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 .
Nucleotide and/or Amino Acid Sequence Disclosures
The amendments filed January 23, 2026, place the application in compliance with the sequence rules.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Receipt is acknowledged of the certified translation of Chinese application No. 202011437565.8.
The earliest effective filing date of claims 1-9 is December 10, 2020.
Duplicate Claims
Applicant is advised that should claim 2 be found allowable, claim 3 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 102 - withdrawn
The rejection of claims 1-3, 6, and 8-9 under 35 U.S.C. 102(a)(2) as being anticipated by Clemmensen et al. (US 2023/0183335 A1) is withdrawn.
The earliest effective filing date of claims 1-9 is December 10, 2020.
Clemmensen et al. was published after the earliest effective filing date of the claims on June 15, 2023, and is therefore not prior art under 35 U.S.C. 102(a)(1).
Clemmensen et al. is the pre-grant publication of US Application No. 17/925, 818, which is the national stage application of PCT/EP2021/064930, filed June 3, 2021, which is after the earliest effective filing date of the instant claims.
PCT/EP2021/064930 claims priority to EP 20178057.4, filed June 3, 2020. Applicant filed a copy of this application in the response filed January 23, 2026 (see Appendix A). The European application does not disclose the subject matter relied upon in the rejection, SEQ ID NO: 9.
Therefore, the effective filing date of Clemmensen et al. is after the effective filing date of the instant claims, disqualifying Clemmensen et al. as prior art under 35 U.S.C. 102(a)(2).
Claim Rejections - 35 USC § 103 - withdrawn
The rejection of claims 4-5 and 7 under 35 U.S.C. 103 as being unpatentable over Clemmensen et al. (US 2023/0183335 A1), as applied to claims 1-3, 6, and 8-9 above, in further view of Huang (WO 2019/101042 A1; English language equivalent US 2021/0070829 A1) is withdrawn because Clemmensen et al. is not prior art under 35 U.S.C. 102(a)(2).
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 pre-AIA 35 U.S.C. 103(a) 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 1-3, 6, and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Just et al. (US 2015/0299281 A1) in view of Mathiesen et al. (Int. J. Mol. Sci. 2019, 20, 4092), Bastin et al. (Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2019:12 1973–1985), Manandhar et al. (J. Med. Chem. 2015, 58, 1020−1037), Jose et al. (Patient Preference and Adherence 2010:4 313–324), Adelhorst et al. (J Biol Chem 1994 269(9) 6275-6278).
Determining the scope and contents of the prior art.
Just et al. teach GIP-GLP1 dual receptor agonists that are useful therapies for type 2 diabetes mellitus, obesity, and related disorders (para. [0005], [0115]). Just et al. teach the genus of general Formula I, which includes the total scope of instant general formula I (claimed amino acids taught by the prior art are indicated in bold in table below). In addition, Just et al. teach a subgenus and species that are closely related to the claimed genus (claimed amino acids taught by the prior art are indicated in bold in table below). All of the species disclosed by Just et al. exhibit GIP and GLP1 receptor activity (Example 2, Table 3) and are taught to be suitable for therapeutic use in the treatment of type 2 diabetes mellitus, obesity, and related disorders (para. [0005], [0115]; claims 25-27, 44-46, 49-56).
Claimed
Formula I
Just et al. Genus
Formula I ¶ [0007]
Just et al.
Closest Subgenus
Formula II(a)’ ¶ [0026]
Just et al.
Closest Species
Compound 28, Table 2, SEQ ID NO: 30
Relevant teaching of Just et al. regarding structure-activity and position preferences.
1
Y
H, Y
Y
Y
All 56 species in Tables 1 and 2 have Y at position 1.
2
G
A, Aib, G
Aib, G
Aib
This position is vulnerable to DPP-IV cleavage. Aib contributes to resistance (¶ [0041]).
Compound 7 has G at position 2; 54 of 56 species in Tables 1 and 2 have Aib at position 2.
3
E
E, D
E
E
All 56 species in Tables 1 and 2 have E at position 3.
4
G
G
G
G
The prior art genus is identical to the claimed genus at this position.
5
T
T
T
T
The prior art genus is identical to the claimed genus at this position.
6
F
F
F
F
The prior art genus is identical to the claimed genus at this position.
