103
Claims were previously rejected based on the references cited below. Since the claims have been amended the rejection is updated to correspond to the instant claim.
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 negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 49-58 and 60-61 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Reaume et al. (US 2007/0093516; ‘Reaume’; cited with IDS 4/2/20) in view of Raj et al. (‘Oral Insulin – A Perspective’ Journal of Biomaterials Applications v17 Jan 2003 pages 183-196; cited with IDS 4/2/20; ‘Raj’) in view of DeWitt et al. (‘Outpatient insulin therapy in type 1 and type 2 diabetes mellitus’ JAMA v289(17) May 7 2003 pages 2254-2264 and pages e1-e7 for a total of 18 pages; ‘DeWitt’; cited with IDS 4/2/20).
Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Reaume specifically teach methods for reducing blood glucose levels (section 0008). Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014). Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Reaume teach that insulin signals the liver to stop making sugars (sections 0116-0117). Reaume teach that the compounds of the invention direct the modulation of lyn kinase in the insulin receptor pathway (section 0006). Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach the inclusion of a fibrate with the composition (section 0143).
Reaume does not further describe those with insulin dependent diabetes mellitus nor does Reaume administer both insulin and the compound of the formula as recited in the claims to a subject as claimed.
Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells, the only cells in the body that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Raj teach that diabetes mellitus can be controlled quite well with insulin injections (page 185 2nd complete paragraph).
DeWitt teach insulin therapies for type 1 diabetes (title). DeWitt teach the use of intravenous injection of insulin (page 2255 last complete paragraph). In the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3). As shown in figure 1a, the long-acting insulin glargine is known to be administered. DeWitt teach advantages of using glargine (page 2254 section data synthesis) and also recognize the use of other insulin products (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption). DeWitt teach that the peak of the insulin product can be as little as 30-90 minutes (Table 1).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of Reaume because Reaume expressly teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104). Since Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148) one would have been motivated to administer the specific insulins based on the methods taught by DeWitt and to the patients as taught by Raj. Thus based on the nature of the problem to be solved (i.e. treating type 1 diabetes) and the specific suggestions of Reaume one would be motivated to administer appropriate compounds. Since Reaume teach the inclusion of a fibrate with the composition (section 0143) one would have been motivated to do such. With respect to the timing, DeWitt teach that the peak of the insulin product can be as little as 30-90 minutes (Table 1). Since Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141) one would have been motivated to optimize the timing of the administration. One would have had a reasonable expectation of success since Reaume expressly teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) and in the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3). Further, Raj teach that diabetes mellitus can be controlled quite well with insulin injections (page 185 2nd complete paragraph).
In KSR, the Supreme Court particularly emphasized "the need for caution in granting a patent based on the combination of elements found in the prior art,"Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that "[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results."Id. at 415-16, 82 USPQ2d at 1395. In the instant case, the claims relate to the administration of known agents according to known methods. In fact, DeWitt is a review article about insulin therapies for type 1 diabetes (title).
MPEP 2112.02 II recognizes that new and obvious uses of old structures may be patentable. However when the use is directed to a result or property of that composition then the claim is not patentable. In the instant case, the blood glucose effects of MLR-1023 were known as Reaume specifically teach methods for reducing blood glucose levels (section 0008).
In relation to the patient population as recited in claims 49, 53 and 60, Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Thus, one would have been motivated to administer to those with diabetes including those with beta-cells that produce no insulin. Further, DeWitt teach insulin therapies for type 1 diabetes (title).
In relation to the insulin as recited in claims 49, 55-57 and 60, DeWitt teach using glargine (page 2254 section data synthesis) which is long acting (table 1) and also recognize the use of other insulin products including rapid and short acting (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption). DeWitt teach once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3) and the use of intravenous injection of insulin (page 225 last complete paragraph) thus suggesting bolus injection.
In relation to the compound of formula I as recited in claims 49-52, 54, 58 and 60, Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). As shown in section 0088 of Reaume compound 102 is applicants’ elected species and meets the structural requirements as claimed. Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014).
In relation to the sequential administration as in claims 49 and 60, Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Further, since Reaume specifically teach methods for reducing blood glucose levels (section 0008) one would be motivated to optimize the timing to achieve such goal (MPEP 2144.05 IIB). DeWitt teach that the peak of the insulin product can be as little as 30-90 minutes (Table 1).
