DETAILED ACTION
Examiner acknowledges receipt of the reply filed 7/15/2026, in response to the restriction requirement mailed 1/16/2026.
Claims 1-11 are pending. Claims 4-6 have been withdrawn from further consideration for the reasons set forth herein.
Claims 1-3 and 7-11 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 11/30/2022 provides the following information:
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Election/Restrictions
Applicant’s election of Example 2 at Table 1, Patient 5, who is treated with the same first and second active ingredient is acknowledged. Election was made in the reply filed 7/15/2026. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-3 and 7-11 read on the elected species.
Claims 4-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 7/15/2026.
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.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “Disclosed herein …,”.
The use of the term Tween 20, Tween 40, Tween 88, Pluronic F68, 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.
See as-filed specification at para [0026].
Claim Objections
Claims 1, 2, 7, 8, 10, and 11 are objected to because of the following informalities:
Claim 1 should be amended to recite “subject in need thereof comprising” [at l. 3]; “or four times wherein the first” [at l. 14].
Claim 1 is further objected to because it contains redundant and superfluous language that fails to meaningfully limit the pending claim scope. Specifically, claim 1 recites
…with intervals between two sequential administrations of about 15 min or shorter, of about 30 min or shorter, of about 1 hour or shorter, of about 2 hours or shorter, of about 3 hours or shorter, or about 4 hours or shorter, of about 5 hours or shorter, or of about 6 hours or shorter…
However, the recitations of narrower ranges within a broader range recited within the same claim, are superfluous and non-limiting because all prior art that satisfies the broader range or narrower range will necessarily satisfy the broader range and therefore satisfy the claimed limitations. Redundant and superfluous language should be removed to enhance claim clarity and to minimize potential confusion. Examiner suggests the following amendments
…with intervals between two sequential administrations of about 15 min or shorter, to
The proposed amendments clarify the scope of claim 1 by removing superfluous and non-limiting language from the claim.
Claim 2 should be amended to recite “NASH; or wherein the subject has an elevated risk”.
Claim 7 is objected to because it contains redundant and superfluous language that fails to meaningfully limit the pending claim scope. Specifically, claim 7 recites
about 100 µg to about 1,000 µg, about 200 µg to about 900 µg, about 300 µg to about 800 µg, about 400 µg to about 700 µg, about 480 µg to about 600 µg.
However, the recitations of narrower ranges within a broader range recited within the same claim, are superfluous and non-limiting because all prior art that satisfies the broader range or narrower range will necessarily satisfy the broader range and therefore satisfy the claimed limitations. Redundant and superfluous language should be removed to enhance claim clarity and to minimize potential confusion. Examiner suggests the following amendments
about 100 µg to about 1,000 µg
The proposed amendments clarify the scope of claim 7 by removing superfluous and non-limiting language from the claim.
Claim 8 is objected to because it contains redundant and superfluous language that fails to meaningfully limit the pending claim scope. Specifically, claim 8 recites
…ratio of about 1, about 0.1 to about 10, about 0.5 to about 5, about 0.7 to about 2, about 0.8 to about 1.5, or about 0.9 to about 1.2.
However, the recitations of narrower ranges within a broader range recited within the same claim, are superfluous and non-limiting because all prior art that satisfies the broader range or narrower range will necessarily satisfy the broader range and therefore satisfy the claimed limitations. Redundant and superfluous language should be removed to enhance claim clarity and to minimize potential confusion. Examiner suggests the following amendments
…ratio of
The proposed amendments clarify the scope of claim 8 by removing superfluous and non-limiting language from the claim.
Claim 10 should be amended to recite: “wherein the second effective amount of the GLP-1 and/or GLP-1 analog(s) is
Claim 11 is objected to because it contains redundant and superfluous language that fails to meaningfully limit the pending claim scope. Specifically, claim 11 recites
…about 0.5 min to about 30 min, about 1 min to about 15 min, about 2 min to about 10 min, about 3 min to about 7 min, or about 5 min before or after meal.
