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 .
Status of the Claims
Amendment filed on June 12, 2023 is acknowledged.
Claims 1-7, 10-18 and 25 are amended.
Claims 29-51 are canceled.
Claims 21-23, 26 and 27 are withdrawn.
Claims 1-20, 24, 25 and 28 are pending and under consideration.
Information Disclosure Statement (IDS)
The information disclosure statement (IDS) filed on 03/01/2024 and 03/14/2024 are considered, initialed and are attached hereto.
Priority
Applicant’s claim for benefit of and priority to U.S. provisional patent application 63/125,165, filed 12/14/2020, is acknowledged.
The subject matter of claims 1-20, 24-25 and 28, where the insulin efsitora alfa is administered on fixed doses selected from the group consisting of 100, 150, 250 U and 400 U, and where the aqueous composition comprising phosphate, glycerol and poloxamer at claimed concentration and the pH at the claimed value, is not included in the provisional application 63/125,165, and therefore the priority is not granted. In the provisional application, the listed fixed doses are 1.5, 3.0, 4.5 and 6.0 mg, while the cited doses in the claims corresponds to 2.85, 4.3, 7.15 and 11.45 mg (instant specification page 8 line 2-3). While the loading dose of 250 U is listed in the provisional application specification (see table 4 and table 19), it is listed with 16 dose options and not listed as an option for fixed dose regimen. The priority of claims 1-20, 24-25 and 28 are December 14, 2021 as PCT/US21/63235.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-20, 24, 25 and 28 in the reply filed on 03/09/2026 is acknowledged.
Claims 21-23, 26 and 27 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups II and Group III, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/09/2026.
The requirement is deemed proper and is therefore made FINAL.
Applicant’s comments regarding filing one or more divisional or continuation applications to claim any non-elected subject matter are noted.
Applicant is respectfully reminded that where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
Claim Objections
Claims objections are as follows:
Claims 1 and 18 are objected to because of the following informalities: insulin efistora alfa in claim 1 should be spelled as insulin efsitora alfa; “wherein insulin efsitora alfa is in administered in an aqueous composition” in claim 18 has an extra word ‘in’ (underlined). Appropriate correction is required.
As per the above, the status of claims 26-28 are not clearly marked with claim identifiers. Applicants’ attention is directed to the proper method of amending the claims as per MPEP 714, 37 CFR 1.121 Manner of making amendments in application. Applicants’ attention is directed to the claims 7-15 which applicants list as “(Withdrawn)” but show no text for the claims.
37 CFR 1.121 Manner of making amendments in applications
(3) When claim text in clean version is required. The text of all pending claims not being currently amended shall be presented in the claim listing in clean
version, i.e., without any markings in the presentation of text. The presentation of
a clean version of any claim having the status of "original," "withdrawn" or
"previously presented" will constitute an assertion that it has not been changed
relative to the immediate prior version, except to omit markings that may have
been present in the immediate prior version of the claims of the status of
"withdrawn" or "previously presented." Any claim added by amendment must be
indicated with the status of "new" and presented in clean version, i.e., without
any underlining.
Please use proper markings in all future amendments. This is required to clarify the record and prosecution and avoid issues that result from a lack of clarity of the record and prosecution.
Specification Objections
Specification objection as follows:
The use of the term TWEEN®, KWIKPEN®, BASAGLAR®, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Embodiments 1-65 on pages 11-19 are labeled as embodiments but written using claim language. Please clarify if these embodiments are intended as embodiment or claims. Please note that claims should be held separate from the specification.
Claim Rejections - 35 USC § 112
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.
Claims 6 and 24 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 6 is dependent on claim 5, which is dependent on claim 4. Claim 4 is drawn to the method of claim 1 wherein the patient's dose is increased if the patient's fasting glucose (FG) is > 130 mg/dL after treatment with a first fixed dose for at least 4 weeks. Claim 5 is drawn to the method of claim 4 wherein the patient's dose is only increased if the patient had 0 episodes of blood glucose < 70 mg/dL. Claim 6 is drawn to the method of claim 5 wherein the patient's dose is decreased if the patient's FG is < 80 mg/dL. Claim 4 limits the patient’s fasting glucose (FG) to >130 mg/dL, where claim 6 is drawn to patient’s FG to < 80 mg/dL. The range of <80 mg/dL in claim 6 is not included in the range >130 mg/dL in claim 4 and thus fails to include all the limitations of claim 4 and also fails to further limit the subject matter of claim 4.
Claim 24 is dependent on claim 23, which is withdrawn.
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.
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 3-6 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 claims are drawn to increasing or decreasing the dose of the insulin efsitora alfa based on the patient’s fasting glucose, blood glucose and/or if the patient needs additional glycemic control. However, the claims fail to particularly point out how much dose should be increased or decreased. For example, it is unclear if the dose is increased to the next higher dose (such as from 150 U to 250 U), or could be increased from 100U to 400 U based on how high patient’s fasting glucose is above 130 mg/dL. It is also unclear what the dose would be if the patient has reached the highest dose (400 U) but the patient still need additional glycemic control (such as fasting glucose is still above 130 mg/dL).
Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-20, 24, 25 and 28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicant are claiming and what Applicant have possession of.
The claims are drawn to a method of providing glycemic control in patient in need thereof with type 2 diabetes comprising administering to said patient once-weekly a fixed dose of insulin efsitora alfa selected from the group consisting of 100, 150, 250 and 400U, and increasing or decreasing the doses based on patients’ response.
