DETAILED ACTION
Examiner acknowledges receipt of the reply filed 3/13/2026, in response to the restriction requirement mailed 2/12/2026.
Claims 1-21 and 44-45 are pending. Claims 3, 14-19, and 44-46 are withdrawn from further consideration for the reasons set forth below.
Claims 1, 2, 4-13, 20, and 21 are being examined on the merits in this office 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 .
Priority
The filing receipt dated 11/01/2023 provides the following information:
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Election/Restrictions
Applicant’s election applicants election of the following representative species is acknowledged:
type 2 diabetes
Claims 1, 2, 4-13, 20, and 21 read on the elected species.
Claims 3, 14-19, and 44-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/13/2026.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Claim Objections
Claims 1, 2, 4, 5, 8-10, 12, and 13 are objected to because of the following informalities:
Claim 1 should be amended to recite: “a) … for the subject; and b)”.
Claim 2 should be amended to only have a period at the end of the sentence. The claim should be amended to recite a)[[.]] … b)[[.]]…a fasting glucose c)[[.]].
Claim 4 should be amended to recite “the subject has TD2 and a FG > 120 mg/dL, and wherein the expected”.
Claim 5 should be amended to recite ““iv) … > 140 mg/dL; or b)”.
Claim 8 should be amended at lines 2-3 to recite “has either a baseline FG” and “iv) … > 140 mg/dL; or b)”.
Claim 9 should be amended “iv) … > 140 mg/dL; or b)”.
Claim 10 should be amended to recite “subject had a blood glucose episode”.
Claim 12 recites the acronym “MDI” which should be written in full name in the first order of appearance in the claims.
Claim 13 should be amended to recite
“b) iii)…10 units; or
iv) … 20 units; or
c) if the weekly . . .”
iii) … 20 units; or”.
Appropriate correction is required.
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, 2, 4-13, 20, and 21 are 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.
The metes and bounds of claim 1 are deemed to be indefinite. Claim 1 recites “expected weekly maintenance dose”. The specification states at p 8, ll. 17-19: The term "expected weekly maintenance dose," refers to the dose of insulin receptor agonist suitable for once-weekly dosing that would be expected to be needed to provide glycemic control in a given subject. This is a circular definition – the expected weekly maintenance dose is the dose to be expected for glycemic control. It is noted that the preamble of claim 1 recites a method of providing glycemic control. The claim and specification provide no meaningful guidance to the skilled artisan to ascertain what exactly is meant by the claim term. The specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claim clarification is required.
Because claims 2, 4-13, 20, and 21 depend from indefinite claim 1 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
Claim 2 recites the limitation “the subject's daily dose”. There is insufficient antecedent basis for this limitation in the claim.
Claim 5 recites the limitation "the previous week", “the previous dose”, and “the previous maintenance dose”. There is insufficient antecedent basis for this limitation in the claim.
Because claims 6, 7, 10-13, and 20 depend from indefinite claim 5 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
Claim 8 recites the limitation "the previous week", “the previous dose”, and “the previous maintenance dose”. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the previous week" and “the previous dose”. There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the need" and “the first 12 weeks”. There is insufficient antecedent basis for this limitation in the claim.
Claim 21 recites the limitation "the patient". There is insufficient antecedent basis for this limitation in the claim. Claim 21 depends from claim 1. Claim 1 provides antecedent support for a subject, but not a patient.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 21 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 21 depends from claim 1. The preamble of claim 1 recites “providing glycemic control”. Claim 21 recites “wherein the method comprises improving glycemic control in the patient”.
The as-filed specification states at p 28, ll 10-13:
“Glycemic control” refers to a subject's blood sugar levels, as measured for example by blood glucose and/or HbA1c levels; “providing” glycemic control refers to maintaining or improving glycemic control. Thus, providing is construed as meaning improving.