However, the recitations of narrower ranges within a broader range recited within the same claim, are superfluous and non-limiting because all prior art that satisfies the broader range or narrower range will necessarily satisfy the broader range and therefore satisfy the claimed limitations. Redundant and superfluous language should be removed to enhance claim clarity and to minimize potential confusion. Examiner suggests the following amendments
…about 0.5 min to about 30 mina meal.
The proposed amendments clarify the scope of claim 11 by removing superfluous and non-limiting language from the claim.
Claim 11 should further be amended to recite “before or after a meal”.
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 1-3 and 7-11 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:
… administering to the subject a first effective amount of one or more first active ingredients selected from the group consisting of GLP-1 and GLP-1 analogs, wherein the first effective amount is administered continuously or administered intermittently with intervals between two sequential administrations of about 15 min or shorter, of about 30 min or shorter, of about 1 hour or shorter, of about 2 hours or shorter, of about 3 hours or shorter, or about 4 hours or shorter, of about 5 hours or shorter, or of about 6 hours or shorter; and
administering to the subject a second effective amount of one or more second active ingredients selected from the group consisting of GLP-1 and GLP-1 analogs once a day, twice a day, three times a day, or four time a day …
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: temporal relationship between the timing of administration of the first effective amount and the second effective amount. It is noted that the first effective amount is administered continuously or administered intermittently with intervals between two sequential administrations of 6 hours or less. Independently, the second effective amount is administered once a day, twice a day, three times a day, or four times a day. However, there is no timing relationship between the first effective dose and the second dose. It is unclear if the first effective amount and second effective amount are intended to be administered on the same day, separate months, or even years apart.
Claim clarification is required. Because claims 2, 3, and 7-11 depend from indefinite claim 1and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
Regarding claim 2 and the word “elevated” as used in “elevated risk”, the term “elevated” is a relative term which renders the claim indefinite. The term “elevated” is not defined by the claim, 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. It is unclear if “elevated” means “elevated to a statistically and practically significant extent”, 1% over basal level, 10% over basal level, 7-fold more than average, etc., etc. Accordingly, claim 2 is rejected as indefinite.
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 1-3 and 7-11 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 courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
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. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In the instant case, claim 1 is directed to a dosing regimen for the treatment of diabetes, obesity, overweight, non-alcoholic fatty liver disease (NAFLD), and/or non-alcoholic steatohepatitis (NASH) in a subject comprising: administering to the subject a first effective amount of one or more first active ingredients selected from the group consisting of GLP-1 and GLP-1 analogs, wherein the first effective amount is administered continuously or administered intermittently with intervals between two sequential administrations of about 15 min or shorter, of about 30 min or shorter, of about 1 hour or shorter, of about 2 hours or shorter, of about 3 hours or shorter, or about 4 hours or shorter, of about 5 hours or shorter, or of about 6 hours or shorter; and administering to the subject a second effective amount of one or more second active ingredients selected from the group consisting of GLP-1 and GLP-1 analogs once a day, twice a day, three times a day, or four time a day to treat or prevent diabetes, obesity, overweight, NAFLD, and/or NASH in the subject, and the first and the second active ingredients are the same or different. Claim 3 recites wherein the GLP-1 analogs are selected from the group consisting of GLP-1 (7-37), GLP-1 (7-36), and GLP-1 (7-35). Claim 9 recites wherein the first effective amount of the GLP-1 and/or GLP-1 analog(s) is administered at a constant or a variable dosing rate. Claim 10 recites wherein the second effective amount of the GLP-1 and/or GLP-1 analog(s) is administered at the same or different dosages at each administration.
The specification states at para [0014]: The terms "treat," "treating," and "treatment" as used herein with regard to a condition refers to alleviating the condition partially or entirely, preventing the condition, decreasing the likelihood of occurrence or recurrence of the condition, slowing the progression or development of the condition, or eliminating, reducing, or slowing the development of one or more symptoms associated with the condition.