7
T
T, S, I
T, S, I
T
A small polar residue (e.g. Thr or Ser) at position 7 may increase potency and/or selectivity at the GLP-1 receptor (¶ [0036]).
T is preferred at position 7 (¶ [0043]).
54 of 56 species in Tables 1 and 2 have T at position 7.
8
S
S
S
S
The prior art genus is identical to the claimed genus at this position.
9
D
D, E
D
D
All 56 species in Tables 1 and 2 have D at position 9.
10
Y
Y, L, S
Y, L
Y
54 of 56 species in Tables 1 and 2 have Y at position 10.
11
S
S, L
S, L
S
54 of 56 species in Tables 1 and 2 have S at position 11.
12
I
I
I
I
The prior art genus is identical to the claimed genus at this position.
13
Y
A, Y, Aib
A, Y, Aib
Y
50 of 56 species in Tables 1 and 2 have Y at position 13.
14
L
M, L, S
L
L
A hydrophobic residue like leucine at position 14 enhances GLP-1R activity, increases potency and/or selectivity at GLP-1R, and increases chemical stability by reducing potential for oxidation (¶ [0043]).
55 of 56 species in Tables 1 and 2 have L at position 14.
15
D
D, E
D, E
D
45 of 56 species in Tables 1 and 2 have D at position 15. The rest have the conservative substitution E.
16
K
K, G, S, E
K, S, E
K
37 of 56 species in Tables 1 and 2 have K at position 16.
17
Q
I, K, Q, R, E
K
K
Most species in Tables 1 and 2 have K at position 17.
18
A
A
A
A
The prior art genus is identical to the claimed genus at this position.
A small hydrophobic residue (e.g. Ala) at position increases potency and/or selectivity at the GLP-1R (¶ [0038]).
19
AKE or QRA
Q, A, E, K
Q, A, E, K
Q
A or Q are preferred (¶ [0043]).
36 of 56 species in Tables 1 and 2 have AKE or QRA at positions 19-21. The rest have the conservative substitutions.
20
Q, K, R
Q, K, R
R
36 of 56 species in Tables 1 and 2 have AKE or QRA at positions 19-21.
21
D, A, E
D, A, E
A
A is preferred (¶ [0043]).
36 of 56 species in Tables 1 and 2 have AKE or QRA at positions 19-21.
22
F
F, 1-Nal
F
F
All 56 species in Tables 1 and 2 have F at position 22.
23
V
V, I, L
V, I
V
53 of the 56 species in Tables 1 and 2 have V at position 23. The rest have conservative substitution I.
24
N or E
N, E, R, K
N, E, K
N
All 56 species in Tables 1 and 2 have N or E at position 24.
25
W
W
W
W
The prior art genus is identical to the claimed genus at this position.
26
L
L
L
L
The prior art genus is identical to the claimed genus at this position.
27
L
L, V, I, K, E, S
L, V, I, E
L
L is preferred (¶ [0043]).
47 out of 56 species in Tables 1 and 2 have L at position 27.
28
A
A, S, R, Aib
A, S, R, Aib
A
34 out of 56 species in Tables 1 and 2 have A at position 28.
29
G or Q
Q, Aib, E, K, G, Y
Q, Aib, A, G
Aib
Compounds 1, 4, 30, and 33 have a Q at position 29. Most species in Tables 1 and 2 have Aib.
30
G
K, G, P, absent
K, G, absent
G
The addition of GPSSGAPPPS, GPSSGAPPS, PSSGAPPPS, PSSGAPPS at or after position 29 or at or after position 30 increases GLP1R activity (¶ [0040]).
Compounds 2, 28, 32, 33, 53, 54, 55 have GPSSGAPPPS at positions 30-39.
31
P
G, P, S, E, absent
GPSSGAPPPS, GPSSGAPPS, PSSGAPPPS, PSSGAPPS, absent
P
32
S
K, S, absent
S
33
S
K, S, E, absent
S
34
G
N, G, A, K, absent
G
35
A
D, A, P, E, absent
A
36
P
W, P, K, absent
P
37
P
K, P, E, absent
P
38
P
H, P, S, K, absent
P
39
S
N, S, absent
S
40
I, absent
41
T, absent
42
Q, absent
Ascertaining the differences between the prior art and the claims at issue.
