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 .
Priority
The instant application claims priority to 371 National Stage Application PCT/EP2022/074607, filed September 5th, 2022, and foreign application EP21315153.3, filed September 6th, 2021, under 35 U.S.C. 119(a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The priority date of September 6th, 2021 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) filed on October 31st, 2024 and March 23rd, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is considered by the examiner.
Claims Status
The claim listing filed on August 7th, 2026 is pending. Claims 1-19 are being examined on the merits in this office action.
Claim Objections
Claim 19 is objected to because of the following informalities: the recitation “for use as a pharmaceutical” is redundant. The preamble already makes clear that the composition is pharmaceutical. Appropriate correction is required.
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 12 is 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 shortening the duration, ameliorating, slowing down, inhibiting progression or worsening, and prevention of type 2 diabetes, does not reasonably provide enablement for the complete scope of treating type 2 diabetes. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The breadth of claim 12 encompasses using a compound of formula I to cure type 2 diabetes. Applicant’s lexicography alters the scope of “treating/treatment of a disease or disorder" to include curing, shortening the duration, ameliorating, slowing down or inhibiting progression or worsening of a disease or disorder or the symptoms thereof [pg 37 pgh 5 line 1]. The nature of the invention is a therapeutic GIP agonist. However, the prior art does not support the conjecture that diabetes can be cured.
Joslin Education Team. (2020, March 9). Can type 2 diabetes be reversed? Joslin Diabetes Center. https://joslin.org/news-stories/all-news-stories/education/2020/03/can-type-2-diabetes-be-reversed
Joslin states that according to recent research, type 2 diabetes cannot be cured, but individuals can have glucose levels that return to non-diabetes range, (complete remission) or pre-diabetes glucose level (partial remission) by losing significant amounts of weight [pgh 3]. This is remission, not a cure because beta cells have been damaged and the underlying genetic factors contributing to the person’s susceptibility to diabetes remain intact [pgh 4].
Thus, the level of one of ordinary skill in the art allows them to understand that diabetes cannot be cured. Nor, is it predictable that the beta cell damage caused by diabetes can be reversed. The inventors provide direction by describing:
SEQ ID NO: 4-38’s in vitro potency and affinity to GLP-1 and GIP human receptors [pg 88-92]
The pharmokinetic profiles of SEQ ID NO: 6, 16, 19, 21-22, and 35 in mice/rats [pg 92-93]
The pharmokinetic profile of SEQ ID NO: 19 in minipigs [pg 94]; and
The effect on glucose excursion and tolerance of SEQ ID NO: 6 and 35 and increasing dose [pg 94-98].
The contents of the disclosure combined with the existing working examples taught by Joslin do not enable the claimed invention to cure type 2 diabetes. Undue experimentation by studying the cellular behavior after diabetes remission with the invention would be required to support such a conjecture.
Thus claim 12, while enabled for the scope of shortening the duration, ameliorating, slowing down, inhibiting progression or worsening, and prevention of diabetes, is not enabled for curing type 2 diabetes.
Claim 13 is 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 shortening the duration, ameliorating, slowing down, inhibiting progression or worsening, and prevention of obesity, does not reasonably provide enablement for the complete scope of treating obesity. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The breadth of claim 13 encompasses using a compound of formula I to cure obesity. Applicant’s lexicography alters the scope of “treating/treatment of a disease or disorder" to include curing, shortening the duration, ameliorating, slowing down or inhibiting progression or worsening of a disease or disorder or the symptoms thereof [pg 37 pgh 5 line 1]. The nature of the invention is a therapeutic GIP agonist. However, the state of the art does not support the conjecture that obesity can be cured.
(“Obesity is a chronic relapsing condition that cannot be cured with a drug alone” warn public health experts. (2026, March 4). Loughborough University. https://www.lboro.ac.uk/media-centre/press-releases/2026/march/weight-loss-drugs)
Obesity is a chronic relapsing condition that cannot be cured with a drug alone. [Title]. Studies show that as soon as you come off GLP-1, the weight goes back on because people have not learned to manage their weight [pgh 4]. Obesity is a chronic relapsing condition that cannot be cured with a drug alone [pgh 8].
Furthermore, there is a high bar for what can be considered a curable disease:
(What is a Cure? (2023, January 20). Cleveland Clinic. https://my.clevelandclinic.org/health/articles/24434-cure)
“Being cured of a disease means it’s completely gone and isn’t coming back. For many people, cures represent the ultimate treatment goal. Most diseases and conditions aren’t curable” [Abstract]. Cure and recovery are different because you can recover from a disease without being cured of it [The difference between a cure and recovery]. Also, cure and remission are different because while a cure means that a disease has gone for good, remission doesn’t come with that guarantee [The difference between a cure and remission].