The specification does not expressly define GLP-1 analogs. The specification indicates that GLP-1 analogs include GLP-1 (7-37), GLP-1 (7-36), and GLP-1 (7-35). A recombinant human GLP-1 (7-36) of SEQ ID NO:1 is also known as beinaglutide. SEQ ID NO:2 correlates with GLP-1 (7-35), and SEQ ID NO:3 correlates with SEQ ID NO:3.
Example 1 discloses subcutaneous administration of Beinaglutide and oral administration of metformin in type 2 diabetic patients. Example 2 discloses continuous subcutaneous administration of beinaglutide, in combination with one-time subcutaneous administration of beinaglutide before each of three meals/day. The patients optional received insulin glargine or metformin. See specification at pp. 14-18.
Thus, the only GLP-1/GLP1 analog reduced to practice was beinaglutide.
The specification does not provide ample written description for a dosing regimen comprising GLP-1/GLP-1 analogs since the claims do not describe a single structural feature. The specification does not clearly define or provide examples of what qualify as GLP-1/GLP-1 analogs of the claimed invention.
As stated earlier, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. As noted above, the terms GLP1 and “GLP1 analogs” are not expressly defined.
The possible structural variations are limitless to any class of peptide that can form peptide bonds, and make up the class of GLP1 analogs. It must not be forgotten that the MPEP states that if a peptide is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. Here, though the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond compounds disclosed in the examples in the specification. Moreover, the specification lack sufficient variety of species to reflect this variance in the genus since the specification does not provide any examples of what amino acids are required to have the function of GLP1 analogs. There is no guidance as to criticality of amino acid content/sequence or length.
Peptides that are construed as “GLP1 analogs” may not have functionality. Yampolsky et al (Genetics, 2005, 170: 1459-1472) teach the effect of an amino acid exchange/mutation on a peptide (see for example, Table 3). Thus, the identity of amino acids are not only in amino acid sequence order but also in conformational/structural order can be critical to the overall function of the peptide.
Per the specification at para [0015], beinaglutide is a GLP1(7-36) analog and “is essentially the same as the active form of circulating GLP-1 except for the endogenous amidation where NH2 in the natural form is replaced by OH group in the recombinant peptide”. As evidenced by Zhang et al (Obes Sci Pract 2019, 10 p- cited in IDS filed 1/5/2024), beinaglutide has a short half-life (15 min) and duration of action (2 h) (p. 373).
Abliglutide is another GLP-1 agonist. As evidenced by Tanzeum FDA label (FDA, 1/1/2014, 56 pp - cited in IDS filed 5/01/2025), Tanzeum (albiglutide) is a once weekly subcutaneous injection for patients with type 2 diabetes (pp. 1-2). Abliglutide, differs from human GLP-1 fragment sequence 7 – 36, modified with a glycine substituted for the naturally-occurring alanine at position 8 in order to confer resistance to dipeptidylpeptidase IV (DPP-IV) mediated proteolysis. The human albumin moiety of the recombinant fusion protein, together with the DPP-IV resistance, extends the half-life allowing once-weekly dosing (ll. 420-430). Albiglutide has a half-life of 5 days. Id.
Beinaglutide and albiglutide, both GLP1 (7-36) analogs, may be structurally similar but greatly differ from each other in terms of pharmacokinetic parameters, as indicated by their different half-lives and dosing times.
Smith et al (J Med Chem 61:4273-4282 (2018)) teach that drug half-life has important implications for dosing regimen and peak-to-trough ratio at the steady state (abstract). From a drug discovery perspective, t1/2 is defined as the time required for the concentration of a drug (typically in blood or plasma) to reduce to half of its initial
value when the concentrations of the drug are in simple exponential (log−linear) decline. Despite its relatively simple visualization and mathematical derivation, the role of t1/2 in
drug discovery and development is surprisingly complex. The importance of drug distribution in defining t1/2 is likely to be the major determinant of dosing frequency for many drugs (p. 4273). Drugs can further exhibit quite different t1/2 in different patients and populations leading to the need for different dosing regimens (p. 4280).
