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
Applicants’ election without traverse of Group I (claims 1-12 and 14-18) drawn to a glucose-dependent insulinotropic polypeptide analog; and Applicants’ election of species without traverse: Peptide 7 (i.e., N-{ε-16}-18-{[(23R)-23-carboxyl-2,11,20-trioxo-10,19-diaza-4,7,13,16- tetraoxatricosyl-23-yl]amino}-18-oxooctadecanoic. acid acetyl-[Aib2, L14, R30]-hGIP(1-31)), in the reply filed on July 28, 2026 is acknowledged.
The species of group I, therefore claims 1-12 and 14-18 which read on the elected species has been considered.
Claims 1-12 and 14-18 are hereby examined on the merits.
Claims 13 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 28, 2026.
Priority
This application claims right of priority to foreign applications CN patent application No.
202211673990.6 filed December 26, 2022, and CN patent application No. 202311769474.8 filed on December 21, 2023.
Status of Claims
Claims 1-19 are pending. Claims 13 and 19 are withdrawn for further consideration.
Claims 1-12 and 14-18 are currently examined on the merits herein.
Information Disclosure Statement
The IDS was provided with the application.
Specification
I. The use of the term Kromsil, in the instant specification, which is a trade name or a mark used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms 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.
II. The amino acid sequence number in the specification is not represented in standard form. For example, protein sequence/amino acid sequence numbers should be represented as SEQ ID NO: 1.
Appropriate correction is required.
Claim Interpretation
The election of species of Peptide 7, i.e., SEQ IN NO: 7 conjugate (i.e., N-{ε-16}-18-{[(23R)-23-carboxyl-2,11,20-trioxo-10,19-diaza-4,7,13,16- tetraoxatricosyl-23-yl]amino}-18-oxooctadecanoic. acid acetyl-[Aib2, L14, R30]-hGIP(1-31)) read on claims 1-12 and 14-18.
BRI of claim 1, a glucose-dependent insulinotropic polypeptide (GIP) analog, comprising a GIP-like polypeptide segment, wherein the GIP-like polypeptide segment is: (a) YX2EGTFISDYSIX13X14DX16X17X18QX20X21FVX24WLLAQX3X31; wherein X2 is selected from A, D-Ala or Aib, X13 is selected from A or Aib, X14 is selected from M or L, X16 is selected from E, K or R, X17 is selected from I or L, X18 is selected from H or R, X20 is selected from K, E or Q, X21 is selected from D or E, X24 is selected from K or N, X30 is selected from K or R, and X31 is G or is absent; or (b) X2EGTFISDYSIX13X14DX16X17X18QX20X21FVX24WLLAQX30X31Y1.
According to the elected species, the polypeptide sequence analog refers to SEQ ID NO: 7 – YAibEGTFISDYSIALDKIHQQDFVNWLLAQRG.
Y1 may be selected from GPSSGAPPPS, KPSSGAPPPS, GPSSGAPPS, PSSGAPPPS, or PSSGAPPS.
BRI of claim 4, the long-acting conjugating component is connected to the GIP analog; and the long-acting conjugating component is selected from the group consisting of fatty acid side chains, polymers, cholesterols, albumins and segments thereof, albumin-binding substances, polymers of repeating units having specific amino acid sequences, antibodies, antibody segments, FcRn-binding substances, in vivo connective tissues, nucleotides, fibronectin, transferrin, saccharides, heparin, and elastin.
The election of species of long-acting conjugating component as N-{ε-16}-18-{[(23R)-23-carboxyl-2,11,20-trioxo-10,19-diaza-4,7,13,16- tetraoxatricosyl-23-yl]amino}-18-oxooctadecanoic. acid acetyl-[Aib2, L14, R30]-hGIP(1-31) reads on claim 4 and dependent claims.
BRI of claim 7, the long-acting conjugate of GIP analog, is selected based on the election of species -
PNG
media_image1.png
196
646
media_image1.png
Greyscale
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.
Claim 1 is 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 claims contain 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus.
Scope of the claims
The claims are drawn to a polypeptide segment having the function of the polypeptide segment as defined in (a) or (b); where (a) and (b) is directed to a glucose-dependent insulinotropic polypeptide (GIP) analog. The rejection stems from the limitation “function of the polypeptide segment,” which recites a feature by functional rather than structural language. There is nothing further in the claim to indicate the structural feature(s) (i.e., an amino acid sequence(s)) required to meet this functional limitation, and describing an invention by function is insufficient to meet the written description requirement.