Although Just et al. teach a genus that encompasses the full scope of instant formula I, it does not teach a subgenus that is the same as the claimed genus or a single species that falls within the claimed genus. See claim map above.
The differences between Just et al. and instant claim 1 are at three positions:
1) at position 2, the prior art allows the claimed glycine but predominantly teaches Aib;
2) at position 17, the prior art allows the claimed glutamine but predominantly teaches lysine; and 3) at position 29, the prior art allows the claimed glycine or glutamine but predominantly teaches Aib.
Resolving the level of ordinary skill in the pertinent art.
The structure-activity of GIP and GLP1 peptides has been studied extensively in the prior art (See e.g. Mathiesen et al., Manandhar et al., Bastin et al.).
Bastin et al. review the development of dual GIPR-GLP1R coagonists as therapies for obesity and type 2 diabetes including LY3298176 (aka tirzepatide) and RG7697/NNC0090-2746. Both peptides were developed by mixing residues responsible for GIPR and GLP1R activity (Figure 1) and are in clinical development or use. RG7697/NNC0090-2746 is closely related to the claimed formula I, differing only at positions 2 and 20 (Figure 2):
PNG
media_image1.png
317
656
media_image1.png
Greyscale
Like Just et al., Bastin et al. teach that position 2 is vulnerable to DPP-IV cleavage and presents Aib as a solution to this problem. In addition, RG7697/NNC0090-2746 contains the glutamine at position 17 and the glycine at position 29 required by the instant claims and allowed but not reduced to practice by Just et al.
Manandhar et al. disclose a structure-activity relationship for GLP1:
PNG
media_image2.png
170
625
media_image2.png
Greyscale
Notably, Manandhar et al. corroborate the importance of position 2 for DPP-IV cleavage. In addition, Manandhar et al. teach that GLP1 contains glutamine at position 17, which functions as a linker region between the N- and C-terminal helices, and a glycine at position 29.
Jose et al. review the clinical use of exenatide, an incretin (GLP1) mimic (p. 315, col 1, emphasis added): “Exenatide, a synthetic version of the naturally occurring salivary peptide isolated from the Gila monster (Heloderma suspectum), is a partial structural analog of human GLP-1 and has 53% amino acid sequence homology with human GLP-1. It contains a glycine at position 2, in contrast to human GLP-1, which has an alanine at position 2, thus making the molecule DPP-4 resistant, in turn conferring a longer half-life. Exenatide has a half-life of 3.3–4.0 hours and clinical effects lasting for up to 8 hours. Exenatide treatment results in significant reductions in fasting plasma glucose (FPG) and post-prandial glucose (PPG) in patients with T2DM.48–51 In addition, it results in slowing of gastric emptying (which contributes to the reductions in PPG), appetite suppression and weight loss.” Like Just et al., Bastin et al. and Manandhar et al., Jose et al. confirm the importance of position 2 for DPP-IV cleavage. In addition, Jose et al. teach that glycine at position 2, like the Aib taught by Just et al. and Bastin et al., reduces DPP-IV cleavage and extends the half-life of the peptide.
Adelhorst et al. teach that replacing the glutamine at position 17 of GLP1 with alanine (reference uses numbering Gln23) slightly lowered the affinity and activity (IC50: 0.27 nM→1.1 nM; EC50: 2.6 nM→5 nM).
Adelhorst et al. teach that replacing the glycine at position 29 of GLP1 with alanine (reference uses numbering Gly35) slightly lowered the affinity and increased activity (IC50: 0.27 nM→1.3 nM; EC50: 2.6 nM→1 nM).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The specification compares the claimed peptides to dulaglutide but fails to provide a comparison to the close prior art of Just et al. (species Compound 28) or Bastin et al. (species RG7697/NNC0090-2746).
Dulaglutide contains more differences relative to the claimed formula I than either Just et al. or Bastin et al. See the structure in Figure 1 of Anderson et al.
PNG
media_image3.png
596
1152
media_image3.png
Greyscale
which shows differences at positions 1, 10, 12, 15, 16, 23, 24, 27, 28, 31-33, and 35-39.
Therefore, there is no evidence on record establishing that the claimed peptides have unexpected properties.