Thus, not only is the amino acid sequence relevant to compounds that can be categorized as GLP1/GLP1 analogs, the half-life of a given GLP1/analog is critical to whether or not that peptide can be used in the instantly claimed dosing regimen for the treatment of diabetes, obesity, overweight, NAFLD, and/or NASH.
Not all GLP1 analogs of the prior art that satisfy the function of “GLP1 analog” would appear to have utility/compatibility in the claimed dosing regimen. For instance, Petri et al (Diabetes Ther 9:1533-1547 (2018)) teach that semaglutide GLP1(7-37) analog is administered subcutaneously once a week (e.g., abstract, pp. 1534, 1536). This GLP1 analog would unlikely be suitable for use in the instant dosing regimen- wherein the effective amount is administered continually or twice within 6 hours [first effective amount] or up to four times a day [second effective amount] when it is FDA approved for once-weekly treatment.
Examiner reiterates- the specification is limited to teaching a dosing regimen of 1 GLP1 agonist, beinaglutide. This is not a sufficient amount of examples provided to encompass the numerous characteristics of the whole genus claimed. The skilled artisan cannot extrapolate to other GLP1s and analogs that can be used in the instant dosing regimens claims, based on the single embodiment of beinaglutide.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claims 1-3 and 7-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating [alleviating] diabetes, obesity, overweight, non-alcoholic fatty liver disease (NAFLD), and/or non-alcoholic steatohepatitis (NASH) with beinaglutide, does not reasonably provide prevention of any disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Liebel-Flarsheim Co. v. Medrad, Inc. 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
(1) Breadth of claims. Claim 1 is directed to a dosing regimen for the treatment of diabetes, obesity, overweight, non-alcoholic fatty liver disease (NAFLD), and/or non-alcoholic steatohepatitis (NASH) in a subject comprising: administering to the subject a first effective amount of one or more first active ingredients selected from the group consisting of GLP-1 and GLP-1 analogs, wherein the first effective amount is administered continuously or administered intermittently with intervals between two sequential administrations of about 15 min or shorter, of about 30 min or shorter, of about 1 hour or shorter, of about 2 hours or shorter, of about 3 hours or shorter, or about 4 hours or shorter, of about 5 hours or shorter, or of about 6 hours or shorter; and administering to the subject a second effective amount of one or more second active ingredients selected from the group consisting of GLP-1 and GLP-1 analogs once a day, twice a day, three times a day, or four time a day to treat or prevent diabetes, obesity, overweight, NAFLD, and/or NASH in the subject, and the first and the second active ingredients are the same or different. Claim 3 recites wherein the GLP-1 analogs are selected from the group consisting of GLP-1 (7-37), GLP-1 (7-36), and GLP-1 (7-35). Claim 9 recites wherein the first effective amount of the GLP-1 and/or GLP-1 analog(s) is administered at a constant or a variable dosing rate. Claim 10 recites wherein the second effective amount of the GLP-1 and/or GLP-1 analog(s) is administered at the same or different dosages at each administration.
The specification states at para [0014]: The terms "treat," "treating," and "treatment" as used herein with regard to a condition refers to alleviating the condition partially or entirely, preventing the condition, decreasing the likelihood of occurrence or recurrence of the condition, slowing the progression or development of the condition, or eliminating, reducing, or slowing the development of one or more symptoms associated with the condition.
The specification does not expressly define GLP-1 analogs. The specification indicates that GLP-1 analogs include GLP-1 (7-37), GLP-1 (7-36), and GLP-1 (7-35). A recombinant human GLP-1 (7-36) of SEQ ID NO:1 is also known as beinaglutide. SEQ ID NO:2 correlates with GLP-1 (7-35), and SEQ ID NO:3 correlates with SEQ ID NO:3.