Thus, the level of one of ordinary skill in the art allows them to understand that obesity cannot be cured because one must take a GLP-1 agonist for a lifetime in order for the disease to not come back. Nor, is it predictable that every patient with obesity will not gain weight back and be completely cured of obesity after treatment. The inventors provide direction by describing:
SEQ ID NO: 4-38’s in vitro potency and affinity to GLP-1 and GIP human receptors [pg 88-92]
The pharmokinetic profiles of SEQ ID NO: 6, 16, 19, 21-22, and 35 in mice/rats [pg 92-93]
The pharmokinetic profile of SEQ ID NO: 19 in minipigs [pg 94]; and
The effect on glucose excursion and tolerance of SEQ ID NO: 6 and 35 and increasing dose [pg 94-98].
The contents of the disclosure combined with the existing working examples in Loughborough University and Cleveland Clinic do not enable the claimed invention to cure osteoporosis. Undue experimentation by studying patients’ weight after stopping treatment would be required to make such a conjecture.
Thus, the applicant while enabled for the scope of shortening the duration, ameliorating, slowing down, inhibiting progression or worsening, and prevention of obesity, is not enabled for curing obesity.
Claim 14 is 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 shortening the duration, ameliorating, slowing down, inhibiting progression or worsening, and prevention of osteoporosis, does not reasonably provide enablement for the complete scope of treating osteoporosis. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The breadth of claim 14 encompasses using a compound of formula I to cure osteoporosis. Applicant’s lexicography alters the scope of “treating/treatment of a disease or disorder" to include curing, shortening the duration, ameliorating, slowing down or inhibiting progression or worsening of a disease or disorder or the symptoms thereof [pg 37 pgh 5 line 1]. The nature of the invention is a therapeutic GIP agonist. However, the state of the art does not support the conjecture that osteoporosis can be cured.
Orthopedic Specialists of SW Florida. (2022, December 6). Is osteoporosis reversible? Atlantic Health. https://ahs.atlantichealth.org/about-us/stay-connected/news/content-central/2024/is-osteoporosis-reversible.html
The Orthopedic Specialists of SW Florida teach that osteoporosis is a chronic condition caused by a loss in bone density, which means there is no cure but only management of the problem [line 5].
Thus, the level of one of ordinary skill in the art allows them to understand that osteoporosis cannot be cured. Nor, is it predictable that bone density loss can be reversed. The inventors provide direction by describing:
SEQ ID NO: 4-38’s in vitro potency and affinity to GLP-1 and GIP human receptors [pg 88-92]
The pharmokinetic profiles of SEQ ID NO: 6, 16, 19, 21-22, and 35 in mice/rats [pg 92-93]
The pharmokinetic profile of SEQ ID NO: 19 in minipigs [pg 94]; and
The effect on glucose excursion and tolerance of SEQ ID NO: 6 and 35 and increasing dose [pg 94-98].
The contents of the disclosure combined with the existing working examples in SW Florida do not enable the claimed invention to cure osteoporosis. Undue experimentation by studying bone density during treatment would be required to support such a conjecture.
Thus claim 14, while enabled for the scope of shortening the duration, ameliorating, slowing down, inhibiting progression or worsening, and prevention of osteoporosis, are not enabled for curing osteoporosis.
Claim 16 is 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 shortening the duration, ameliorating, slowing down, inhibiting progression or worsening, and prevention of type 2 diabetes and obesity, does not reasonably provide enablement for the complete scope of treating diabetes and obesity. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The breadth of claim 16 encompasses using a compound of formula I to treat type 1 diabetes and cure type 1 and type 2 diabetes and obesity. Applicant’s lexicography alters the scope of “treating/treatment of a disease or disorder" to include curing, shortening the duration, ameliorating, slowing down or inhibiting progression or worsening of a disease or disorder or the symptoms thereof [pg 37 pgh 5 line 1]. The nature of the invention is a therapeutic GIP agonist. However, the prior art does not support the conjecture that type 1 diabetes can be treated and that both type 1 and type 2 diabetes and obesity can be cured.
(Halperin, I. (2025, December 2). Can type 1 diabetes be delayed or prevented? Diabetes Care Community. https://www.diabetescarecommunity.ca/diabetes-overview-articles/type-1-diabetes-definition/can-type-1-diabetes-be-delayed-or-prevented/)
Halperin teaches that genetic factors, family history, and possibly environmental triggers all play a role in the development of type 1 diabetes [How does type 1 diabetes develop?]. There is no way to fully prevent type 1 diabetes because it is an autoimmune condition [Can type 1 diabetes actually be prevented?]. The body’s immune system attacks its own beta cells, and this process usually cannot be stopped once it begins. Immunotherapy trials are underway to delay the onset of T1D.
Thus, the level of one of ordinary skill in the art allows them to understand that diabetes cannot be prevented or cured, and that is not predictable that a GIP agonist can shorten the duration, ameliorate, slow or inhibit progression or worsening of type 1 diabetes because it is not an immunotherapy agent and is not been supported by the disclosure in such a way.
(Joslin Education Team. (2020, March 9). Can type 2 diabetes be reversed? Joslin Diabetes Center.)
Joslin states that according to recent research, type 2 diabetes cannot be cured, but individuals can have glucose levels that return to non-diabetes range, (complete remission) or pre-diabetes glucose level (partial remission) by losing significant amounts of weight [pgh 3]. This is remission, not a cure because beta cells have been damaged and the underlying genetic factors contributing to the person’s susceptibility to diabetes remain intact [pgh 4].