In relation to claim 61, Reaume teach the inclusion of a fibrate with the composition (section 0143).
In relation to the outcomes recited in the last 3 lines of claim 49 and the last 4 lines of claim 60 and the intended uses of the first 3 lines of claim 49 and 60, the prior art suggest the agents as claimed so they would function as claimed. Further, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach that the compounds direct the modulation of lyn kinase in the insulin receptor pathway and lyn activation has insulin receptor activation like activity (sections 0006, 0032 and 0091 and figure 12). Reaume specifically teach the compounds up-regulate the expression and/or activity of lyn kinase (section 0059). Further, Reaume (example 4 and figure 9) shows that specific doses of compound 102 reduced blood glucose levels (section 0179 and figure 9) and teach that the blood glucose levels were measured 2 hours (120 minutes) after the injection (section 0177).
Response to Arguments - 103
Applicant's arguments filed 1/6/26 have been fully considered but they are not persuasive.
Although applicants argue that Reaume alone does not teach the claim limitations, the instant rejection is a multiple reference 103 rejection and as such any single reference does not necessarily anticipate the claims. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Although applicants argue about performance between 1.5 to 6 hours, it is first noted that the active step of the claims is ‘administration’. In relation to the outcomes recited in the last 3 lines of claim 49 and the last 4 lines of claim 60 and the intended uses of the first 3 lines of claim 49 and 60, the prior art suggest the agents as claimed so they would function as claimed. Further, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach that the compounds direct the modulation of lyn kinase in the insulin receptor pathway and lyn activation has insulin receptor activation like activity (sections 0006, 0032 and 0091 and figure 12). Reaume specifically teach the compounds up-regulate the expression and/or activity of lyn kinase (section 0059). Further, Reaume (example 4 and figure 9) shows that specific doses of compound 102 reduced blood glucose levels (section 0179 and figure 9) and teach that the blood glucose levels were measured 2 hours (120 minutes) after the injection (section 0177).
Although applicants argue that the application demonstrates unexpected results in the form of synergy and that Reaume only broadly discloses synergy, MPEP 716.02(a) recognizes that a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such effect can either be expected or unexpected. Applicants’ example 3 refers to the compound prolonging the action of insulin and mediating blood glucose reduction (page 37 lines 18-23).
Reaume teach that insulin signals the liver to stop making sugars (sections 0116-0117). Reaume teach the invention provides methods to increase insulin sensitivity by administering compounds as claimed (section 0105). Thus, the prior art suggest that the claimed compounds can increase insulin sensitivity which appears to be what is presented in applicants’ example 3. Since the prior art suggest such effect it is unclear why such outcome is deemed unexpected. As noted above, MPEP 716.01(a) expressly teach that a greater than additive effect can be expected. In the instant case, Reaume teach that insulin signals the liver to stop making sugars (sections 0116-0117). Reaume teach the invention provides methods to increase insulin sensitivity by administering compounds as claimed (section 0105). Thus, insulin alone is known to have an effect of blood glucose. Further, the claimed compounds are suggested as increasing insulin sensitivity. By expressly suggesting an INCREASE in insulin sensitivity the prior art suggests that the compounds increase the effect (i.e. reducing sugar levels). Thus, the teachings of the reference suggest an increased (greater than insulin alone) effect.
Further, Reaume teach that the compounds direct the modulation of lyn kinase in the insulin receptor pathway and lyn activation has insulin receptor activation like activity (sections 0006, 0032 and 0091 and figure 12). Reaume specifically teach the compounds up-regulate the expression and/or activity of lyn kinase (section 0059). Reaume teach the methods for reducing blood glucose levels (section 0008). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). Reaume teach that insulin signals the liver to stop making sugars (sections 0116-0117). Thus, there is no reasonable basis to conclude that the results are unexpected because Reaume has set forth an expectation of how the compounds work and directly links the functionality to insulin activity (instant claim 49 expressly states that the mammal produces no insulin). Thus based on the teachings of Reaume there is no adequate basis to conclude that the results are unexpected.
MPEP 716.02(d) states that unexpected results are to be commensurate in scope with the claimed invention. Instant claim 49 refers to a generic structure of formula I and claims 49 and 60 refer to a generic class of insulin. The examples appear to relate to a single compound of formula I and a single insulin (although it is not immediately evident what type of insulin was tested).