(2) The nature of the invention and predictability in the art: The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
(3) Direction or Guidance and working examples: That provided is very limited. Example 1 discloses subcutaneous administration of Beinaglutide and oral administration of metformin in type 2 diabetic patients. Example 2 discloses continuous subcutaneous administration of beinaglutide, in combination with one-time subcutaneous administration of beinaglutide before each of three meals/day. The patients optional received insulin glargine or metformin. See specification at pp. 14-18.
The only GLP1 administered to subjects was beinaglutide.
There are no examples of prevention of any disease/disorder.
(4) State of the Prior Art: the following provides some of the diseases encompassed by the instant claims, but is not deemed to be a comprehensive listing.
Pociot et al (Lancet 387: 2331-39 (2016)) teach that 1 diabetes is diagnosed at the end of a prodrome of β-cell autoimmunity. The disease is most likely triggered at an early age by autoantibodies primarily directed against insulin or glutamic acid decarboxylase, or both, but rarely against islet antigen-2. After the initial appearance of one of these autoantibody biomarkers, a second, third, or fourth autoantibody against either islet antigen-2 or the ZnT8 transporter might also appear. The larger the number of β-cell autoantibody types, the greater the risk of rapid progression to clinical onset of diabetes (abstract). Children born in families with type 1 diabetes have different lifetime risks depending on whether the mother (3%), father (5%), or a sibling (8%) has the disease. Type 1 diabetes is known to be strongly associated with HLA-DR3-DQ2 and HLA-DR4-DQ8 haplotypes, alone or in combination (p. 2331). 58 genomic regions show substantial genome-wide evidence for type 1 diabetes association and about 50 genes are suggested to be potential causal disease genes (p. 2334; table pp 2335-2336).
As taught by the CDC, type 1 diabetes can be treated but not prevented (Type 1 diabetes, CDC, accessed 9/17/2025 at URL cdc.gov/diabetes/about/about-type-1-diabetes.html, pp. 1-3).
: Schaffler et al. (Nat. Rev. Gastroenterol. Hepat. 2:273-280 (2005)), is a review article discussing the role of visceral adipose tissue in fatty liver and nonalcoholic steatohepatitis (abstract). Nonalcoholic fatty liver disease comprises hepatic steatosis (fatty liver disease), nonalcoholic steatohepatitis (NASH), fibrosis and liver cirrhosis (p. 273, para. 1). There is a positive correlation between hepatic insulin resistance and liver fat content, and most obese patients have evidence of fatty liver or even NASH, a condition in which fat deposition in the liver is accompanied by fibrosis and necroinflammation (Figure 1). The high extent of lipid deposition and lipolysis in visceral adipose tissue (VAT) leads to an increased flux of free fatty acids (FFAs) to the liver via the portal vein. Id. at para. 2. FFAs are stored as triglycerides in the cytoplasm and are used for the assembly of the main precursor of LDL, VLDL, in the endo plasmatic reticulum. Id. at para. 2. The chronic hepatic lipid overload results in lipid storage and insulin resistance. Id. High levels of glucose activate the transcription factor carbohydrate responsive element binding protein, inducing the synthesis of FFAs by the liver leading to development of fatty liver (Figure 2). There is growing evidence that obesity and especially excessive visceral fat disturb the secretion of adipocytokines - secretory products derived from adipose tissue- thus contributing to the pathologic features of NASH (Table 1).
Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic steatosis (retention of lipids in liver cells) ((Chalasani et al., Hepatology 55:2005-2023 (2012))- p. 2005). In the majority of patients, NAFLD is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. NAFLD is histologically further categorized into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) (Table 3). Treatment of NAFLD involves lifestyle changes (diet and exercise), insulin sensitizing agents, bariatric surgery, statins, vitamin E, and thiazolidinediones (pp. 2011-2014).