Thus, the level of one of ordinary skill in the art allows them to understand that type 2 diabetes cannot be cured. Nor, is it predictable that the beta cell damage caused by diabetes can be reversed.
(“Obesity is a chronic relapsing condition that cannot be cured with a drug alone” warn public health experts. (2026, March 4). Loughborough University. https://www.lboro.ac.uk/media-centre/press-releases/2026/march/weight-loss-drugs)
(What is a Cure? (2023, January 20). Cleveland Clinic. https://my.clevelandclinic.org/health/articles/24434-cure)
Obesity is a chronic relapsing condition that cannot be cured with a drug alone. [Title]. Studies show that as soon as you come off GLP-1, the weight goes back on because people are not learning to manage their weight [pgh 4]. Obesity is a chronic relapsing condition that cannot be cured with a drug alone [pgh 8].
Furthermore, there is a high bar for what can be considered a curable disease:
“Being cured of a disease means it’s completely gone and isn’t coming back. For many people, cures represent the ultimate treatment goal. Most diseases and conditions aren’t curable” [Abstract]. Cure and recovery are different because you can recover from a disease without being cured of it [The difference between a cure and recovery]. Cure and remission are different because while a cure means that a disease has gone for good, remission doesn’t come with that guarantee [The difference between a cure and remission].
Thus, the level of one of ordinary skill in the art allows them to understand that obesity cannot be cured because one has to take a GLP-1 agonist for a lifetime in order for the disease to not come back. Nor, is it predictable that every patient with obesity will not gain weight back after treatment.
The inventors provide direction by describing:
SEQ ID NO: 4-38’s in vitro potency and affinity to GLP-1 and GIP human receptors [pg 88-92]
The pharmokinetic profiles of SEQ ID NO: 6, 16, 19, 21-22, and 35 in mice/rats [pg 92-93]
The pharmokinetic profile of SEQ ID NO: 19 in minipigs [pg 94]; and
The effect on glucose excursion and tolerance of SEQ ID NO: 6 and 35 and increasing dose [pg 94-98].
The contents of the disclosure combined with the existing working examples taught by Halperin, Joslin, and Loughborough do not enable the claimed invention to treat type 1 diabetes and cure type 2 diabetes and obesity. Undue experimentation by studying cellular behavior after diabetes remission and weight changes after treatment with the invention would be required to support such a conjecture.
Thus claim 16, while enabled for the scope of shortening the duration, ameliorating, slowing down, inhibiting progression or worsening, and prevention of diabetes, is not enabled for curing type 2 diabetes and obesity.
Claims 10-19 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. While the applicant does have support the SEQ ID NO: 4-38 reduced in practice, they do not have support the genus of peptides represented by SEQ ID NO: 39.
Claim 1 recites “A compound of formula I.” However, the specification does not support that the inventors possess the complete recited genus and that the complete genus is able to treat glucose intolerance and insulin resistance -related diseases.
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, reduction to drawings, 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 [MPEP 2163 ii)].
The inventors provide direction by demonstrating the:
Synthesis of SEQ ID NO: 6, 19, 25, 28, and 36 [pg 77-81]
Comparison of calculated vs found molecular weight SEQ ID NO: 4-38 [pg 81 Table 2]
Stability and solubility of SEQ ID NO: 4-38 in buffer systems [pg 82-86]
Stability of SEQ ID: 4-38 in buffer system A assessed in ThT assay [pg 86-87]
SEQ ID NO: 4-38 in vitro potency and affinity to GLP-1 and GIP human receptors [pg 88-92]
Pharmokinetic profiles of SEQ ID NO: 6, 16, 19, 21-22, and 35 in mice/rats [pg 92-93]
Pharmokinetic profile of SEQ ID NO: 19 in minipigs [pg 94]; and
Effect on glucose excursion and tolerance of SEQ ID NO: 6 and 35 and increasing dose [pg 94-98].
Overall, applicant demonstrates adequate written description support for SEQ ID NO: 4-38. However, the SEQ ID NO:4-38 reduced to practice by the applicant are not representative of the entire genus of compounds of formula I claimed. Nor, would one of ordinary skill in the art be able to attest to the complete genus’s ability to treat glucose intolerance and insulin resistance-related diseases. There is a high level of unpredictability and complexity associated with performing substitutions and adding various functional groups that affect the functional abilities of a compound. Furthermore, the applicant does not disclose relevant, functional characteristics or motifs necessary, or unnecessary for the formula to act as a GIP receptor agonist. Thus, while the applicant has support for the specific sequences reduced to practice, they do not have support for the complete genus of variants of SEQ ID NO: 39.
Claims 11-19 do not narrow the genus of compounds of formula I and therefore do not fulfill the written description requirement because based on the disclosure, one of ordinary skill in the art cannot attest to the applicant’s possession of a representative number of species capable of the functional capabilities claimed.
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 10 and 12-18 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.
Claims 12-18 recite the limitation "for use according to claim 1" in the preamble. There is insufficient antecedent basis for this limitation in the claim because there is no use claim 1’s limitations.