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to prepare the peptides of Just et al., including Compound 28 and subgenus Formula II(a)’, with glycine at position 2, glutamine at position 17, and glycine or glutamine at position 29, thereby satisfying the limitations of claim 1. The rationale for obviousness is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention (MPEP § 2143.01(G)). The relevant findings for this rationale are as follows.
(1) There was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings. 1) Regarding position 2, the prior art of Just et al., Bastin et al., Manandhar et al., and Jose et al. all teach that position 2 is vulnerable to DPP-IV cleavage, which has the effect of shortening the half-life of the GLP1 or GLP1/GIP dual agonist. Whereas Just et al., Bastin et al., and Manandhar et al. focus on Aib at position 2 to increase DPP-IV resistance, Jose et al. teach that glycine at position has the same effect in the GLP1 mimic exanatide. Therefore, it would have been obvious to select glycine from the options for position 2 taught by Just et al. in order to increase DPP-IV resistance in the manner taught by Jose et al. 2) Regarding position 17, Bastin et al. teach that RG7697/NNC0090-2746, a therapeutically active GLP1/GIP dual agonist contains glutamine at position 17. Manandhar et al. teach that GLP1 contains glutamine at position 17, which functions as a linker region. Adelhorst et al. teach that replacing the glutamine at position 17 of GLP1 with alanine (reference uses numbering Gln23) slightly lowered the affinity and activity (IC50: 0.27 nM→1.1 nM; EC50: 2.6 nM→5 nM). Therefore, it would have been obvious to select glutamine from the options for position 17 taught by Just et al. in order to maintain the structure of GLP1 at this position taught by Manandhar et al. and the GLP1R affinity and activity taught by Adelhorst et al. 3) Regarding position 29, Bastin et al. teach that RG7697/NNC0090-2746, a therapeutically active GLP1/GIP dual agonist contains glycine at position 29. Manandhar et al. teach that GLP1 contains glycine at position 29. Adelhorst et al. teach that replacing the glycine at position 29 of GLP1 with alanine (reference uses numbering Gly35) slightly lowered the affinity (IC50: 0.27 nM→1.3 nM). Therefore, it would have been obvious to select glycine from the options for position 29 taught by Just et al. in order to maintain the structure of GLP1 at this position taught by Manandhar et al. and the GLP1R affinity taught by Adelhorst et al.
(2) There was reasonable expectation of success. One of ordinary skill in the art would predict that the peptides of Just et al., including Compound 28 and subgenus Formula II(a)’, with glycine at position 2, glutamine at position 17, and glycine or glutamine at position 29 would function as dual GLP1/GIP agonists because teach Just et al. teach that these amino acids are permitted at these positions in the disclosed genus taught to be useful for this purpose. Just et al. teach that Compound 7, which has a glycine at position 2, is active in a GIPR and GLP1R assay (Table 3). Just et al. teach that compounds 1, 4, 30, and 33, which have a glutamine at position 29, are active in a GIPR and GLP1R assay (Table 3). In addition, Jose et al. teach that exanatide, a therapeutically active GLP1 agonist, contains glycine at position 2. In addition, Bastin et al. teach that RG7697/NNC0090-2746, a therapeutically active GLP1/GIP dual agonist contains glutamine at position 17 and glycine at position 29. Therefore, there was a reasonable expectation of success.
(3) Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. There is no evidence on record establishing that the claimed peptides have unexpected properties.
The rationale to support a conclusion that the claim would have been obvious is that "a person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). Therefore, claim 1 is obvious over the cited art.
Regarding claims 2 and 3, a peptide identical to Compound 28 of Just et al. modified with glycine at position 2, glutamine at position 17, and glycine at position 29, would be identical to instant SEQ ID NO: 1 except that the positions 19-21 would be QRA instead of AKE. This difference is not significant given that Just et al. teach that AKE and QRA are alternatives at these positions (Tables 1 and 2). A peptide identical to Compound 28 of Just et al. modified with glycine at position 2, glutamine at position 17, and glycine at position 29, would be identical to instant SEQ ID NO: 2 except that the position 24 would be E instead of N. This difference is not significant given that Just et al. teach that E and N are alternatives at these positions (Tables 1 and 2).
