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 .
Election/Restrictions
Applicant’s election of species for Formula 1: (I) X1 = Y, X2=Aib, X7=T, X10= Y, ….., X29 = T, and X30 =C; (II) amino acid sequence SEQ ID NO: 37; and (III) an exendin-4 derivative in the reply filed on 5/15/2026 is acknowledged. 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)).
Status of Application, Amendments, And/Or Claims
Claims 1-8, 10, 13-17 and 20-25 are pending and under examination to the extent they read on elected species.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 10/05/2023, 3/28/2025 and 4/13/2026 have been considered. The crossed-out reference # 15 of the IDS dated 10/5/2023 (international search report for PCT/KR2022/005188 of 7/15/2022) is not provided.
Claim Rejections - 35 USC § 112
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 1-8, 10, 13-17 and 20-25 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 written description in this case only sets forth a method of treating chronic renal disease comprising administering to a subject in need thereof a pharmaceutical composition comprising a glucagon derivative of amino acid sequence of SEQ ID NO: 37, and therefore the written description is not commensurate in scope with “a method of treating chronic renal disease comprising administering to a subject in need thereof a pharmaceutical composition comprising any glucagon derivative of Formula I, SEQ ID NO: 46”.
The claims broadly encompass many thousands if not millions of glucagon derivative of General Formula I, SEQ ID NO: 46 for the treatment of chronic renal disease in a subject in need thereof. The specification on pg.62, Example 3, discloses that the administration of glucagon derivative of SEQ ID NO: 37 at 3.9 nmol/kg Q3D, subcutaneously resulted in a significant difference as compared to control group (Fig. 1). To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. Some of the factual considerations that are weighed when determining a written description include the level of skill and knowledge in the art, the disclosure of complete or partial structures, the disclosure of physical and or chemical properties, adequate disclosure of the functional characteristics, the correlation between structure and function, and disclosure of methods of making.
WO 2018/004283 (IDS) teaches making glucagon derivatives and conjugate thereof for therapeutic uses in metabolic syndrome, hypoglycemia and concomitant hyperinsulinemia (abstract). Lee et al. (WO 2017/003191) teach a number of long-acting glucagon derivative and conjugate thereof (abstract). They teach a formula I, SEQ ID NO: 46 similar to one being instantly claimed and a method of reducing body weight in a subject. However, the instant claims are drawn to treating chronic renal disease.
In the instant case, the specification at pg. 57+, Example 1 only adequately discloses that 90% of peptide have poor receptor binding activity and about 4 peptides including the peptide of SEQ ID NO: 37 with a better in vitro activity relative to SEQ ID NO: 1. The specification does not describe any sufficient number of species (only the glucagon derivative of SEQ ID NO: 37) of the claimed genus that improves or treats chronic renal condition. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, states 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, for purposes of the written description inquiry, is 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).
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states an adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.
As discussed above, the skilled artisan cannot envision the detailed genus of “any glucagon derivative of Formula I for treating chronic renal diseases” and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of making a mutation. The compound itself is required. See Fiers v.Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen v.Baird, 30 Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 148 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class.
Therefore, only a method of treating chronic renal disease comprising administering to a subject in need thereof a pharmaceutical composition comprising the polypeptide of amino acid sequence of SEQ ID NO: 37, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 112-scope of enablement
Claims 1-8, 10, 13-17 and 20-25 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 a method of treating chronic renal disease in a subject in need thereof comprising administering a composition comprising a polypeptide having amino acid sequence of SEQ ID NO: 37, does not reasonably provide enablement for a method of treating chronic renal disease in a subject in need thereof comprising administering any glucagon derivative comprising amino acid sequence of Formula I, SEQ ID NO: 46. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
In In re Wands, 8USPQ2d, 1400 (CAFC 1988) page 1404, the factors to be considered in determining whether a disclosure would require undue experimentation include: (1) Nature of the invention, (2) the state of the prior art, (3) the predictability or lack thereof in the art, (4) the amount of direction or guidance present, (5) the presence or absence of working examples, (6) the breath of the claims, (7) the quantity of experimentation needed, (8) relative skill of those in the art.
The instant disclosure fails to meet the enablement requirement for the following reasons:
Claims 1-8, 10, 13-17 and 20-25 are broadly drawn to a method of treating chronic renal disease comprising administering to a subject in need thereof a pharmaceutical composition comprising any glucagon derivative of Formula I, SEQ ID NO: 46.