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, several embodiments of the invention were reduced to practice: see Embodiment 1. The specification states that in particular, the amino acid sequences in (c) refer to: the amino acid sequences obtained by substitution, deletion or addition of one or more (specifically, possibly 1-50, 1-30, 1-20, 1-10, 1-5, or 1-3) amino acids from/onto the amino acid sequence as shown in Scheme (a) or (b); or the amino acid sequences obtained by addition of one or more amino acids (specifically, possibly 1-50, 1-30, 1- 20, 1-10, 1-5, or 1-3) amino acids at the N-terminus and/or C-terminus; and the polypeptide segments encoded by them have the function of the polypeptide segments as defined in Scheme (a) or (b), respectively (see CONTENTS OF THE INVENTION, page 2 last paragraph – page 3 first paragraph, page 3 Table). Although these variations are allowed by the claims, they are not represented in the reduction to practice. Thus, one cannot extrapolate how a polypeptide with 90% sequence identity to sequences in (a) and (b) scheme of claim 1 might impact its functionality.
Sufficient relevant identifying characteristic
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination thereof.
i. Complete structure:
As stated above, the complete structure of the peptides (see page 3, first paragraph, Table) are disclosed.
ii. Partial structure:
The specification states that as a partial structure the peptides must comprise GIP-like polypeptide segment. Page 3 Table discloses numerous polypeptides that meet this requirement but that in one embodiment, GIP polypeptide analogs are artificially designed and can generally be derived from naturally occurring GIP (see page 4, first paragraph). The active group of the side chain modification (active groups such as carboxylic acid groups from the aliphatic chains or PEGs, or a maleimide group, etc.) may react with the amino acid residue of the GIP-like polypeptide segment so as to undergo various types of condensation reactions (see page 4, third paragraph). Therefore, it is unclear from the partial structure which additional elements are necessary to meet all of the claimed properties of the genus.
iii. Physical and/or chemical properties:
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the polypeptide derivatives and therefore do not describe which substitutions, deletions or additions could be made while preserving this conformation. Understanding the physical basis for having glucose-dependent hypoglycemic effect is critical to determining which of the sequences that meet the sequence requirements of the genus also meet this additional functional requirement of the genus.
iv. Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification does not describe a general correlation between sequence and structural coordinates for the claimed genus. As a result, it is impossible to predict, based on the specification, how changing any position will affect the pharmaceutical efficacy.
v. Method of making the claim invention:
Solid state peptide synthesis and the cloning, recombinant expression and purification of proteins is well-known in the art. It is not disputed that one of ordinary skill in the art could isolate, albeit with route experimentation and optimization, a polypeptide of a given sequence provided that the sequence is known. Where the specification fails to provide description is in the structure of the polypeptide derivative to make. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless peptides that meet the sequence and modification requirements of the claims would also have specific structural conformation with hypoglycemic effect. Consequently, it is unknown whether all variants encompassed within the range of 90% sequence identity or polypeptide segment having the function of GIP-like polypeptide segments would retain the structural, chemical, and/or physical properties required to engage in agonistic activity at glucose-dependent insulinotropic polypeptide receptors to effectively enhance the hypoglycemic and weight loss effects. Therefore, the instant specification does not provide adequate written description to possess the broad genus described above since the specification does not disclose a correlation between the necessary structure of the sequence and the claimed function to be maintained.
Conclusion
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Claim Rejections - 35 USC § 103
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 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 1-12 and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over US 20190367578 (published December 5, 2019), in view of US 20160257729 (published September 8, 2016).