The specification lists two clinical studies using fixed doses of insulin efsitora alfa: one study at 100 U, 150 U, 250 U and 400U in a phase 3 trial (page 19 lines 18-26), and a second study using another exemplary regimen including 4 fixes doses in mg (e.g., 1.5, 3.0, 4.5 and 6.0 mg) (page 24 lines 8-9). The corresponding doses of insulin efsitora alfa at 100, 150, 250 and 400U are interpreted as 2.85, 4.3, 7.15 and 11.45 mg, respectively, based on the description on page 7 line 31 – page 8 line 5 of the instant specification. The specification states the fixed dosing regimen is developed by modeling and simulation approaches utilizing Phase 1 and 2 clinical data (page 19 lines 15-18), but fails to describe how these four doses (100, 150, 250 and 400U) are chosen and their effect in providing or improving glycemic control for a patient in need of using the claimed method.
The specification fails to describe how the fixed doses are chosen. In the state of the art, Ohwaki et al (Diabetes 2021; 70(supplement_1):743-P) and its corresponding clinical trial study design on clinicaltrials.gov (identifier: NCT03603704, V16, 2020-11-13) teach that BIF (insulin efsitora alfa) at doses 1 and 2 (5 mg and 10 mg respectively) significantly decreased fasting glucose levels in Japanese patients with type 2 diabetes. Rosenstock et al (N Engl J Med 2025: 393:325-35) teaches in a phase 3 clinical trial treating participants with type 2 diabetes with the weekly fixed-dose insulin efsitora (100, 150, 250 and 400U), targeting fasting blood glucose levels of 80 to 130 mg per deciliter, the fixed doses were determined on the basis of simulation outputs, input from experts on treat-to-target strategies and data analytics on real-world insulin doses used (abstract, page 327 right column first paragraph), but no further details are provided. Therefore, neither the specification nor the state of the art teaches how the four fixed doses are chosen.
In addition, the specification fail to teach if the claimed method work in providing or improving glycemic control in a patient with type 2 diabetes. In the state of the art, Rosenstock et al (N Engl J Med 2025: 393:325-35) teaches in the phase 3 clinical trial treating participants with type 2 diabetes with the weekly fixed-dose insulin efsitora (100, 150, 250 and 400U), 24% of the participants transitioned to treatment with efsitora in variable doses higher than 400 U when their fasting blood glucose level did not reach the target of 80 – 130 mg/dL after 4-weeks of treatment with a fixed dose of 400 U (page 331-332 section Efficacy End Points, page 334 left column last paragraph). Therefore, the state of the art teaches the claimed method in the instant application might not work in some patients with type 2 diabetes.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, ‘does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the “written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Relevant art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Rosenstock et al (N Engl J Med 2020;383:2107-16, published on September 22, 2020) teaches the starting dose of Insulin icodec, which is designed for once-weekly administration to treat type 2 diabetes, is 70 U once per week and mean weekly dose is about 229 U per week.
Baldwin et al (US 20160324932 A1, published November 10 2016, filed in IDS submitted on 03/01/2024) teaches a method of treating a patient with diabetes mellitus, comprising administering therapeutically effective amount insulin efsitora alfa, at ranges from 0.01 nmol/kg to about 100 nmol/kg.
Lancaster et al (US 2020/0157169 A1, published May 21 2020, filed in IDS submitted on 03/14/2024) teaches an insulin-Fc fusion protein for treating diabetes in animals wherein the insulin-Fc is administered once weekly at a dose of 0.4-4.0 U/kg to dogs.
Ohwaki et al (Diabetes 1 June 2021; 70 (Supplement_1): 742–P) teaches administering BIF (LY3209590) to patients with T2DM at three different fixed doses and BIF significantly decreases fasting glucose levels for the patients at all three doses tested.
Anonymous (A Study of LY3209590 in Japanese Participants with Type 2 diabetes, ClinicalTrials.gov ID NCT03603704, date of records 2020-11-13), which provides more details on the study protocol which Ohwaki reported results for, teaches insulin efsitora alfa (LY3209590) is administered to patients at dose 5, 10 and 20 mg. In addition, one of the inclusion criteria for the trial is patient having hemoglobin A1c (HbA1c) ≥7.0% and ≤10.0% (between 7 and 10%).
Anonymous (I8H-MC-BDCM Clinical Protocol, clinicaltrials.gov identifier NCT03736785, date Aug-31-2018) teaches that due to the long half-life of LY3209590 (insulin efsitora alfa), the change in fasting glucose response following dose adjustment may take several weeks to reach new level; therefore less frequent dose adjustment is recommended to minimize prolonged variation in glycemic control (Appendix 7). I8H also teaches the time to reach steady-state glucose level is estimated between 4-10 weeks based on the long half-life of LY3209590 (section 5.5). In addition, the protocol also teaches the doses of LY3209590 are based on participants’ fasting glucose and hypoglycemic events, and the doses can be adjusted based on therapeutic effects and safety (whole doc).
Howard-Thompson et al (Am Fam Physician. 2018;97(1):29-37) teaches the American Diabetes Association suggests the use of long-acting (basal) insulin to augment therapy with one or two oral agents or one oral agent plus a glucagon-like peptide 1 receptor agonist when the A1C level is 9% or more, especially if the patient has symptoms of hyperglycemia in patients with type 2 diabetes. It also teaches that for healthy patient, reasonable A1C (HbA1c) goals should be <7.5%, or 90-130 mg/dL for fasting glucose level. In addition, based on the fasting blood glucose levels, the insulin doses should be adjusted.
Conclusion
No claims are allowed.
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/TIAN YANG/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
Prosecution Insights