Further, MPEP 716.02(c) states that expected beneficial results are evidence of obviousness. Instant figure 3 relates to effects on blood glucose. Figures 1 and 2 of Reaume show that compound 102 can reduce blood glucose. Reaume teach the methods for reducing blood glucose levels (section 0008). Further, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume et al. (US 2010/0152215; ‘Reaume2010’; first cited 6/21/24) shows the synergy of compound 102 (also known as MLR-1023) with another compound with respect to blood glucose levels (figure 1 and section 0023). Reaume teach that the compounds direct the modulation of lyn kinase in the insulin receptor pathway and lyn activation has insulin receptor activation like activity (sections 0006, 0032 and 0091 and figure 12). Reaume specifically teach the compounds up-regulate the expression and/or activity of lyn kinase (section 0059). Based on the totality of evidence of record there is no reasonable basis to conclude unexpected results commensurate in scope with the claims.
Although applicants argue about figure 3 and the combination of insulin and compound 102 having a different blood glucose response, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Figure 3B shows that insulin alone reduces blood glucose. One reasonable interpretation of figure 3B is that compound 102 increases insulin sensitivity. Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Thus, the data appears to confirm the teachings and suggestions of Reaume. Although applicants refer to a ‘different’ blood glucose response for the combination, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105) which suggests that one would have expected a non-identical response.
Although applicants argue about US 2010/0152215, the 103 rejection is set forth above. The teachings of Reaume et al. (US 2007/0093516; ‘Reaume’; cited with IDS 4/2/20) are discussed in detail above. Applicants have not set forth any position on Reaume express teaching that the invention provides methods to increase insulin sensitivity (section 0105) and based on such teaching the expected effect of compound 102 on insulin. MPEP 716.02(c) states that expected beneficial results are evidence of obviousness. Since applicants have made arguments related to unexpected results, the examiner has cited evidence as to the nature of what was known in the art (extrinsic evidence). With respect to the arguments about teaching an identical combination, there is no 102 rejection of record.
Although applicants argue that Reaume2010 contradicts the clear meaning of terms in the claim, applicants have not pointed to any specific term in the claim as being contradicted.
Although applicants argue that figure 3 provides a contrast to Reaume who teach effects can be lost at 90 minutes in example 1, it is important to note that example 1 of Reaume (page 14) does not include administration of insulin and Reaume is not limited to a specific dose under specific conditions. Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Without additional insulin administration one would not necessarily have expected additional effects. Further, a different example of Reaume (example 4 and figure 9) shows that specific doses of compound 102 reduced blood glucose levels (section 0179 and figure 9). Reaume teach that the blood glucose levels were measured 2 hours (120 minutes) after the injection (section 0177). Thus, Reaume does teach that the effects of compound 102 can be present at 2 hours (120 minutes).
Although applicants argue that Reaume does not affirm synergistic results, the instant rejection is a 103 rejection not a 102 rejection. As such, Reaume does not necessarily anticipate the claims. As discussed in detail above (emphasis added): MPEP 716.02(a) recognizes that a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such effect can either be expected or unexpected. There is no requirement that the basis of expectation be an anticipatory reference.
Double Patenting
Claims were previously rejected based on the patents/application/references cited below. Since the claims have been amended the rejections are updated to correspond to the instant claim.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 49-58 and 60-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12,011,445 (445) in view of Cnop et al. (‘Mechanisms of pancreatic beta cell death in type 1 and type 2 diabetes’ Diabetes v54 supplement 2 December 2005 pages s97-sl07; ‘Cnop’; cited with IDS 4/2/20) in view of Reaume et al. (US 2007/0093516; ‘Reaume’; cited with IDS 4/2/20) in view of Raj et al. (‘Oral Insulin – A Perspective’ Journal of Biomaterials Applications v17 Jan 2003 pages 183-196; cited with IDS 4/2/20; ‘Raj’) in view of DeWitt et al. (‘Outpatient insulin therapy in type 1 and type 2 diabetes mellitus’ JAMA v289(17) May 7 2003 pages 2254-2264 and pages e1-e7 for a total of 18 pages; ‘DeWitt’; cited with IDS 4/2/20).
445 recite administering compounds to humans in need thereof for treating pancreatic beta cell degeneration (claim 1).
4455 does not explicitly recite type 1 diabetes in the claims.
Cnop teach that type 1 diabetes is characterized by beta cell failure (abstract).
Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Reaume specifically teach methods for reducing blood glucose levels (section 0008). Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014). Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Reaume teach that the compounds of the invention direct the modulation of lyn kinase in the insulin receptor pathway (section 0006). Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach the inclusion of a fibrate with the composition (section 0143).
Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Raj teach that diabetes mellitus can be controlled quite well with insulin injections (page 185 2nd complete paragraph).
DeWitt teach insulin therapies for type 1 diabetes (title). In the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3). As shown in figure 1a, the long-acting insulin glargine is known to be administered. DeWitt teach advantages of using glargine (page 2254 section data synthesis) and also recognize the use of other insulin products (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of 445 to use specific mammals in need thereof. 445 recites treating pancreatic beta cell degeneration thus one would be motivated to treat mammals in need thereof as claimed including those with type 1 diabetes as taught by Cnop, Reaume, Raj and DeWitt using the known methods taught by the references because Cnop teach that type 1 diabetes is characterized by beta cell failure (abstract). Thus based on the nature of the problem to be solved and suggestion of 445 to treat pancreatic beta cell degeneration one would be motivated to administer appropriate compounds. Since Reaume teach the inclusion of a fibrate with the composition (section 0143) one would have been motivated to do such. One would have had a reasonable expectation of success since 445 recite the administration for a particular purpose. Reaume expressly teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) and in the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3).
In relation to the patient population as recited in claims 49, 53 and 60, Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Thus, one would have been motivated to administer to those with diabetes, specifically those who produce no insulin. Further, DeWitt teach insulin therapies for type 1 diabetes (title).
In relation to the insulin as recited in claims 49, 55-57 and 60, DeWitt teach using glargine (page 2254 section data synthesis) which is long acting (table 1) and also recognize the use of other insulin products including rapid and short acting (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption). DeWitt teach once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3) and the use of intravenous injection of insulin (page 225 last complete paragraph) thus suggesting bolus injection.
In relation to the compound of formula I as recited in claims 49-52, 54, 58 and 60, Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). As shown in section 0088 of Reaume compound 102 is applicants’ elected species and meets the structural requirements as claimed. Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014).
In relation to the sequential administration as in claims 49 and 60, Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Further, since Reaume specifically teach methods for reducing blood glucose levels (section 0008) one would be motivated to optimize the timing to achieve such goal (MPEP 2144.05 IIB). DeWitt teach that the peak of the insulin product can be as little as 30-90 minutes (Table 1).
In relation to claim 61, Reaume teach the inclusion of a fibrate with the composition (section 0143).
In relation to the outcomes recited in the last 3 lines of claim 49 and the last 4 lines of claim 60 and the intended uses of the first 3 lines of claim 49 and 60, the prior art suggest the agents as claimed so they would function as claimed. Further, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach that the compounds direct the modulation of lyn kinase in the insulin receptor pathway and lyn activation has insulin receptor activation like activity (sections 0006, 0032 and 0091 and figure 12). Reaume specifically teach the compounds up-regulate the expression and/or activity of lyn kinase (section 0059). Further, Reaume (example 4 and figure 9) shows that specific doses of compound 102 reduced blood glucose levels (section 0179 and figure 9) and teach that the blood glucose levels were measured 2 hours (120 minutes) after the injection (section 0177).
Claims 49-58 and 60-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 92-107 of copending Application No. 18/619,938 (938) in view of Cnop et al. (‘Mechanisms of pancreatic beta cell death in type 1 and type 2 diabetes’ Diabetes v54 supplement 2 December 2005 pages s97-sl07; ‘Cnop’; cited with IDS 4/2/20) in view of Reaume et al. (US 2007/0093516; ‘Reaume’; cited with IDS 4/2/20) in view of Raj et al. (‘Oral Insulin – A Perspective’ Journal of Biomaterials Applications v17 Jan 2003 pages 183-196; cited with IDS 4/2/20; ‘Raj’) in view of DeWitt et al. (‘Outpatient insulin therapy in type 1 and type 2 diabetes mellitus’ JAMA v289(17) May 7 2003 pages 2254-2264 and pages e1-e7 for a total of 18 pages; ‘DeWitt’; cited with IDS 4/2/20).
This is a provisional nonstatutory double patenting rejection.
938 recite administering compounds to mammals in need thereof for treating pancreatic beta cell degeneration (claims 92 and 102).