US’578 teaches novel peptides that are derivatives of glucose-dependent insulinotropic polypeptide (GIP) analogues having improved physical stability in solution and a protracted profile of action; such peptides that are agonists at the GIP receptor and to their use in weight management or for treatment of diseases such as obesity, diabetes or non-alcoholic steatohepatitis (NASH) (see Abstract). US’578 discloses a derivative of a GIP analogue comprising Formula I (SEQ ID NO: 3): (I) Tyr-Ala-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile- Ala-Met-Asp-Lys-Ile-His-Gln-Gln-Asp-Phe-Val-Lys-Trp-Leu-Leu-Ala-Gln-Lys-Gly, wherein a modifying group is covalently attached to the side chain of the epsilon amino group of the lysine at position 24, the modifying group being defined by A-B-C-, wherein A- is a lipophilic moiety with a negatively charged moiety at the distal end and B-C- is a linker; and wherein the GIP analogue has a maximum of 8 amino acid substitutions as compared to hGIP(1-31) (SEQ ID NO: 2), or a pharmaceutically acceptable salt, or amide thereof; comprising Formula II (SEQ ID NO: 48): (II) X1-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Ala-X14-Asp-X16-Ile-X18-Gln-X20-Asp-Phe-Val-Lys-Trp-Leu-Leu-Ala-Gln-Lys-X31, wherein Formula II comprises any amino acid at positions X1, X2, X14, X16, X18, X20, and/or X31; and wherein the GIP analogue has a maximum of 8 amino acid substitutions as compared to hGIP(1-31) (SEQ ID NO: 2); wherein the amino acids at positions X1, X2, X14, X16, X18, X20, and/or X31 are selected from (SEQ ID NO: 49): X1 is Tyr or D-Tyr; X2 is Aib, Ala, or D-Ala; X14 is Leu, Nle, Asp or Met; X16 is Lys or Ala; X18 is Arg or His; X20 is Gln, Glu or Aib; X31 is Gly or Pro. (see [0140]-[0155]).
US’578 is silent about addition/presence of the C-terminal moiety, Y1 (i.e.Y1 may be selected from GPSSGAPPPS, KPSSGAPPPS, GPSSGAPPS, PSSGAPPPS, or PSSGAPPS) in instantly claimed GIP-like polypeptide segment.
US’729 teaches about compounds which have agonist activity at the glucagon, GIP and GLP-1 receptors, and to their use in the treatment of metabolic disorders (see Abstract). US’729 discloses glucagon-GLP-1-GIP triple agonist compound having the general formula I:R1-Tyr-X2-Gln-Gly-Thr-Phe-Thr-Ser-Asp-X10-Ser-X12-X13-Leu-X15-X16-X17-Ala-X19-X20-X21-Phe-X23-X24-Trp-Leu-X27-X28-X29-X30-Y1-R2 (see claim 1); where the Y1 groups, when present, may provide increased stability in vivo, e.g. in serum, and so may contribute to the half-life of the GIP analogue (see [0027]). US’729 specifies the Y1 sequences Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser, Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser, Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser, Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser, Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser and Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser have homology with a C-terminal portion of the Exendin-4 molecule and appear to contribute to the stability of the molecule without concomitantly providing significant levels of GLP-1 agonist activity (see [0028]).
Examiner’s Note: It is known in the art about the use of exendin amino acid sequence as a C-terminal extension moiety for enhanced stability of glucagon or glucagon analog sequences. See Chabenne et. al.
At the time before the effective filling date of the claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of US’578 and US’729 before the effective filing date of the claimed invention by addition/extension of GIP analog (as taught by US’578) with an exendin-based C-terminal sequence (as taught by US’729) to enhance stability and solubility of the GIP analog at physiological pH. One of ordinary skill in the art would have been motivated to utilize the C-terminus moiety as taught by US’729 as these moiety/groups may help to stabilize the three dimensional conformation of the molecule and/or provide resistance to proteolytic degradation (see US’729, [0027] added to glucose-dependent insulinotropic polypeptide (GIP) analogues for improved physical stability (see US’578, [0002], [00016]) with a reasonable expectation of success for prevention and/or treatment of all forms of diabetes, such as hyperglycemia, type 2 diabetes, diabetes related metabolic syndrome, and/or obesity (see US’578 [0130]-[0135]).
Regarding claim 1: The GIP analog polypeptide sequence disclosed by US’578, i.e., (SEQ ID NO: 2), or a pharmaceutically acceptable salt, or amide thereof; the derivative comprising Formula II (SEQ ID NO: 48):X1-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Ala-X14-Asp-X16-Ile-X18-Gln-X20-Asp-Phe-Val-Lys-Trp-Leu-Leu-Ala-Gln-Lys-X31, wherein Formula II comprises any amino acid at positions X1, X2, X14, X16, X18, X20, and/or X31; wherein the GIP analogue has a maximum of 8 amino acid substitutions as compared to hGIP(1-31) (SEQ ID NO: 2); and wherein the amino acids at positions X1, X2, X14, X16, X18, X20, and/or X31 are selected from
X1 is Tyr or D-Tyr; X2 is Aib, Ala, or D-Ala; X14 is Leu, Nle, Asp or Met; X16 is Lys or Ala; X18 is Arg or His; X20 is Gln, Glu or Aib; and X31 is Gly or Pro (see US’578 claim 1 and [0143]-[0155]). Additionally, US’729 discloses a glucagon-GLP-1-GIP triple agonist compound having the general formula I with a C-terminal Y1, where Y1 is s Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser, Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser, Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser, Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser, Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser or Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser (see US’729 claim 1).