The state of the prior art and the predictability or lack thereof in the art:
WO 2018/004283 (IDS) teaches making glucagon derivatives and conjugate thereof for therapeutic uses in metabolic syndrome, hypoglycemia and concomitant hyperinsulinemia (abstract). Lee et al. (WO 2017/003191) teach a number of long-acting glucagon derivative and conjugate thereof (abstract). They teach a formula I, SEQ ID NO: 46 similar to one being instantly claimed and a method of reducing body weight in a subject. However, the instant claims are drawn to treating chronic renal disease. Patel et al teach that co-agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptors ameliorates kidney injury in murine models of obesity and diabetes mellitus (see the title, abstract, pg. 83 Results). However, the art does not teach that administering glucagon derivative can treat chronic renal disease in a subject in need thereof. Therefore, it is unpredictable and would require a large amount of experimentation to treat chronic renal disease in a patient need thereof.
The amount of direction and guidance present and the presence or absence of working examples: Given the teachings found in the art, detailed teachings are required to be present in the disclosure in order to enable the skilled artisan to practice the invention as claimed. These teachings are absent. The specification at pg.62, Example 3, discloses that the administration of glucagon derivative of SEQ ID NO: 37 at 3.9 nmol/kg Q3D, subcutaneously in a spontaneous hypertensive rat model resulted in a significant difference as compared to control group (Fig. 1). However, the specification at pg. 57+, Example 1 only adequately discloses that 90% of peptide have poor receptor binding activity and about 4 peptides including the peptide of SEQ ID NO: 37 with a better in vitro activity relative to SEQ ID NO: 1. The art or the specification is devoid of sufficient examples of glucagon derivatives that support a method of treating chronic renal disease in a subject in need thereof. Therefore, it is unpredictable how one of the skill in the art can practice the instantly claimed invention.
The breadth of the claims and the quantity of experimentation needed: Due to the large quantity of experimentation necessary to chronic renal disease comprising administering any glucagon derivative of amino acid sequence of Formula I, ( SEQ ID NO: 46) to a subject in need thereof, the lack of direction/guidance presented in the specification regarding the same, the state of the prior art which establishes the unpredictability about chronic renal disease in a subject, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
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.
Claim(s) 1-8, 10, 13-17 and 20-25 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (IDS, WO 2017/003191) in view of Patel et al. (IDS, World J. Diabetes, 2018, 9: 80-91) or Parker et al. (US Pub. No. 2021021310, claims priority to US Provisional 62959698 filed on 1/10/2020).
The instant claims are broadly drawn to a method for treating chronic renal disease comprising administering to a subject in need thereof a pharmaceutical composition comprising a glucagon derivative and a pharmaceutically acceptable excipient wherein the glucagon derivative is from a general formula 1, amino acid sequence of SEQ ID NO: 46 ( X 1-X2-QGTF-X7-SD-X10-S-X 12-X 13-X 14-X 15-X 16-X 17-X 18-X 19-X20-X21-F-X23- X24-W-L-X27-X28-X29-X30 and the positions X1, X2, … are defined in claim 1, with the proviso that when the amino acid sequence of General Formula 1 is identical to SEQ ID NO: 1, or SEQ ID NO: 2, it is excluded. The method of claim 1, wherein the peptide is in the form of a long-acting conjugate, which is represented by the following Formula 1: [Formula 1] X-L-F wherein X represents a peptide including the amino acid sequence of General Formula 1; L represents a linker containing ethylene glycol repeating units; F represents an immunoglobulin Fc region; and - represents covalent linkages between X and L and between L and F, respectively, wherein the peptide includes an amino acid sequence selected from the group consisting of SEQ ID NOS: 7 to 11, and 13 to 25, 27, 29, 31, 33, and 35 to 45 (claims 4-5). The method of claim 1, wherein the composition exhibits one or more of the following characteristics of: (a) lowering the blood pressure; (b) reducing albumin excretion; (c) reducing proteinuria; and (d) restoring the renal function (claims 6-7). The method of claim 1, wherein the C- terminus of the peptide is amidated; or wherein the peptide has a ring formed between amino acid residues (claim 8). The method of claim 2, wherein the immunoglobulin Fc region is aglycosylated; wherein the immunoglobulin Fc region is an IgG4 Fc region; or- wherein the immunoglobulin Fc region is a dimer consisting of two polypeptide chains, and one end of L is linked to only one polypeptide chain of the two polypeptide chains, wherein, in the long-acting conjugate, L is linked to F and X by covalent linkages formed by reacting one end of L with an amine group or a thiol group of F and by reacting the other end of L with an amine group or a thiol group of X, respectively, wherein the formula weight of a moiety of the ethylene glycol repeating units in L is in the range of 1 kDa to 100 kDa (claims 10, 13-15), wherein the composition further comprising a GLP-1 receptor agonist (glucagon-like peptide 1 receptor agonist). The method of claim 16, wherein the GLP- 1 receptor agonist is in the form of a long-acting conjugate, in which the GLP-1 receptor agonist is linked to the immunoglobulin Fc region, wherein the GLP- 1 receptor agonist is an imidazo-acetyl exendin-4 (CA exendin-4) linked to the immunoglobulin Fc region via a linker containing ethylene glycol repeating units. The method of claim 2, wherein the composition further comprises a GLP-1 receptor agonist (glucagon-like peptide 1 receptor agonist). The method of claim 1, further comprising administering to the subject a GLP-1 receptor agonist simultaneously, individually, sequentially, or in reverse order (claim 23), wherein the GLP-1 receptor agonist is in the form of a long-acting conjugate, in which the GLP-1 receptor agonist is linked to the immunoglobulin Fc region (claim 24), wherein the GLP-1 receptor agonist is an imidazo-acetyl exendin-4 (CA exendin-4) linked to the immunoglobulin Fc region via a linker containing ethylene glycol repeating units (claim 25).