Regarding claim 6, Just et al. teach GIP-GLP1 dual receptor agonists that are useful therapies for type 2 diabetes mellitus, obesity, and related disorders and have a blood glucose lowering effect (para. [0005], [0115]).
Regarding claim 8, Just et al. teach GLP1R agonist activity (Table 3).
Regarding claim 9, Just et al. teach GIPR agonist activity (Table 3).
Claims 4-5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Just et al. (US 2015/0299281 A1) in view of Mathiesen et al. (Int. J. Mol. Sci. 2019, 20, 4092), Bastin et al. (Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2019:12 1973–1985), Manandhar et al. (J. Med. Chem. 2015, 58, 1020−1037), Jose et al. (Patient Preference and Adherence 2010:4 313–324), and Adelhorst et al. (J Biol Chem 1994 269(9) 6275-6278), as applied to claims 1-3, 6, and 8-9 above, in further view of Huang (WO 2019/101042 A1; English language equivalent US 2021/0070829 A1).
Peptides of instant formula I and comprising instant SEQ ID NOs: 1 and 2 are obvious over Just et al., Mathiesen et al., Bastin et al., Manandhar et al., Jose et al., and Adelhorst et al. for the reasons presented above.
Neither Just et al., Mathiesen et al., Bastin et al., Manandhar et al., Jose et al., nor Adelhorst et al. teach that the peptide is fused to non-functional area for increasing protein stability to yield instant SEQ ID NO: 3 or 4.
Huang teaches a multi-domain active protein for treating metabolic and related diseases and preparation and application thereof. The polyagonist proteins have a significant effect in weight loss, and can be used in the clinical treatment of diabetes, obesity, non-alcoholic fatty liver disease, hyperlipidemia and other related diseases (¶ [0012]). The multi-domain active proteins include a structure shown in Formula I: A-La-F-Lb-B wherein A is a GCGR/GLP-1R dual-agonist peptide, F is a long-acting protein unit, B is a native FGF21 or FGF21 analogue, La does not exist or is a peptide linker, and Lb does not exist or is a peptide linker (¶ [0014]). The multi-domain active protein combines GLP-1, GCG and FGF21 agonism (¶ [0015]).
It would have been obvious to substitute the GIP/GLP-1R dual-agonist peptide identical to SEQ ID NO: 1 or 2 that is obvious over Just et al. for variable A in the multi-domain active protein taught by Huang. One of ordinary skill in the art would have been motivated to do so in order to extend the half-life of the GIP/GLP-1R dual agonist peptide by fusing it to F as taught by Huang, and in order to combine the GIP/GLP-1R dual agonist activity with the FGF21 agonist activity taught by Huang. There would have been a reasonable expectation of success given that both references are directed to the treatment of diabetes, obesity, non-alcoholic fatty liver disease, hyperlipidemia and other related diseases.
Regarding claim 4, numerous embodiments reduced to practice by Huang are identical to instant SEQ ID NOs: 3 and 4 at the position corresponding to 40 to the C-terminal, including SEQ ID NOs: 106, 154, 160, 166, 181, 193, and 338. See for example the alignment between instant SEQ ID NO: 4 and prior art SEQ ID NO: 338:
Qy 1 YGEGTFTSDYSIYLDKQAQRAFVEWLLAQGPSSGAPPPSGGGGSGGGGSGGGGSAESKYG 60
: :|||||||| ||| || : ||:||: |||||||||||||||||||||||||||||||
Db 1 HSQGTFTSDYSKYLDSQAAQDFVQWLMNGGPSSGAPPPSGGGGSGGGGSGGGGSAESKYG 60
Qy 61 PPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVE 120
Qy 121 VHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP 180
Qy 181 REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS 240
Qy 241 FFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG 283
|||||||||||||||||||||||||||||||||||||||||||
Db 241 FFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG 283
Therefore, substituting the peptide identical to instant SEQ ID NO: 1 or 2 that is obvious over Just et al. for the reasons presented above for the region corresponding to A in the prior art will yield peptides comprising instant SEQ ID NOs: 3 and 4.
Regarding claim 5, Huang teaches pharmaceutical compositions comprising the proteins (¶ [0043]).
Regarding claim 7, Huang teaches pharmaceutical compositions for blood glucose lowering comprising the proteins (¶ [0062]).