Accordingly, claim 21 is deemed to not further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 1, 2, 4-13, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Baldwin et al (U.S. 2016/0324932 – cited in IDS filed 3/14/2024), as evidenced by Clinical trial NCT03736785 (Version 12/02/2019 accessed at URL clinicaltrials.gov/study/NCT03736785?term=NCT03736785&viewType=Card&rank=1&tab=history&a=19#version-content-panel, pp. 1-15 (hereinafter referred to as “the clinical trial”)) and Church et al (EASD Virtual Mtg, Eur Assoc Study Diab 2018- cited in IDS filed 3/14/2024), further in view of Strange (J Diab Sci Tech 1:540-548 (2007)) and Frontoni et al (Diab Res Clin Pract 102:86-96 (2013)).
Baldwin et al disclose fusion proteins comprising an insulin receptor agonist fused to a human IgG Fc region through the use of a peptide linker, and the use of such fusion proteins in the treatment of diabetes. The fusion protein has an extended time action profile and is useful for providing basal glucose control for an extended period of time (abstract). The fusion proteins have prolonged duration of action compared to existing insulin treatments, allowing for less frequent injections than existing insulin products, including up to once weekly, thus reducing the complexity of and pain associated with existing treatment regimens involving more frequent injections. The fusion proteins have a flat pharmacokinetic profile and restricted peripheral exposure, resulting in low day-to-day variability, and minimal incidence of hypoglycemia (para. [0008]). The duration of action is sufficiently extended to allow for once weekly dosing (para. [0129]). The fusion proteins can be used to treat non-insulin dependent diabetes [type 2 diabetes] (e.g., para. [0128]). The phrase “therapeutically effective amount” refers to that amount of a fusion protein sufficient to regulate blood glucose in a patient without causing unacceptable side effects (e.g., paras. [0128]-[0129], [0135]). The skilled artisan will be able to determine appropriate dosages depending on the type and severity of the disease [type 2 diabetes] and on the characteristics of the subject, such as general health, age, sex, body weight, and tolerance to drugs. In certain embodiments, a therapeutically effective amount of an insulin-fc fusion protein administered once weekly ranges from about 0.01 nmol/kg to about 100 nmol/kg (e.g., paras. [0135]-[0138]). SEQ ID NO:12 correlates with insulin efistora alpha (LY3209590).
The clinical trial discloses a phase 2 trial assessing insulin-Fc (insulin efistora alpha/ formerly LY3209590) in patients with type 2 diabetes. The study was for patients previously treated with basal insulin, assessing changes from baseline in HbA1c, fasting glucose, change in body weight, and insulin dose over 32 weeks.
Church et al disclose administering a once weekly subcutaneous insulin-Fc fusion (10, 30, 60, or 90 nmol/kg) with continuous blood glucose monitoring over a week. Results indicate enhanced glucose control in both day and night. It’s up to 10 days following a single dose of insulin-fc. Continued repeat dosing of an insulin-fc every 10 days for 5 weeks demonstrated improved glycemic control. Church et al teach that current basal insulin therapy for type II diabetes supports daily dosing for patients with a focus on minimizing nocturnal hypoglycemia events. However, daily injections result in poor patient compliance. Church et al teaches that an insulin analog with a longer action time with less frequent administration could improve patient compliance and thus glycemic control.
Although Baldwin et al teach administering insulin efistora alpha to a type 2 diabetic subjects to provide glycemic control in the subject, the reference does not explicitly teach the recited dosing regimen.
Strange teaches dosing regimen containing insulin titration algorithms allow for type 2 diabetes patients to achieve targeted glucose levels. This is often referred to as Treat-to-target (pp. 541-542). Patient glucose levels are monitored (pp. 542-544). Insulin levels are adjusted accordingly to maintain target glucose levels and provide glycemic control in the diabetic patient (e.g., pp. 543-547). Examiner expressly notes that Strange is cited for the prior art knowledge/awareness and guidance of glucose monitoring of type II diabetic patients coupled with insulin dosage and titration to optimize glycemic control. The reference is not deemed to be limited to the specific insulin analogues disclosed in the reference.