Lee et al teach a glucagon derivative for treating metabolic syndrome, obesity, NASH, hypoglycemia (page 2, paragraph [8-9], pg. 3 [16]). They teach that a combined therapy capable of using various activity ratios by adjusting the contents of GLP-1 and glucagon may be more effective (pg. 3, [14]). Lee et al. teach a glucagon derivative having a general formula 2, SEQ ID NO: 46, (see [123]) which is identical to the formula 1 of the instant application. These polypeptides include the peptide of amino acid sequence of SEQ ID NO: 37 (see pg. 35, paragraph [501]). They teach making a long acting glucagon derivation by conjugating an immunoglobulin Fc region (see pg. 9 [155-156]). They teach that the linking moiety between an Fc and the glucagon derivative can be polyethylene glycol, wherein the PEG may be in the range of 1 kDa to 100 kDa (see page 26, [426-427]). They teach a pharmaceutical composition comprising a glucagon derivative comprises pharmaceutically acceptable excipient, carrier and/or diluent (see page 32 [466]). They teach administering the composition subcutaneously or by other route (see pg. 33, paragraph [471]). They teach administering another insulinotropic peptide such as GLP-1 receptor agonist selected from exendin-3, exendin-4, GLP-1 or a derivative thereof, wherein N-terminal histidine is substituted with one selected from desamino-histidyl, N-dimethyl-histidyl, beta-hydroxy imidazypropionyl, 4-imidazoacetyl, abd beta-carboxy imidazopropionyl, wherein the N-terminal amine group of exendin-4 is deleted or the N-terminal amine group of exendin-4 is substituted with a hydroxy group (see page 24, [406-409]). Lee et al do not teach treating chronic renal disease using a glucagon derivative and further comprising a GLP-1 receptor agonist.
Patel et al teach a method of treating kidney injury which in general lead to chronic kidney disease. They teach using chronic high fat diet fed C57BL/63 mice treated with streptozotocin to create renal dysfunction (Methods, pg. 80-81). They treated chronic diseased mice with GLP-1 and glucagon receptors co-agonist 150 ug/kg, subcutaneously (page 81, Methods). They teach that co-agonist treatment prevented worsening of renal dysfunction in high-fat diet fed mice (Results, pg. 83).
Parker et al teach treating chronic renal disease comprising administering a GLP-1/glucagon agonist (see abstract, claims 1-2, 29-30).
Therefore, it would have been prima facies obvious to one of ordinary skill in the art at the time the invention was made to use a glucagon derivative with or without a GLP-1 agonist because Patel et al Parker et al teach that dual agonist work better for treating chronic renal damage and Lee et al various glucagon derivatives that functionally work for treating diabetes. Additionally, one would have been motivated to do so because Patel et al and Parker et al. teach that co-agonist comprising glucagon and GLP-1 receptor agonist are able treat chronic damage to renal function or chronic renal disease. Further, one would have a reasonable expectation of success in using glucagon derivatives as taught by Lee et al in combination with a GLP-1 receptor agonist as taught by Lee et al for treating chronic renal disease as taught by Patel et al. or Parker et al. Therefore, the instantly claimed invention would have been obvious over the teachings prior art of record.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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