Regarding claim 2: As taught above, SEQ ID NO: 2 of US’578 is similar to the instantly claimed GIP analog an amino acid sequence.
Regarding claims 3-7: US’578 discloses a GIP analogue derivative comprising a GIP analogue and a modifying group, wherein the GIP analogue is (SEQ ID NO: 48) X1-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile- Ala-X14-Asp-X16-Ile-X18-Gln-X20-Asp-Phe-Val- Lys-Trp-Leu-Leu-Ala-Gln-Lys-X31; wherein X1 is Tyr, Ac-Tyr, or Ac-D-Tyr; X2 is Aib or Ala; X14 is Nle; X16 is Lys; X18 is Arg or His; X20 is Gln or Aib; and X31 is Gly or Pro; wherein the modifying group is covalently attached to the GIP analogue at the side chain of the epsilon amino group of the lysine at position 24; or a pharmaceutically acceptable salt or amide thereof (see claim 1). US’578 specifies the derivative, wherein the GIP analogue, wherein the modifying group is A - B - C- , wherein A- is a lipophilic moiety with a negatively charged moiety at the distal end and B - C - is a linker comprising at least one negatively charged moiety (see [0196]-[0197]).
PNG
media_image2.png
202
620
media_image2.png
Greyscale
The modifying group (see “Chem. 15” above) disclosed by US’578 is identical to the GIP analog conjugate set forth by the instantly claimed compound species (see instant claim 7).
Additionally, US’578 teaches the derivative has improved physical stability in solution (see [0101]); the derivatives have improved chemical stability (see [0109]).
Therefore, at the time before the effective filling date of the claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to use the method for GIP analogue derivative comprising a GIP analogue and a modifying group as taught by US’578, may be appropriately modified by using the conjugate/modifying group (Chem 15) covalently attached to the GIP analogue at the side chain of the epsilon amino group of the lysine at position 24 as taught by US’578 along with the C-terminal exendin-homologous (Y1) moiety as taught by US’729, to arrive at the presently claimed invention. The artisan of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in synthesizing GIP analog modified to long-acting conjugates to improve pharmacokinetic properties such as increased terminal half-life; increasing terminal half-life the compound is eliminated slower from the body; thus the derivatives entails an extended duration of pharmacological effect (see US’729 [0088]-[0089]).
Regarding claim 8: US’578 teaches derivatives of GIP analogues that are capable of activating the GIP receptor (see [0013]); in a further aspect, the derivatives of GIP analogues are selective at activating the human GIP receptor over the human GLP-1 receptor and the human glucagon receptor (see [0013]). US’578 specifies the term “selective” for the GIP receptor over the GLP-1 receptor and glucagon receptor refer to derivatives that display at least 10 fold, such as at least 50 fold, at least 500 fold, or at least 1000 fold higher potency for the GIP receptor over the GLP-1 receptor and glucagon receptor (see [0022]).
Regarding claim 9: US’578 discloses GIP analogue derivative comprising a GIP analogue and a modifying group, wherein the modifying group is covalently attached to the GIP analogue at the side chain of the epsilon amino group of the lysine at position 24; or a pharmaceutically acceptable salt or amide thereof (see claim 1). US’578 specifies the derivatives of GIP analogues relates to pharmaceutical compositions comprising such derivatives of GIP analogues and pharmaceutically acceptable excipients, as well as the medical use of said derivatives (see [0012]).
Regarding claim 10: UD’578 teaches injectable compositions comprising derivatives that can be prepared using the conventional techniques of the pharmaceutical industry which involve dissolving and mixing the ingredients as appropriate to give the desired end product; is dissolved in a suitable buffer at a suitable pH so precipitation is minimised or avoided; and the injectable composition is made sterile, for example, by sterile filtration (see [0119]). US’578 exemplifies intravenous injections GIP derivatives compounds were given through one catheter (see [0653]).
Regarding claim 11: The pharmacokinetics profile disclosed by US’578 says the derivatives have improved pharmacokinetic properties such as increased terminal half-life (see [0089]); increasing terminal half-life means that the compound is eliminated slower from the body; for the derivatives this entails an extended duration of pharmacological effect (see [0089]).
