DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendments and remarks filed on 12/29/2025 have been fully considered.
Claims 1, 4-11, 22, and 35 are pending for examination. Claims 2-3, 12-21, 23-34 and 36-53 are cancelled.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4-10, 22, and 35 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims that depend directly or indirectly from claim 1 is/are also rejected due to said dependency. In regard to claims 1, 22 and 35, the claims recite “(determining) the subject's blood glucose concentration, wherein the subject's blood glucose is measured continuously”. It is unclear whether “the subject's blood glucose” refers to the subject’s “blood glucose concentration” or other glucose measurement(s). Clarification is requested by amendments.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 4-6, 8-9, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. “OGTT 1h serum C-peptide to plasma glucose concentration ratio is more related to beta cell function and diabetes mellitus. Oncotarget, Vol. 8, No. 31, pp. 51786-51791 (2017) - applicant cited, in view of Sekimoto et al. (USPGPUB 2012/027/1557) and further in view of McCamish (USPGPUB 2008/0280955 – applicant cited). In regard to claim 1, Zhang discloses a method of identifying a subject with insulin resistance (Pg. 51787, Col. 1, Para. 3, 1021 patients were non-diabetic and aged 27 to 80 years old. They all underwent a 75-g oral glucose tolerance test (OGTT) to determine whether they were suffering from diabetes according to WHO 1999 diagnostic criteria; Pg. 51788, Col. 1, Para. 2, of all the 1021 studied subjects, 324 were diagnosed with diabetes after OGTT according to WHO 1999 diagnostic criteria; Pg. 51786, Col. 1, Para. 1, Progressive pancreatic β-cell function failure and insulin resistance are the key characteristics of type 2 diabetes mellitus (T2DM)), the method comprising: determining the subject's blood glucose concentration (Pg. 51787, Col. 1, Para. 4, Blood samples were drawn at 0, 30, 60, 120 and 180 min after the glucose load to determine glucose concentrations; Pg. 51787, Col. 2, Para. 2, Plasma glucose was measured by enzymatic hexokinase hotometric assay), determining the subject's blood or urinary C-peptide level (Pg. 51787, Col. 1, Para. 4, Blood samples were drawn at 0, 30, 60, 120 and 180 min after the glucose load to determine ... C-peptide levels; Pg. 51787, Col. 2, Para. 2, C-peptide was determined by Luminescent immunoassays); calculating the ratio of the subject's blood glucose concentration to the blood or urinary C-peptide concentration (Pg. 51787, Col. 2, Para. 3, CPI was calculated as: 100 x serum C-peptide level (ng/mL)/ plasma glucose level (mg/dL); it is noted that A/B and B/A are inverse correlated; it is interpreted according to paragraph [0135] of the specification of the PGPUB of current application, which indicates “24 h C-peptide urinary levels/24 h circulating glucose ratio”, paragraphs [0222] and [0224] indicate “24 urinary C-peptide/24 h serum glucose levels ratio”; and paragraph [0072] indicates possible ratio ranges ); identifying a subject with insulin resistance if this ratio is high; or identifying a subject with normal insulin sensitivity if this ratio is low (Pg. 51788, Col. 1, Para. 2, Of all the 1021 studied subjects, 324 were diagnosed with diabetes after OGTT according to WHO 1999 diagnostic criteria; Pg. 51786, Col. 1, Para. 1, Progressive pancreatic β-cell function failure and insulin resistance are the key characteristics of type 2 diabetes mellitus (T2DM); Pg. 51789, Col. 1, Para. 3, CPI 1 h has the highest diagnostic value to predict diabetes mellitus (AROC = 0.937, sensitivity = 90%, specificy = 85.2%); see also Fig. 1, Blood glucose and serum C-peptide levels in DM and non-DM group).
Zhang does not specifically disclose the subject's blood glucose is measured continuously.
Sekimoto teaches a CGM measuring apparatus for performing the continuous blood sugar measurement (Figs. 1-3, 15-22, 24-26, and 28-31 and associated descriptions) comprising measuring the subject's blood glucose continuously (rejected as best understood, see the 35 USC 112(b) rejection above; before, during and after an OGTT measurement: in the case of the CGM measuring apparatus, a glucose sensor is retained subcutaneously over a span of about several days to several weeks to continuously measure the blood sugar level, [0007] and [0108]; continuously measure during an OGTT measurement period, Figs. 27-30 and associated descriptions; [0208-0214]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method (Zhang) to incorporate the CGM and associated elements/functions/steps as taught by Sekimoto, since both methods are OGTT related glucose measurements and one of ordinary skill in the art would have recognized that in addition to or alternatively for the blood sampling periods during the OGTT, glucose information can be monitored continuously before, during and/or after the OGTT (see Sekimoto). The rationale would have been to obtain more glucose information before, during and/or after the OGTT.