Claim 10 recited “for use in human medicine.” This is a further limitation but does not necessarily change the scope of base claim 1. The recitation of the intended use of the claimed invention does not result in a structural difference between the compound of claim 1 and claim 10 because it is unclear what the scope of “use in human medicine.” Thus, claim 10 is indefinite.
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 and 10-19 are rejected under 35 U.S.C. 103 as being unpatentable over Asami et al. (US20180298070A1) in view of Haack et al. (WO2014096145A1).
Asami et al. presents a peptide compound having an activating action on GIP receptors and use of the peptide compound as a medicament [0001]. Claim 1 maps to instant SEQ ID NO: 19 as the following:
Claim 1
Asami et al.
R1 is H or C1-C4 alkyl
P1 represented by RA1 wherein RA1 is H or a hydrocarbon
NH
N-terminus
1
Tyr
Tyr
2
Aib
Aib or D-Ala
3
Glu
Glu
4
Gly
Gly
5
Thr
Thr
6
Phe, Iva, Abu, or Mva
Iva, Phe, or Val
7
Ile
Ile, Lys, or Val
8
Ser
Ser
9
Asp
Asp, Leu, or Phe
10
Leu or Hol
Tyr
Difference Tyr10 -> Leu or Hol
11
Ser
Aib or Ser
12
Ile
Ile
13
Aib
Aib, Ala, Gln, Leu, Tyr, or D-Iva
14
Leu or Lys wherein the -NH2 side chain group is functionalized
Leu
15
Glu or Asp
Asp, Glu, Lys, Ser, or Tyr
16
Glu or Arg
Arg or Lys
17
Ile, Gln or Aib
Aib, Gln, Ile
18
His or Lys wherein the -NH2 side chain group is functionalized
Ala or His
19
Gln
Gln or Ser
20
Glu or Aib
Aib, Ala, or Gln
21
Glu
Asn, Asp, Glu, Leu, or Ser
22
Phe or Mph
Phe or Mph
23
Ile
IIe or Val
24
Glu or Gln
Arg, Asn, Asp, Lys, or Lys(Ac)
Difference Asn24 -> Glu or Gln
25
Trp
Trp
26
Leu or Iva
Aib, Iva, or Leu
27
Leu or Tba
Leu
28
Ala
Ala, Arg, Lys, or Lys(Ac)
29
Gln
Gln or Gly
30
Gly, Arg, Glu, or Lys
Arg or Gly, or deletion
31
Gly, Pro-Ser-Ser-Gly-Ala- Pro-Pro- Pro-Ser (SEQ ID NO: 40), Pro-Ser-Ser-Gly-Glu-Pro-Pro-Pro-Ser (SEQ ID NO: 41) or when X30 is Lys then X31 is Pro-Ser-Ser-Aib-Lys-Ala-Pro-Pro-Pro-Lys (SEQ ID NO: 42)
Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-deletion (A31-A40)
R2
NH2 or OH
P2 represents —NH2 or —OH
wherein any one or two amino acids selected from A8 to A30 optionally represent Lys(R), and R represents a substituent group [claim 1]. Asami et al. does not teach that the GIP-R agonist comprises Leu or Hol at position 10 and Glu or Gln at position 24.
Haack et al. presents exendin-4 peptide analogues which activate the glucagon-like peptide 1 (GLP-1 ) and the glucose-dependent insulinotropic polypeptide (GIP) receptor. Haack et al. states that:
Compounds of this invention are exendin-4 peptide analogues comprising leucine in position 10 and glutamine in position 13…. In particular, residues Tyr10 and Tyr13, are replaced by leucine in position 10 and glutamine, a non-aromatic polar amino acid, in position 13. This replacement, especially in combination with isoleucine in position 23 and glutamate in position 24 leads to exendin-4 derivatives with potentially improved biophysical properties as solubility or aggregation behavior in solution. The non-conservative replacement of an aromatic amino acid with a polar amino acid in position 13 of an exendin-4 analogue surprisingly leads to peptides with high activity on the GIP receptor and optionally on the glucagon receptor. Furthermore, compounds of this invention are exendin-4 derivatives with fatty acid acylated residues in position 14. This fatty acid functionalization in position 14 results in an improved pharmacokinetic profile. Surprisingly, the fatty acid functionalization in position 14 also leads to peptides with a significantly higher GIPR activity [pg 5 line 27-pg 6 line 13].
Thus, Haack et al., motivates one of ordinary skill in the art to perform the non-conservative Y10L substitution in combination with a glutamate substitution at position 24 on Asami’s formula to arrive to peptide encompassed by instant SEQ ID NO: 39. Therefore, prior to the effective filing date, it was obvious to combine Asami and Haack et al.’s teachings to obtain a peptide with higher activity on the GIP receptor.
Regarding claim 10, Asami’s invention relates to a peptide compound having an activating action on GIP receptors and use of the peptide compound as a medicament and Asami teaches the parts by weight of the peptide when the subject of administration is human [0001 and 1083].