938 does not explicitly recite type 1 diabetes in the claims.
Cnop teach that type 1 diabetes is characterized by beta cell failure (abstract).
Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Reaume specifically teach methods for reducing blood glucose levels (section 0008). Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014). Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Reaume teach that the compounds of the invention direct the modulation of lyn kinase in the insulin receptor pathway (section 0006). Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach the inclusion of a fibrate with the composition (section 0143).
Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Raj teach that diabetes mellitus can be controlled quite well with insulin injections (page 185 2nd complete paragraph).
DeWitt teach insulin therapies for type 1 diabetes (title). In the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3). As shown in figure 1a, the long-acting insulin glargine is known to be administered. DeWitt teach advantages of using glargine (page 2254 section data synthesis) and also recognize the use of other insulin products (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of 938 to use specific mammals in need thereof. 938 recites treating pancreatic beta cell degeneration thus one would be motivated to treat mammals in need thereof as claimed including those with type 1 diabetes as taught by Cnop, Reaume, Raj and DeWitt using the known methods taught by the references because Cnop teach that type 1 diabetes is characterized by beta cell failure (abstract). Thus based on the nature of the problem to be solved and suggestion of 595 to treat pancreatic beta cell degeneration one would be motivated to administer appropriate compounds. Since Reaume teach the inclusion of a fibrate with the composition (section 0143) one would have been motivated to do such. One would have had a reasonable expectation of success since 595 recite the administration for a particular purpose. Reaume expressly teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) and in the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3).
In relation to the patient population as recited in claims 49, 53 and 60, Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Thus, one would have been motivated to administer to those with diabetes, specifically those who produce no insulin. Further, DeWitt teach insulin therapies for type 1 diabetes (title).
In relation to the insulin as recited in claims 49, 55-57 and 60, DeWitt teach using glargine (page 2254 section data synthesis) which is long acting (table 1) and also recognize the use of other insulin products including rapid and short acting (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption). DeWitt teach once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3) and the use of intravenous injection of insulin (page 225 last complete paragraph) thus suggesting bolus injection.
In relation to the compound of formula I as recited in claims 49-52, 54, 58 and 60, Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). As shown in section 0088 of Reaume compound 102 is applicants’ elected species and meets the structural requirements as claimed. Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014).
In relation to the sequential administration as in claims 49 and 60, Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Further, since Reaume specifically teach methods for reducing blood glucose levels (section 0008) one would be motivated to optimize the timing to achieve such goal (MPEP 2144.05 IIB). DeWitt teach that the peak of the insulin product can be as little as 30-90 minutes (Table 1).
In relation to claim 61, Reaume teach the inclusion of a fibrate with the composition (section 0143).
In relation to the outcomes recited in the last 3 lines of claim 49 and the last 4 lines of claim 60 and the intended uses of the first 3 lines of claim 49 and 60, the prior art suggest the agents as claimed so they would function as claimed. Further, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach that the compounds direct the modulation of lyn kinase in the insulin receptor pathway and lyn activation has insulin receptor activation like activity (sections 0006, 0032 and 0091 and figure 12). Reaume specifically teach the compounds up-regulate the expression and/or activity of lyn kinase (section 0059). Further, Reaume (example 4 and figure 9) shows that specific doses of compound 102 reduced blood glucose levels (section 0179 and figure 9) and teach that the blood glucose levels were measured 2 hours (120 minutes) after the injection (section 0177).
Claims 49-58 and 60-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,251,883 (883) in view of Reaume et al. (US 2007/0093516; ‘Reaume’; cited with IDS 4/2/20) in view of Raj et al. (‘Oral Insulin – A Perspective’ Journal of Biomaterials Applications v17 Jan 2003 pages 183-196; cited with IDS 4/2/20; ‘Raj’) in view of DeWitt et al. (‘Outpatient insulin therapy in type 1 and type 2 diabetes mellitus’ JAMA v289(17) May 7 2003 pages 2254-2264 and pages e1-e7 for a total of 18 pages; ‘DeWitt’; cited with IDS 4/2/20).
883 recite treating insulin dependent diabetes mellitus in a mammal comprising administering a particular compound (claim 1) where insulin is also administered (claims 16-17). 883 also recites fibrates including fenofibrate (claim 15).
883 does not further describe those with insulin dependent diabetes mellitus or recite specific insulin types.
Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Reaume specifically teach methods for reducing blood glucose levels (section 0008). Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014). Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Reaume teach that the compounds of the invention direct the modulation of lyn kinase in the insulin receptor pathway (section 0006). Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach the inclusion of a fibrate with the composition (section 0143).
Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Raj teach that diabetes mellitus can be controlled quite well with insulin injections (page 185 2nd complete paragraph).
DeWitt teach insulin therapies for type 1 diabetes (title). DeWitt teach the use of intravenous injection of insulin (page 225 last complete paragraph). In the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3). As shown in figure 1a, the long-acting insulin glargine is known to be administered. DeWitt teach advantages of using glargine (page 2254 section data synthesis) and also recognize the use of other insulin products (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of 883 to use specific mammals in need thereof. One would be motivated to treat mammals in need thereof as claimed including those with type 1 diabetes as taught by Reaume, Raj and DeWitt using the known methods taught by the references. Thus based on the nature of the problem to be solved one would be motivated to administer appropriate compounds based on the specific suggestions of 883. Since 883 (claim 15) and Reaume (section 0143) suggest the inclusion of a fibrate one would have been motivated to do such. One would have had a reasonable expectation of success since 883 recite the administration for a particular purpose (claim 1). Reaume expressly teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) and in the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3).
In relation to the patient population as recited in claims 49, 53 and 60, Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Thus, one would have been motivated to administer to those with diabetes, specifically those who produce no insulin. Further, DeWitt teach insulin therapies for type 1 diabetes (title).
In relation to the insulin as recited in claims 49, 55-57 and 60, DeWitt teach using glargine (page 2254 section data synthesis) which is long acting (table 1) and also recognize the use of other insulin products including rapid and short acting (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption). DeWitt teach once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3) and the use of intravenous injection of insulin (page 225 last complete paragraph) thus suggesting bolus injection.
In relation to the compound of formula I as recited in claims 49-52, 54, 58 and 60, Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). As shown in section 0088 of Reaume compound 102 is applicants elected species and meets the structural requirements as claimed. Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014).
In relation to the sequential administration as in claims 49 and 60, Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Further, since Reaume specifically teach methods for reducing blood glucose levels (section 0008) one would be motivated to optimize the timing to achieve such goal (MPEP 2144.05 IIB). DeWitt teach that the peak of the insulin product can be as little as 30-90 minutes (Table 1).
In relation to claim 61, 883 (claim 15) and Reaume (section 0143) suggest the inclusion of a fibrate.
In relation to the outcomes recited in the last 3 lines of claim 49 and the last 4 lines of claim 60 and the intended uses of the first 3 lines of claim 49 and 60, the prior art suggest the agents as claimed so they would function as claimed. Further, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach that the compounds direct the modulation of lyn kinase in the insulin receptor pathway and lyn activation has insulin receptor activation like activity (sections 0006, 0032 and 0091 and figure 12). Reaume specifically teach the compounds up-regulate the expression and/or activity of lyn kinase (section 0059). Further, Reaume (example 4 and figure 9) shows that specific doses of compound 102 reduced blood glucose levels (section 0179 and figure 9) and teach that the blood glucose levels were measured 2 hours (120 minutes) after the injection (section 0177).
Claims 49-58 and 60-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,786,503 (503) in view of Reaume et al. (US 2007/0093516; ‘Reaume’; cited with IDS 4/2/20) in view of Raj et al. (‘Oral Insulin – A Perspective’ Journal of Biomaterials Applications v17 Jan 2003 pages 183-196; cited with IDS 4/2/20; ‘Raj’) in view of DeWitt et al. (‘Outpatient insulin therapy in type 1 and type 2 diabetes mellitus’ JAMA v289(17) May 7 2003 pages 2254-2264 and pages e1-e7 for a total of 18 pages; ‘DeWitt’; cited with IDS 4/2/20).
503 recite treating type 1 diabetes in a mammal comprising administering a particular compound (claim 2).
503 does not further describe those with type 1 diabetes mellitus nor does 503 recite the administration of insulin.
Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Reaume specifically teach methods for reducing blood glucose levels (section 0008). Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014). Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Reaume teach that the compounds of the invention direct the modulation of lyn kinase in the insulin receptor pathway (section 0006). Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach the inclusion of a fibrate with the composition (section 0143).
Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Raj teach that diabetes mellitus can be controlled quite well with insulin injections (page 185 2nd complete paragraph).
DeWitt teach insulin therapies for type 1 diabetes (title). DeWitt teach the use of intravenous injection of insulin (page 225 last complete paragraph). In the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3). As shown in figure 1a, the long-acting insulin glargine is known to be administered. DeWitt teach advantages of using glargine (page 2254 section data synthesis) and also recognize the use of other insulin products (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of 503 to use specific mammals in need thereof and to use insulin based on the suggestion of 503 and because DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3). Thus one would be motivated to treat mammals in need thereof as claimed including those with type 1 diabetes as taught by Reaume, Raj and DeWitt using the known methods taught by the references. Thus based on the nature of the problem to be solved one would be motivated to administer appropriate compounds. Since Reaume teach the inclusion of a fibrate with the composition (section 0143) one would have been motivated to do such. One would have had a reasonable expectation of success since 503 recite the administration for a particular purpose (claim 2). Reaume expressly teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) and in the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3).
In relation to the patient population as recited in claims 49, 53 and 60, Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Thus, one would have been motivated to administer to those with diabetes, specifically those who produce no insulin. Further, DeWitt teach insulin therapies for type 1 diabetes (title).
In relation to the insulin as recited in claims 49, 55-57 and 60, DeWitt teach using glargine (page 2254 section data synthesis) which is long acting (table 1) and also recognize the use of other insulin products including rapid and short acting (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption). DeWitt teach once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3) and the use of intravenous injection of insulin (page 225 last complete paragraph) thus suggesting bolus injection.
In relation to the compound of formula I as recited in claims 49-52, 54, 58 and 60, Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). As shown in section 0088 of Reaume compound 102 is applicants elected species and meets the structural requirements as claimed. Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014).
In relation to the sequential administration as in claims 49 and 60, Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Further, since Reaume specifically teach methods for reducing blood glucose levels (section 0008) one would be motivated to optimize the timing to achieve such goal (MPEP 2144.05 IIB). DeWitt teach that the peak of the insulin product can be as little as 30-90 minutes (Table 1).
In relation to claim 61, Reaume teach the inclusion of a fibrate with the composition (section 0143).
In relation to the outcomes recited in the last 3 lines of claim 49 and the last 4 lines of claim 60 and the intended uses of the first 3 lines of claim 49 and 60, the prior art suggest the agents as claimed so they would function as claimed. Further, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach that the compounds direct the modulation of lyn kinase in the insulin receptor pathway and lyn activation has insulin receptor activation like activity (sections 0006, 0032 and 0091 and figure 12). Reaume specifically teach the compounds up-regulate the expression and/or activity of lyn kinase (section 0059). Further, Reaume (example 4 and figure 9) shows that specific doses of compound 102 reduced blood glucose levels (section 0179 and figure 9) and teach that the blood glucose levels were measured 2 hours (120 minutes) after the injection (section 0177).
Claims 49-58 and 60-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,534,442 (442) in view of Reaume et al. (US 2007/0093516; ‘Reaume’; cited with IDS 4/2/20) in view of Raj et al. (‘Oral Insulin – A Perspective’ Journal of Biomaterials Applications v17 Jan 2003 pages 183-196; cited with IDS 4/2/20; ‘Raj’) in view of DeWitt et al. (‘Outpatient insulin therapy in type 1 and type 2 diabetes mellitus’ JAMA v289(17) May 7 2003 pages 2254-2264 and pages e1-e7 for a total of 18 pages; ‘DeWitt’; cited with IDS 4/2/20).
442 recite treating type 1 diabetes in a mammal comprising administering a particular compound (claim 1).
442 does not further describe those with type 1 diabetes mellitus nor does 442 recite the administration of insulin.
Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Reaume specifically teach methods for reducing blood glucose levels (section 0008). Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014). Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Reaume teach that the compounds of the invention direct the modulation of lyn kinase in the insulin receptor pathway (section 0006). Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach the inclusion of a fibrate with the composition (section 0143).
Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Raj teach that diabetes mellitus can be controlled quite well with insulin injections (page 185 2nd complete paragraph).