Zhang as modified by Sekimoto does not specifically disclose treating the subject.
McCamish is also in the field of methods of screening for insulin resistance (Abstract) and teaches treating the subject ([0017], methods of screening and treatment of an individual suffering from a disorder of blood glucose regulation, e.g., an insulin resistance disorder; [0004], methods can also further include administering or not administering an insulin sensitizer to the individual based on the results of the screening of the individual).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method (Zhang as modified by Sekimoto) to incorporate treating the subject with associated treating steps as taught by McCamish. The rationale would have been to encourage insulin production in a subject and thereby affect therapeutic benefit in the subject having a metabolic disorder ([0030]).
In regard to claim 4, Zhang as modified by Sekimoto and McCamish discloses the blood glucose concentration is continuously measured over a period of time (Pg. 51787, Col. 1, Para. 4, Blood samples were drawn at 0, 30, 60, 120 and 180 min after the glucose load to determine glucose concentrations; Pg. 51787, Col. 2, Para. 2, Plasma glucose was measured by enzymatic hexokinase hotometric assay of Zhang; continuously measured during OGTT, Figs. 27-31 and associated descriptions of Sekimoto; referring to claim 1 above).
In regard to claim 5, Zhang as modified by Sekimoto and McCamish discloses the period of time comprises about 24 hours (referring to claim 1 above; days to several weeks; [0007] and [0108] of Sekimoto).
In regard to claim 6, Zhang as modified by Sekimoto and McCamish discloses the subject’s blood or urinary C-peptide level is measured over a period of time (Pg. 51787, Col. 1, Para. 4, Blood samples were drawn at 0, 30, 60, 120 and 180 min after the glucose load to determine ... C-peptide levels; Pg. 51787, Col. 2, Para. 2, C-peptide was determined by Luminescent immunoassays of Zhang).
In regard to claim 8, Zhang as modified by Sekimoto and McCamish discloses the blood glucose concentration and the urinary C-peptide level are measured simultaneously or sequentially (Pg. 51787, Col. 1, Para. 4, Blood samples were drawn at 0, 30, 60, 120 and 180 min after the glucose load to determine glucose concentrations, serum insulin levels, C-peptide levels of Zhang).
In regard to claim 9, Zhang as modified by Sekimoto and McCamish discloses the subject's blood glucose concentration is measured using a transcutaneous glucose monitor (CGM) (referring to claim 1 above).
In regard to claim 22, Zhang as modified by Sekimoto and McCamish discloses a method of identifying a subject with or at risk of a disease characterized by insulin resistance (referring to claim 1 above), the method comprising: determining the subject's blood glucose concentration (referring to claim 1 above), wherein the subject’s blood glucose is measured continuously (rejected as best understood, see the 35 USC 112(b) rejection above; referring to claim 1 above) determining the subject's blood or urinary C-peptide level (referring to claim 1 above), calculating a ratio of the subject's blood glucose concentration to the subject's blood or urinary C-peptide level (referring to claim 1 above), thereby identifying a subject with or at risk of a disease characterized by insulin resistance if the ratio is high (referring to claim 1 above), and treating the subject (referring to claim 1 above).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Zhang, Sekimoto and McCamish as applied to claims 1, 4-6, 8-9, and 22 above, and further in view of Saisho et al. “Postprandial serum C-peptide to plasma glucose ratio as a predictor of subsequent insulin treatment in patients with type 2 diabetes”. Endocrine Journal, Vol. 58, No. 4, pp. 315-322 (2011) – applicant cited). In regard to claim 7, Zhang as modified by Sekimoto and McCamish discloses all the claimed limitation except the subject’s blood or urinary C-peptide level is measured over a period of time comprises about 24 hours.