Regarding claim 11, Asami specifies that a medicament containing the compound of the present invention is obtained using the compound of the present invention alone or in admixture with a pharmacologically acceptable carrier [1023].
Regarding claim 12, Asami states that the compound of the present invention is used as an agent for the prophylaxis or treatment of diabetes determined according to the above-mentioned new diagnostic criteria, borderline type diabetes, impaired glucose tolerance, IFG (Impaired Fasting Glucose) and IFG (Impaired Fasting Glycemia) [1012].
Regarding claim 13, Asami states that the invention can be used for the prophylaxis or treatment of, for example, symptomatic obesity, obesity based on simple obesity, disease state or disease associated with obesity [1004].
Regarding claim 14, Asami states that the present invention can be used as an agent for the prophylaxis or treatment of osteopenia, a disease encompassed by the need for treatment for the prevention of osteoporosis [1004].
Regarding claim 15, Asami states that the compound of the present invention may be used as a preventive/therapeutic agent for vomiting or nausea [1015].
Regarding claim 16, Asami states that the compound can be sued as an agent for the treatment or prophylaxis of various diseases including diabetes and obesity [1004].
Regarding claim 17, Asami et al. show that the compounds of their invention suppress increases in blood glucose levels caused by oral glucose loading [1277].
Regarding claim 18, Asami et al. state that the compound of the present invention is also useful as a feeding suppressant and a weight reducing agent [1022].
Regarding claim 19, Asami teaches that their invention may be administered as a pharmaceutical preparation [1023].
Claims 2-3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Asami et al. (US20180298070A1) in view of Haack et al. (WO2014096145A1), as applied to claims 1 and 10-19, and in further view of Abraham et al. (WO2020023386A1).
Asami et al. and Haack et al. map to instant SEQ ID NO: 44 as the following:
Claim 2
Asami et al.
Haack et al.
R1 is H or C1-C4 alkyl
P1 represented by RA1 wherein RA1 is H or a hydrocarbon
NH
N-terminus
1
Tyr
Tyr
2
Aib
Aib or D-Ala
3
Glu
Glu
4
Gly
Gly
5
Thr
Thr
6
Phe or Iva
Iva, Phe, or Val
7
Ile
Ile, Lys, or Val
8
Ser
Ser
9
Asp
Asp, Leu, or Phe
10
Leu
Tyr
Teaches Tyr10 -> Leu
11
Ser
Aib or Ser
12
Ile
Ile
13
Aib
Aib, Ala, Gln, Leu, Tyr, or D-Iva
14
Lys wherein the -NH2 side chain group is functionalized
Lys(R) [0651 and 0919]
R is X-L-, wherein L is a 5-6 glycine linker and X is a C16-C20 linear saturated dicarboxylic acid [0650]
Does not teach
{AEEA} 2-gGlu-C 180H, {AEEA} 2-gGlu-C200H, {AEEA}3-gGlu-C180H, {AEEA}2- {gGlu} 2-C180H, {AEEA} 2- {gGlu} 2-C200H, {Gly}3-gGlu-C180H or {N-MeGly}3-gGlu-C180H
15
Asp
Asp, Glu, Lys, Ser, or Tyr
16
Arg
Arg or Lys
17
Ile
Aib, Gln, Ile
18
His
Ala or His
19
Gln
Gln or Ser
20
Glu or Aib
Aib, Ala, or Gln
21
Glu
Asn, Asp, Glu, Leu, or Ser
22
Phe or Mph
Phe or Mph
23
Ile
IIe or Val
24
Glu
Arg, Asn, Asp, Lys, or Lys(Ac)
Difference Asn24 -> Glu
25
Trp
Trp
26
Leu
Aib, Iva, or Leu
27
Leu
Leu
28
Ala
Ala, Arg, Lys, or Lys(Ac)
29
Gln
Gln or Gly
30
Glu or Arg
Arg or Gly, or deletion
31
Gly
Deletion-deletion-deletion-Gly-deletion-deletion-deletion-deletion-deletion-deletion [A31-A40]
R2
NH2 or OH
P2 represents —NH2 or —OH
Asami et al. teach that its peptide may be a modified lysine at position 14 with a fatty acid comprising a glycine linker and dicarboxylic acid [0650-0651 and 0919]. Haack et al. teach that fatty acid functionalization in position 14 results in an improved pharmacokinetic profile and significantly higher GIPR activity [pg 5 line 27-pg 6 line 13]. Asami et al. and Haack et al. do not teach the specific claimed functional groups on the lysine of X14.