DeWitt teach insulin therapies for type 1 diabetes (title). DeWitt teach the use of intravenous injection of insulin (page 225 last complete paragraph). In the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3). As shown in figure 1a, the long-acting insulin glargine is known to be administered. DeWitt teach advantages of using glargine (page 2254 section data synthesis) and also recognize the use of other insulin products (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of 442 to use specific mammals in need thereof and to use insulin based on the suggestion of 442 and because DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3). Thus one would be motivated to treat mammals in need thereof as claimed including those with type 1 diabetes as taught by Reaume, Raj and DeWitt using the known methods taught by the references. Thus based on the nature of the problem to be solved one would be motivated to administer appropriate compounds. Since Reaume teach the inclusion of a fibrate with the composition (section 0143) one would have been motivated to do such. One would have had a reasonable expectation of success since 447 recite the administration for a particular purpose (claim 28). Reaume expressly teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) and in the section about the best regimens for type 1 diabetes, DeWitt teach that particular patients with type 1 diabetes do well receiving once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3).
In relation to the patient population as recited in claims 49, 53 and 60, Reaume teach compositions and methods for treating a glucose metabolism disorder where the disorder is insulin dependent diabetes mellitus (sections 0103-0104) in mammals specifically humans (sections 0007 and 0014). Raj teach that insulin dependent diabetes (IDDM) is type 1 diabetes and that type 1 diabetes develops when the immune system of the body destroys pancreatic beta cells the only cells that make insulin (page 184 2nd paragraph). Raj teach that in type I diabetes beta-cells eventually produce no insulin at all (page 186 first complete paragraph) and that insulin therapy is necessary for IDDM (page 186 last paragraph). Thus, one would have been motivated to administer to those with diabetes, specifically those who produce no insulin. Further, DeWitt teach insulin therapies for type 1 diabetes (title).
In relation to the insulin as recited in claims 49, 55-57 and 60, DeWitt teach using glargine (page 2254 section data synthesis) which is long acting (table 1) and also recognize the use of other insulin products including rapid and short acting (Table 1 on page 2255 and page 2259). With respect to the amounts, DeWitt teach that injections are typically 0.1-0.2 U/kg (Table 1 caption). DeWitt teach once daily insulin injections (page 2258 2nd-3rd column and figures 1 and 3) and the use of intravenous injection of insulin (page 225 last complete paragraph) thus suggesting bolus injection.
In relation to the compound of formula I as recited in claims 49-52, 54, 58 and 60, Reaume teach that the compound used in the composition can be of a particular structure where the compound administered orally reduced blood glucose levels (section 0018, section 0088 compound 102 and example 6.5.1 of page 15). As shown in section 0088 of Reaume compound 102 is applicants elected species and meets the structural requirements as claimed. Reaume teach that an effective amount is about 0.1 mg to about 100 mg/kg that is administered orally (section 0014).
In relation to the sequential administration as in claims 49 and 60, Reaume teach that the agent is administered subsequent to the administration of another agent (section 0141) where the other agent is insulin (section 0148). Further, since Reaume specifically teach methods for reducing blood glucose levels (section 0008) one would be motivated to optimize the timing to achieve such goal (MPEP 2144.05 IIB). DeWitt teach that the peak of the insulin product can be as little as 30-90 minutes (Table 1).
In relation to claim 61, Reaume teach the inclusion of a fibrate with the composition (section 0143).
In relation to the outcomes recited in the last 3 lines of claim 49 and the last 4 lines of claim 60 and the intended uses of the first 3 lines of claim 49 and 60, the prior art suggest the agents as claimed so they would function as claimed. Further, Reaume teach the invention provides methods to increase insulin sensitivity (section 0105). Reaume teach the compound of the invention and the therapeutic agent can act synergistically (section 0141). Reaume teach that the compounds direct the modulation of lyn kinase in the insulin receptor pathway and lyn activation has insulin receptor activation like activity (sections 0006, 0032 and 0091 and figure 12). Reaume specifically teach the compounds up-regulate the expression and/or activity of lyn kinase (section 0059). Further, Reaume (example 4 and figure 9) shows that specific doses of compound 102 reduced blood glucose levels (section 0179 and figure 9) and teach that the blood glucose levels were measured 2 hours (120 minutes) after the injection (section 0177).
Response to Arguments – double patenting
Applicant's arguments filed 1/6/26 have been fully considered but they are not persuasive with respect to the rejections set forth above.
Although applicants argue about the deficiencies of references and arguments previously made of record and arguments about synergy, such arguments are addressed above and/or previously and are not found persuasive.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658
Prosecution Insights