Saisho is also in the field of methods of measuring C-peptide levels (Saisho, Abstract) and teaches wherein the period of time comprises about 24 hours (Saisho Pg. 316, Col. 2, Para. 3, … Urinary CPR index was calculated as 24 h urinary CPR (µg/day) / FPG (mg/dL)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method (Zhang as modified by Sekimoto and McCamish) to incorporate a period of time comprises about 24 hours as taught by Saisho. The motivation for doing so would have been to obtain more information in the subject (Saisho Pg. 316, Col. 2, Para. 3).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Zhang, Sekimoto and McCamish as applied to claims 1, 4-6, 8-9, and 22 above, and further in view of Kuniyuki (USPN5,089,419 - applicant cited). In regard to claim 10, Zhang as modified by Sekimoto and McCamish discloses all the claimed limitation except the subject's blood or urinary C-peptide level is measured using a transcutaneous monitor or a dipstick.
Kuniyuki is also in the field of methods of measuring C-peptide levels in a subject (Col. 1, lines 6-12) and teaches wherein the subject's blood or urinary C-peptide level is measured using a transcutaneous monitor or a dipstick (Col. 1, lines 10-11, detection and/or the qualitative measurement in urine of the presence of the connecting (or C) peptide; Col. 6, lines 34-37, the urine sample and C peptide-HRP conjugate are added in sequence following the same reaction time protocol. The dipstick incubations can be performed in a test tube).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method (Zhang as modified by Sekimoto and McCamish) to incorporate a dipstick as taught by Kuniyuki. The motivation for doing so would have been to provide a convenient product for use by the subject (Kuniyuki Col. 9, lines 51-57).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Kruszynska, and further in view of McCamish. In regard to claim 11, Kruszynska discloses a method of identifying a subject with insulin resistance (Pg. 104, Col. 1, Para. 2, To assess the relative contributions of insulin resistance and impaired insulin secretion to glucose intolerance, we also measured insulin sensitivity in these patients (29) and examined the relationships between insulin sensitivity, insulin secretion and glucose tolerance), the method comprising: determining the subject's blood or urinary C-peptide level (Pg. 104, Col. 2, Para. 3, Blood samples (10 ml) for glucose, insulin
and C-peptide estimation were taken at 15-min intervals until min 60 and then at 30-min intervals until min 180), normalizing the subject's blood or urinary C-peptide level for the subject's blood glucose concentration (Pg. 109, Col. 2, Para. 3, Because C-peptide levels were similar during this period, it would appear that the early hyperinsulinemia is essentially due to impaired insulin clearance. When the 3-hr insulin secretion rates after oral glucose were normalized for the differing blood glucose concentrations, identical values were obtained in cirrhotic patients and controls, suggesting that the increased insulin output after oral glucose intake in cirrhotic patients was a consequence
of the hyperglycemia), identifying the subject as having insulin resistance if the subject's normalized blood or urinary C-peptide level is above a threshold (Pg. 104, Col. 1, Para. 2, we used recombinant human C-peptide to measure C-peptide metabolic clearance rate in clinically stable cirrhotic patients, and applied the C-peptide kinetic data to the integrated peripheral C-peptide concentrations in the same individuals to calculate pancreatic insulin secretion rates ... To assess the relative contributions of insulin resistance and impaired insulin secretion to glucose intolerance, we also measured insulin sensitivity in these patients (29) and examined the relationships between insulin
sensitivity, insulin secretion and glucose tolerance; Pg. 109, Col. 1, Para. 2, Applying the C-peptide MCR to the calculation of insulin secretion rates, we found that in cirrhotic patients with normal fasting blood glucose concentrations, fasting C-peptide (and hence insulin) secretion rates were approximately double those of normal controls)
Kruszynska does not specifically disclose treating the subject.
McCamish is also in the field of methods of screening for insulin resistance ( Abstract) and teaches treating the subject ([0017], methods of screening and treatment of an individual suffering from a disorder of blood glucose regulation, e.g., an insulin resistance disorder; Para. [0004], methods can also further include administering or not administering an insulin sensitizer to the individual based on the results of the screening of the individual).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method (Kruszynska) to incorporate treating the subject as taught by McCamish. The motivation for doing so would have been to encourage insulin production in a subject and thereby affect therapeutic benefit in the subject having a metabolic disorder (McCamish Para. [0030]).