Regarding claim 12: US’578 discloses a pharmaceutical composition comprising a GIP analogue derivative and a GLP-1 receptor agonist (see claim 6); wherein the GLP-1 receptor agonist is semaglutide (see claim 11). US’578 specifies derivatives of GIP analogues that are active in vivo alone or in combination with a GLP-1 receptor agonist (see [ 0014]); they have an in vivo effect on body weight, food intake and glucose tolerance both alone and in combination with a GLP-1 receptor agonist (see [0074].
Regarding claim 14: US’578 exemplifies the derivatives of the present invention all display good GIP potency and substantially no activity or no measurable activity at the human GLP-1 receptor and the human glucagon receptor (see [0648]).
Regarding claim 15: US’578 discloses GIP analogue derivative comprising a GIP analogue and a modifying group, wherein the modifying group is covalently attached to the GIP analogue at the side chain of the epsilon amino group of the lysine at position 24; or a pharmaceutically acceptable salt or amide thereof (see claim 1). US’578 specifies the derivatives of GIP analogues relates to pharmaceutical compositions comprising such derivatives of GIP analogues and pharmaceutically acceptable excipients, as well as the medical use of said derivatives (see [0012]). US’578 teaches the tested GIP derivatives have very long half-lives as compared to the half-life of hGIP(1-42) measured in man (see Table 2, [0656]).
Regarding claim 16: US’578 tested the pharmacokinetic properties of the derivatives, and in such studies, animals are typically administered with a single dose of the drug, either intravenously (i.v.), subcutaneously (s.c.), or orally (p.o.) in a relevant formulation (see [0091]-[0092]).
Regarding claim 17: US’578 provided Pharmacokinetics Profile—Half-Life In Vivo (see [0096]); the derivatives have improved pharmacokinetic properties (see [0097]); in a particular embodiment, the pharmacokinetic properties may be determined as terminal half-life (t1/2) in vivo in minipigs after i.v. administration, (see [0098], Example 3); in particular embodiments, the terminal half-life in minipigs is at least 24 hours, preferably at least 40 hours, even more preferably at least 60 hours (see [0099]). US’578 further teaches the derivative has improved physical stability in solution (see [0101]); the derivatives have improved chemical stability (see [0109]).
Regarding claim 18: Regarding pharmaceutical composition, US’578 discloses The treatment with a derivative according to the present invention may also be combined with one or more additional pharmacologically active substances, e.g. selected from GLP-1 receptor agonists, or GLP-1/glucagon receptor co-agonists (see [0124]); examples of GLP-1 receptor agonists to be combined with the derivative of the present invention are semaglutide… Semaglutide is a GLP-1 receptor agonist that may be prepared (see [0126]).
Regarding claims 14-18, it would have been obvious to combine the teachings of US’578 and US’729 before the effective filing date of the claimed invention to modify GIP analogue at the side chain of the epsilon amino group of the lysine at position 24 as taught by US’578 along with the C-terminal exendin-homologous (Y1) moiety as taught by US’729, to arrive at the presently claimed invention. The artisan of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in synthesizing GIP analog modified to long-acting conjugates to improve physical stability in solution (see US’578 [0101]); with improved chemical stability (see US’578 [0109]); along with enhanced pharmacokinetic properties such as increased terminal half-life; increasing terminal half-life the compound is eliminated slower from the body; thus the derivatives entails an extended duration of pharmacological effect (see US’729 [0088]-[0089]).
Therefore, the presently claimed invention was prima facie obvious to one of ordinary skill in the art at the time of the effective filling date.
Prior Art of Record
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chabenne et. al. (“Optimization of the Native Glucagon Sequence for Medicinal Purposes”; Joseph R. Chabenne, Maria A. DiMarchi, Vasily M. Gelfanov, and Richard D. DiMarchi; J Diabetes Sci Technol 2010; 4(6):1322-1331; published November 2010) teaches C-terminal extension (Cex) of glucagon analogs with an exendin-based, 10-residue, C-terminal sequence yielded a peptide of dramatically enhanced solubility (see Abstract). Chabenne et. al. prepared an analog of glucagon that extended the C-terminus from the native sequence through the added Cex (G P S S G A P P P S) (see page 1327, left col, paragraph 2, and sequence in the third row). Chabenne et. al. teaches the C-terminal extension (Cex) of the hormone with an exendin-based, 10-residue, C-terminal sequence yielded a peptide of dramatically enhanced solubility (see Results/Abstract).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KOYELI BANERJEE whose telephone number is (571)272-5751. The examiner can normally be reached Monday-Friday 8-4PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at (571) 270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KOYELI BANERJEE/Examiner, Art Unit 1658
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
Prosecution Insights