Abraham et al. presents an invention relating to compounds having an extended duration of action at glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1), wherein position 14 is a lysine modified with a C16-22 fatty acid via an optional linker [pg 1 line 4 and pg 3 line 3]. Abraham et al. teach that:
Xl4 or Xl7 is selected from the group consisting of K(2-[2-(2-Amino- ethoxy)-ethoxy]-acetyl)2-( -Glu)-C0-(CH2)i6-C02H, K(2-[2-(2-Amino-ethoxy)-ethoxy]- acetyl)2-(Y-Glu)-C0-(CH2)i8-C02H, K(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(Y-Glu)-CO- (CH2)i4-C02H, K(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-C0-(CH2)i8-C02H, K(2-[2-(2-Amino-ethoxy)-ethoxy] -acetyl )-( /-Glu)-(Trx)-CO-(CH2)i8-CO2H, K(2-[2-(2-Amino-ethoxy)- ethoxy]-acetyl)-(Trx)-( ;/-Glu)-C0-(CH2)i8-C02H, K(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)- (SK)-(Y-G1U)-C0-(CH2)I 8-C02H, K(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(sK)-(sK)-CO- (CH2)i8-C02H, K(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(Y-Glu)2-C0-(CH2)i8-C02H, K(2- [2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-C0-(CH2)i8-C02H, K(2-[2-(2-Amino-ethoxy)- ethoxy]-acetyl)2-(sK)-C0-(CH2)i6-C02H, K(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(sK)- C0-(CH2)i4-C02H, and KDab-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Dab-(2-[2-(2- Amino-ethoxy)-ethoxy]-acetyl)-C0-(CH2)i8-C02H [pg 6 line 1–pg 7 line 5].
Therefore, prior to the effective filing date, one of ordinary skill in the art would find it obvious to take the peptide taught by Asami and Haack et al. and replace the position 14 functionalization with the one taught by Abraham et al. to obtain a peptide with improved duration of action, activity, and pharmokinetics.
Regarding claim 3, Asami et al. and Haack et al. map to instant SEQ ID NO: 45 as the following:
Claim 3
Asami et al.
Haack et al.
R1 is H or C1-C4 alkyl
P1 represented by RA1 wherein RA1 is H or a hydrocarbon
NH
N-terminus
1
Tyr
Tyr
2
Aib
Aib or D-Ala
3
Glu
Glu
4
Gly
Gly
5
Thr
Thr
6
Phe, Iva, Abu, or Mva
Iva, Phe, or Val
7
Ile
Ile, Lys, or Val
8
Ser
Ser
9
Asp
Asp, Leu, or Phe
10
Leu or Hol
Tyr
Difference Tyr10 -> Leu
11
Ser
Aib or Ser
12
Ile
Ile
13
Aib
Aib, Ala, Gln, Leu, Tyr, or D-Iva
14
Lys functionalized by {AEEA} 2-gGlu-C18OH
Lys(R) [0651 and 0919]
R is X-L-, wherein L is a 5-6 glycine linker and X is a C16-C20 linear saturated dicarboxylic acid [0650]
Does not teach {AEEA} 2-gGlu-C18OH
15
Glu or Asp
Asp, Glu, Lys, Ser, or Tyr
16
Glu or Arg
Arg or Lys
17
Ile, Gln or Aib
Aib, Gln, Ile
18
His
Ala or His
19
Gln
Gln or Ser
20
Glu or Aib
Aib, Ala, or Gln
21
Glu
Asn, Asp, Glu, Leu, or Ser
22
Phe or Mph
Phe or Mph
23
Ile
IIe or Val
24
Glu or Gln
Arg, Asn, Asp, Lys, or Lys(Ac)
Difference Asn24 -> Glu or Gln
25
Trp
Trp
26
Leu or Iva
Aib, Iva, or Leu
27
Leu or Tba
Leu
28
Ala
Ala, Arg, Lys, or Lys(Ac)
29
Gln
Gln or Gly
30
Gly, Arg. Glu or Lys
Arg or Gly, or deletion
31
Gly, Pro-Ser-Ser-Gly-Ala- Pro-Pro- Pro-Ser (SEQ ID NO: 40), Pro-Ser-Ser-Gly-Glu-Pro-Pro-Pro-Ser (SEQ ID NO: 41) or when X30 is Lys then X31 is Pro-Ser-Ser-Aib-Lys-Ala-Pro-Pro-Pro-Lys (SEQ ID NO: 42)
Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-deletion (A31-A40)
R2
NH2 or OH
P2 represents —NH2 or —OH
Asami et al. teach that its peptide may be a modified lysine at position 14 with a fatty acid comprising a glycine linker and dicarboxylic acid [0650-0651 and 0919]. Haack et al. teach that fatty acid functionalization in position 14 results in an improved pharmacokinetic profile and significantly higher GIPR activity [pg 5 line 27-pg 6 line 13]. Asami et al. and Haack et al. do not teach the specific claimed functional groups on the lysine of X14.
Abraham et al. presents an invention relating to compounds having an extended duration of action at glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1), wherein position 14 is a lysine modified with a C16-22 fatty acid via an optional linker [pg 1 line 4 and pg 3 line 3]. Abraham et al. teach Xl4 or Xl7 is selected from the group including {AEEA} 2-gGlu-C18OH [pg 6 line 1–pg 7 line 5]. Specifically, Abraham et al’s compound 27 has K{AEEA} 2-gGlu-C200H at position 14 and still has activity against GIP-R [pg 41 and 98].
Therefore, prior to the effective filing date, one of ordinary skill in the art would find it obvious to take the peptide taught by Asami and Haack et al. and replace the position 14 functionalization with the one taught by Abraham et al. to obtain a peptide with improved duration of action, activity, and pharmokinetics.