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Kruszynska et al. “Relationship between Insulin Sensitivity, Insulin Secretion and Glucose Tolerance in Cirrhosis”. Hepatology, Vol. 14, No 1, pp. 103-111 (1991) – applicant cited, in view of McCamish and further in view of Sekimoto. In regard to claim 11, Kruszynska discloses a method of identifying a subject with insulin resistance (Pg. 104, Col. 1, Para. 2, To assess the relative contributions of insulin resistance and impaired insulin secretion to glucose intolerance, we also measured insulin sensitivity in these patients (29) and examined the relationships between insulin sensitivity, insulin secretion and glucose tolerance), the method comprising: determining the subject's blood or urinary C-peptide level (Pg. 104, Col. 2, Para. 3, Blood samples (10 ml) for glucose, insulin and C-peptide estimation were taken at 15-min intervals until min 60 and then at 30-min intervals until min 180), normalizing the subject's blood or urinary C-peptide level for the subject's blood glucose concentration (Pg. 109, Col. 2, Para. 3, Because C-peptide levels were similar during this period, it would appear that the early hyperinsulinemia is essentially due to impaired insulin clearance. When the 3-hr insulin secretion rates after oral glucose were normalized for the differing blood glucose concentrations, identical values were obtained in cirrhotic patients and controls, suggesting that the increased insulin output after oral glucose intake in cirrhotic patients was a consequence of the hyperglycemia), identifying the subject as having insulin resistance if the subject's normalized blood or urinary C-peptide level is above a threshold (Pg. 104, Col. 1, Para. 2, we used recombinant human C-peptide to measure C-peptide metabolic clearance rate in clinically stable cirrhotic patients, and applied the C-peptide kinetic data to the integrated peripheral C-peptide concentrations in the same individuals to calculate pancreatic insulin secretion rates ... To assess the relative contributions of insulin resistance and impaired insulin secretion to glucose intolerance, we also measured insulin sensitivity in these patients (29) and examined the relationships between insulin sensitivity, insulin secretion and glucose tolerance; Pg. 109, Col. 1, Para. 2, Applying the C-peptide MCR to the calculation of insulin secretion rates, we found that in cirrhotic patients with normal fasting blood glucose concentrations, fasting C-peptide (and hence insulin) secretion rates were approximately double those of normal controls)
Kruszynska does not specifically disclose treating the subject.
McCamish is also in the field of methods of screening for insulin resistance ( Abstract) and teaches treating the subject ([0017], methods of screening and treatment of an individual suffering from a disorder of blood glucose regulation, e.g., an insulin resistance disorder; Para. [0004], methods can also further include administering or not administering an insulin sensitizer to the individual based on the results of the screening of the individual).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method (Kruszynska) to incorporate treating the subject as taught by McCamish. The motivation for doing so would have been to encourage insulin production in a subject and thereby affect therapeutic benefit in the subject having a metabolic disorder (McCamish Para. [0030]).
Kruszynska as modified by McCamish does not specifically disclose the subject's blood glucose is measured continuously.
Sekimoto teaches a CGM measuring apparatus for performing the continuous blood sugar measurement (Figs. 1-3, 15-22, 24-26, and 28-31 and associated descriptions) comprising measuring the subject's blood glucose continuously (rejected as best understood, see the 35 USC 112(b) rejection above; before, during and after an OGTT measurement: in the case of the CGM measuring apparatus, a glucose sensor is retained subcutaneously over a span of about several days to several weeks to continuously measure the blood sugar level, [0007] and [0108]; continuously measure during an OGTT measurement period, Figs. 27-30 and associated descriptions; [0208-0214]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method (Kruszynska as modified by McCamish) to incorporate the CGM and associated elements/functions/steps as taught by Sekimoto, since both methods are OGTT related glucose measurements and one of ordinary skill in the art would have recognized that CGM can provide continuous glucose measurements before, during and/or after the OGTT (see Sekimoto). The rationale would have been to obtain more glucose information before, during and/or after the OGTT.
Response to Arguments
Applicant’s arguments, see pages 5 and 6 of Remarks, filed on 12/29/2025, with respect to claim 48 have been fully considered and are persuasive. The 35 USC 101 and 102 rejections of claim 48 have been withdrawn.
Applicant’s arguments, see pages 5-6 of Remarks, filed on 12/29/2025, with respect to claims 1-10 and 48 have been fully considered and are persuasive. The 35 USC 112(b) rejections of claims 1-10 and 48 have been withdrawn.
Applicant’s amendment and argument with respect to claim 1 filed on 12/29/2025 have been fully considered but they are deemed to be moot in views of the new grounds of rejection.
It is noted that there is no amendments made for claim 11 and no argument is/are provided for claim 11. Therefore, the 35 USC 103 rejection of claim 11 is maintained for the reason of record.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CHU CHUAN LIU/ Primary Examiner, Art Unit 3791