Response to the Arguments
Applicant's arguments filed January 23, 2026, have been fully considered but they are not persuasive.
Applicant traverses the rejection on the grounds that the primary reference Just et al. emphasizes the non-natural amino acid Aib at positions 2 and 29, in combination with lysine at position 17, and which differs from the claimed peptides. Applicant traverses the rejection on the grounds that the secondary reference Manandhar et al. discloses GLP-1 mimics that are distinct from the dual agonists of the primary reference and of the claimed invention, and does not compare glutamine to lysine at position 17 or glycine to Aib at position 29. Applicant traverses the rejection on the grounds that the secondary reference Bastin et al., which discloses glutamine at position 17 and glycine at position 29, also discloses Aib at position 2. Applicant traverses the rejection on the grounds that the secondary reference Jose discloses GLP-1 mimics that are distinct from the dual agonists of the primary reference and of the claimed invention, and does not compare glycine to Aib at position 2. Applicant also argues that the secondary reference of Adelhorst et al. underscores the sensitivity and unpredictability of residue substitutions. Applicant argues that because of these deficiencies, the rejection is based on hindsight reasoning and fails to establish a reasonable expectation of success.
In response, it is important to note that the primary reference teaches a genus that includes the claimed general formula I and the species SEQ ID NOs: 1-4. That is considering the three differences between the primary reference and the claims, the prior art allows for the claimed amino acid at each position: 1) at position 2, the primary reference allows the claimed glycine; 2) at position 17, the primary reference allows the claimed glutamine; and 3) at position 29, the primary reference allows the claimed glycine or glutamine. Therefore, there is an expectation of success in Just et al. that selecting glycine at position 2, glutamine at position 17, and glycine or glutamine at position 29 will result in peptides that function as GIP-GLP1 dual receptor agonists. One of ordinary skill in the art would expect that peptides having glycine at position 2, glutamine at position 17, and glycine or glutamine at position 29 will function as GIP-GLP1 dual receptor agonists because Just et al. teach this fact.
The cited art is consistent in acknowledging the vulnerability of position 2 to DPP-IV cleavage and the associated effect of a short half-life for the peptide. Just et al. teach that both Aib and Gly are options at this position to protect against DPP-IV cleavage, although it is true that Aib is preferred, consistent with Bastin et al. and Manandhar et al. Although Aib is preferred, Just et al. reduce to practice a peptide with glycine at position 2, Compound 7, and demonstrate that it is active in a GIPR and GLP1R assay (Table 3). Jose et al. show that in related peptides, Gly protects against DPP-IV cleavage, which is consistent with the teaching of Just et al. that Gly can serve this purpose at position 2 and further supports selection of Gly at this position.
The cited art is consistent in acknowledging that position 17 can be glutamine. As stated above, the primary reference allows for position 17 to be glutamine, establishing an expectation of success for choosing glutamine at this position. Bastin et al. corroborate this choice by showing that RG7697/NNC0090-2746, a therapeutically active GLP1/GIP dual agonist contains glutamine at position 17. Manandhar et al. also corroborate this choice by teaching that in GLP1, the glutamine at position 17 functions as a linker. Adelhorst et al. also corroborate this choice by teaching that GLP1 receptor affinity and activity are lowered when glutamine at position 17 is substituted. Together these references suggest that glutamine at position will preserve function of the peptides as GIP-GLP1 dual receptor agonists.
The cited art is consistent in acknowledging that position 29 can be glycine or glutamine. As stated above, the primary reference allows for position 29 to be glycine or glutamine, establishing an expectation of success for choosing glycine or glutamine at this position. Bastin et al. corroborate this choice by showing that RG7697/NNC0090-2746, a therapeutically active GLP1/GIP dual agonist contains glycine at position 29. Together these references suggest that glycine or glutamine at position will preserve function of the peptides as GIP-GLP1 dual receptor agonists.
There is no data on record that established that the claimed peptides have properties that are unexpected in view of the prior art. In contrast, the data in the specification is consistent with the expectation set by Just et al. that the peptides have GIP-GLP1 dual receptor agonist activity.
For these reasons, the rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
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, Lianko G Garyu can be reached at (571) 270-7367. 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.
/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654