Regarding claim 5, Asami et al. and Haack et al. map to instant SEQ ID NO: 47 as the following:
Claim 5
Asami et al.
Haack et al.
R1 is H or C1-C4 alkyl
P1 represented by RA1 wherein RA1 is H or a hydrocarbon
NH
N-terminus
1
Tyr
Tyr
2
Aib
Aib or D-Ala
3
Glu
Glu
4
Gly
Gly
5
Thr
Thr
6
Phe, Iva, Abu, or Mva
Iva, Phe, or Val
7
Ile
Ile, Lys, or Val
8
Ser
Ser
9
Asp
Asp, Leu, or Phe
10
Leu or Hol
Tyr
Difference Tyr10 -> Leu
11
Ser
Aib or Ser
12
Ile
Ile
13
Aib
Aib, Ala, Gln, Leu, Tyr, or D-Iva
14
Lys functionalized by {AEEA} 2-gGlu-C18OH
Lys(R) [0651 and 0919]
R is X-L-, wherein L is a 5-6 glycine linker and X is a C16-C20 linear saturated dicarboxylic acid [0650]
Does not teach {AEEA} 2-gGlu-C18OH
15
Glu or Asp
Asp, Glu, Lys, Ser, or Tyr
16
Glu or Arg
Arg or Lys
17
Ile or Aib
Aib, Gln, Ile
18
His
Ala or His
19
Gln
Gln or Ser
20
Glu or Aib
Aib, Ala, or Gln
21
Glu
Asn, Asp, Glu, Leu, or Ser
22
Phe or Mph
Phe or Mph
23
Ile
IIe or Val
24
Glu or Gln
Arg, Asn, Asp, Lys, or Lys(Ac)
Difference Asn24 -> Glu or Gln
25
Trp
Trp
26
Leu or Iva
Aib, Iva, or Leu
27
Leu or Tba
Leu
28
Ala
Ala, Arg, Lys, or Lys(Ac)
29
Gln
Gln or Gly
30
Gly, Arg or Glu
Arg or Gly, or deletion
31
Gly, Pro-Ser-Ser-Gly-Ala- Pro-Pro- Pro-Ser (SEQ ID NO: 40)
Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-deletion (A31-A40)
R2
NH2 or OH
P2 represents —NH2 or —OH
Asami et al. teach that its peptide may be a modified lysine at position 14 with a fatty acid comprising a glycine linker and dicarboxylic acid [0650-0651 and 0919]. Haack et al. teach that fatty acid functionalization in position 14 results in an improved pharmacokinetic profile and significantly higher GIPR activity [pg 5 line 27-pg 6 line 13]. Asami et al. and Haack et al. do not teach the specific claimed functional groups on the lysine of X14.
Abraham et al. presents an invention relating to compounds having an extended duration of action at glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1), wherein position 14 is a lysine modified with a C16-22 fatty acid via an optional linker [pg 1 line 4 and pg 3 line 3]. Abraham et al. teach Xl4 or Xl7 is selected from the group including {AEEA} 2-gGlu-C18OH [pg 6 line 1–pg 7 line 5]. Specifically, Abraham et al’s compound 27 has K{AEEA} 2-gGlu-C200H at position 14 and still has activity against GIP-R [pg 41 and 98].
Therefore, prior to the effective filing date, one of ordinary skill in the art would find it obvious to take the peptide taught by Asami and Haack et al. and replace the position 14 functionalization with the one taught by Abraham et al. to obtain a peptide with improved duration of action, activity, and pharmokinetics.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Asami et al. (US20180298070A1) in view of Haack et al. (WO2014096145A1), as applied to claims 1 and 10-19, and in further view of Rosenkilde et al. (US20200087373A1) and Abraham et al. (WO2020023386A1).
Asami et al. and Haack et al. map to instant SEQ ID NO: 44 as the following:
Claim 4
Asami et al.
Haack et al.
R1 is H or C1-C4 alkyl
P1 represented by RA1 wherein RA1 is H or a hydrocarbon
NH
N-terminus
1
Tyr
Tyr
2
Aib
Aib or D-Ala
3
Glu
Glu
4
Gly
Gly
5
Thr
Thr
6
Phe
Iva, Phe, or Val
7
Ile
Ile, Lys, or Val
8
Ser
Ser
9
Asp
Asp, Leu, or Phe
10
Leu
Tyr
Teaches Tyr10 -> Leu
11
Ser
Aib or Ser
12
Ile
Ile
13
Aib
Aib, Ala, Gln, Leu, Tyr, or D-Iva
14
Leu
Leu
15
Asp or Glu
Asp, Glu, Lys, Ser, or Tyr
16
Glu or Arg
Arg or Lys
17
Gln or Ile
Aib, Gln, Ile
18
Lys functionalized by {AEEA} 2-gGlu-C 180H
Ala or His
Does not teach Lys functionalized by
{AEEA} 2-gGlu-C 180H
19
Gln
Gln or Ser
20
Aib
Aib, Ala, or Gln
21
Glu
Asn, Asp, Glu, Leu, or Ser
22
Phe
Phe or Mph
23
Ile
IIe or Val
24
Glu
Arg, Asn, Asp, Lys, or Lys(Ac)
Difference Asn24 -> Glu
25
Trp
Trp
26
Leu
Aib, Iva, or Leu
27
Leu
Leu
28
Ala
Ala, Arg, Lys, or Lys(Ac)
29
Gln
Gln or Gly
30
Gly
Arg or Gly, or deletion
31
Gly, Pro-Ser-Ser-Gly-Ala- Pro-Pro- Pro-Ser (SEQ ID NO: 40)
Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-deletion (A31-A40)
R2
NH2 or OH
P2 represents —NH2 or —OH
Asami et al. and Haack et al. do not teach the lysine of X18 with the specific claimed functional groups.