Nonalcoholic steatohepatitis (NASH) (Merck Manual, accessed 7/29/2016 at URL merckmanual.com, pp. 1-3) teaches that the pathophysiology of Nonalcoholic steatohepatitis (NASH) involves fat accumulation (steatosis), inflammation, and, variably, fibrosis. Steatosis results from hepatic triglyceride accumulation. Risk factors such as obesity, type 2 diabetes mellitus, or dyslipidemia and in patients with unexplained laboratory abnormalities suggesting liver disease. The most common laboratory abnormalities are elevations in aminotransferase levels. Prognosis is hard to predict. Most patients do not develop hepatic insufficiency or cirrhosis. However, some drugs (e.g., cytotoxic drugs) and metabolic disorders are associated with acceleration of NASH. Prognosis is often good unless complications develop. Treatment involves elimination of causes and control of risk factors. The only widely accepted treatment goal is to eliminate potential causes and risk factors, e.g., discontinuation of drugs or toxins, weight loss, and treatment for dyslipidemia or treatment for hyperglycemia. Several drugs, e.g., metformin and betaine have not been proved effective.
Smith et al (J Med Chem 61:4273-4282 (2018)) teach that drug half-life has important implications for dosing regimen and peak-to-trough ratio at the steady state (abstract). From a drug discovery perspective, t1/2 is defined as the time required for the concentration of a drug (typically in blood or plasma) to reduce to half of its initial
value when the concentrations of the drug are in simple exponential (log−linear) decline. Despite its relatively simple visualization and mathematical derivation, the role of t1/2 in
drug discovery and development is surprisingly complex. The importance of drug distribution in defining t1/2 is likely to be the major determinant of dosing frequency for many drugs (p. 4273). Drugs can further exhibit quite different t1/2 in different patients and populations leading to the need for different dosing regimens (p. 4280).
(6) Skill of those in the art:
The relative skill of those in the art: MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” /d. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
(7) The quantity of experimentation needed: Owing especially to factors 1-6 the quantity is expected to be high.
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3 and 7-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Alessi et al (U.S 2011/0076317).
Alessi teach treatment methods for a disease or condition (e.g., obesity, diabetes, NASH, NFALD , in a subject in need of such treatment, by injection, with improved treatment outcomes, 100% treatment compliance, and reduced side effects. The method includes providing continuous delivery of a drug (e.g., exenatide) from an implanted osmotic delivery device, wherein substantial steady-state delivery of the drug at therapeutic concentrations is achieved (abstract; paras [0012], [0178]-[0180], [0189]). Alessi teach administration of a first continuous administration of exenatide (GLP1 analog), followed by a second continuous administration [construed as reading on second effective amount] of exenatide in patients with type 2 diabetes. The second effective amount is greater than the first effective amount (e.g., Example 3, claims 1, 15). Accordingly, the limitations of claims 1, 9, and 10 are satisfied.
Regarding claim 2, Alessi teach that the subject has diabetes (e.g. abstract, paras [0012], [0078], ]0178]-[0179], Exs 1-4). Regarding claim 3, other GLP1 agonists include lixisenatide, GLP-1(7-36), liraglutide, albiglutide, and taspoglutide (e.g., paras [0084], [0093], [0122]-[01224], claim 23]). Regarding claim 7, Allessi teaches continuous delivery of 80 µg/day [reads on about 100 µg] (e.g., paras [0018], [0020], [0085]-[0088], [0183]-[0185], Exs 2-4). Regarding claim 8, Example 3 teaches total daily amounts of a first effective amount of 20 µg /day was increased at week 13 to a second effective amount of 60 µg/day [reads on ratio of 1:3 or 0.33] (e.g., para [0229]). It is further noted that a group was increased to 80 µg /day. Given the broadest reasonable claim interpretation, the first and second effective amounts can be administered at different intervals, including separate weeks. Regarding claim 11, Alessi teaches a second continuous administration. Thus, the second effective amount is construed as administered within the recited time frame before or after a meal.
Conclusion
No claims are allowed.
Claims 1-11 are pending. Claims 4-6 have been withdrawn.
Claims 1-3 and 7-11 are rejected.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
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