Frontoni et al disclose that the most common forms of glucose monitoring involve self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) (p. 87, Table 1).
It would have been obvious to one of ordinary skill in the art to optimize result effective variables such as the amounts of initial loading dose and the maintenance dose of insulin efsitora alpha administered to a type II diabetic subject for providing glycemic control in the subject. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
The prior art taught that insulin efsitora alpha/ LY3209590 could be administered once a week for improving glycemic control in a subject with type 2 diabetes (Baldwin and the clinical trial). It was further known that an insulin-Fc analog could improve patient compliance and thus glycemic control (Church et al). Baldwin et al taught that the skilled artisan could determine appropriate insulin-fc dosages depending on the type and severity of the diabetes, and specific characteristics of the subject, e.g. age, sex, body weight, etc. Baldwin et al disclosed insulin-fc doses that could be administered weekly to a subject. Church also provided dosages that were determined to provide glycemic control in a type 2 diabetic animal model.
Strange disclosed dosing regimens/insulin titration algorithms that allowed for achieving and maintaining targeted glucose levels. Strange and Frontoni taught methods of assessing glucose levels, e.g. self-monitoring and continuous glucose monitoring. The assessed glucose levels provided information/data for the skilled artisan to titrate appropriate insulin-fc dosage amounts for subsequent once-weekly maintenance doses in order maintain targeted glucose levels in the subject.
Therefore, it would have been obvious to optimize the initial dose of insulin efistora alpha based on data obtained from glucose monitoring of the subject, as well as optimizing the dose amount needed in subsequent weekly maintenance dose(s) to achieve targeted glucose levels and maintain glycemic control in the subject. The skilled artisan would further have recognized that the insulin doses could be titrated/optimized based on an individual subject’s glucose levels. There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Accordingly, instant claims 1, 4, 5, 8-11, 13, and 20 are rendered obvious.
Regarding claim 2, the Baldwin and the clinical trial teach that the subject has type 2 diabetes (pp. 1, 9).
Regarding claims 6, 7, and 12, subjects included in the clinical trial were treated with basal insulin prior to participating in the trial (p. 9). The clinical trial does not expressly teach that the subjects included in the trial were treated with more than 10 or 20 U/day of basal insulin. However, such subjects were contemplated for inclusion in the clinical trial. The clinical trial specifically included type 2 diabetic subjects that were on basal insulin and assessed changes from baseline in fasting glucose and HbA1c levels. See also Strange.
Regarding claim 21, the clinical trial teaches that the method comprises improving glycemic control (pp. 8-9).
Accordingly, claims 1, 2, 4-13, 20, and 21 are rendered obvious in view of the teachings of the cited references.
Relevant Art Not Relied Upon
Lancaster et al (U.S. 2020/157169; earliest effective filing date 6/29/2018- cited in IDS filed 3/14/2024) teach insulin-Fc fusion proteins comprise an insulin polypeptide linked via a peptide linker. Lancaster et al teach subcutaneous injections were given no more frequently than once-weekly, and in some cases the injections were given at different intervals based on the pharmacodynamics of a given insulin-Fc fusion protein formulation. Subsequent injections for each insulin-Fc fusion protein were adjusted to higher or lower doses, depending on the demonstrated pharmacodynamics of the insulin-Fc fusion protein. For instance, if the dose of a first injection on day 0 was found to be ineffective at lowering blood glucose, the subsequent dose levels of injected insulin-Fc fusion protein were adjusted upward. In a similar manner, if the dose of a first injection on day 0 was found to lower glucose in too strong a manner, then subsequent dose levels of injected insulin-Fc fusion protein were adjusted downward. It was also found that interim doses or final doses could be adjusted in a similar manner as needed (para. [0181]).
Lancaster et al do not explicitly teach an insulin-fc fusion of insulin efitsora alpha.
Conclusion
No claims are allowed.
Claims 1-21 and 44-45 are pending. Claims 3, 14-19, and 44-46 are withdrawn.
Claims 1, 2, 4-13, 20, and 21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
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