Rosenkilde et al. disclose antagonists of the GIP receptor comprising at least one fatty acid molecule to increase half-life while maintaining antagonistic properties [Abstract]. Rosekilde et al. claim GLP-derived peptide analogues with lysine at position 18 [SEQ ID NO: 72, 75, and 126-128] wherein the peptides comprises at least one fatty acid molecule at one or more amino acid residues at position 2 to 19, wherein said fatty acid molecule is attached to an amino acid residue via a spacer, wherein said spacer optionally comprises one or more moieties individually selected from the group consisting of: one or more α,ω-amino acids; one or more amino acids selected from the group consisting of: succinic acid, Lys, Glu, and Asp; 4-Abu; y-aminobuturic acid; a dipeptide; one or more of: γ-aminobutanoyl (γ-aminobutyric acid), γ-glutamyl (γ-glutamic acid), β-asparagyl, β-alanyl and glycyl; and [γ-glutamic acid-8-amino-3,6-dioxaoctanoic acid]n (γGlu-AEEAcn), wherein n is an integer between 1 and 50 [claims 16-17]. Specifically, Rosenkilde demonstrates that the analogue may have the K18+y-glutamic acid+ one or more repeats of 8-amino-3,6-dioxaoctanoic acid modification. [0353]. Thus, Rosenkilde et al. make obvious a H18K substitution modified with a fatty acid containing y-Glu and an AEEA chain. Rosenkilde et al. does not teach the specific {AEEA} 2-gGlu-C 180H functionalization.
Abraham et al. present an invention relating to compounds having an extended duration of action [pg 1 line 4]. Abraham et al. teach that the modification done at position 14 or 17 lysine is selected from the group including {AEEA} 2-gGlu-C18OH [pg 6 line 1–pg 7 line 5]. Specifically, Abraham et al’s compound 27 has K{AEEA} 2-gGlu-C200H at position 14 and still has activity against GIP-R [pg 41 and 98]. One of ordinary skill in the art would recognize the functionalization taught by Abraham et al. to be a viable substitution for the fatty acid functionalization of K18 taught by Rosenkilde.
Therefore, prior to the effective filing date, it was obvious to substitute position 18 with lysine taught by Rosenkilde in the peptide taught by Asami and Haack et al. and functionalize the substituted peptide as taught by Abraham to obtain a peptide with improved duration of action and half-life.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: SEQ ID NO: 4-38 are nonobvious over Asami et al. (US20180298070A1) in view of Haack et al. (WO2014096145A1), as applied to claims 1 and 10-19, in further view of Rosenkilde et al. (US20200087373A1) and Abraham et al. (WO2020023386A1).
Asami et al. teaches the genus of formula I, apart from position 10 and 24, taught by Haack et al. However, a genus does not always anticipate a claim to a species [MPEP 2131.02 and Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990)].
A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) [MPEP 2131.02].
For a person of ordinary skill in the art to at once envisage instant SEQ ID NO: 4-38, the specific sequences would have to be taught by Asami et al., with their missing limitations of position 10, 18 and 24 found in secondary references Haack, Rosenkilde, or Abraham et al. However, none of the specific sequences disclosed by Asami et al. [0927] would render the instant sequences obvious in view of Haack, Rosenkilde, and Abraham et al. Nor, are the substitutions performed by the applicant all well known in the art. For example, with positions 10, 18, and 24 taught by the secondary references, the specific amino acids taught by Asami et al. at positions 17, 21, 23, and 26 in its species could not be used to arrive at SEQ ID NO: 4-38 [0927 and SEQ ID NO: 458-565]. It would take one of ordinary skill in the art hindsight reasoning or serious experimentation to arrive at the instant combinations using the prior art. Thus, claims 6-9 have novel, patentable subject matter.
Claims 6-9 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claim 19 is objected to. Claims 10-19 are rejected under 35 U.S.C. 112(a). Claims 10 and 12-18 rejected under 35 U.S.C. 112(b). Claims 1-5 and 10-19 are rejected under 35 U.S.C. 103. Claims 6-9 are objected to as being dependent upon a rejected base claim.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SACHI JAUHARI whose telephone number is (571)272-3769. The examiner can normally be reached Mon-Fri 9-4.
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/SACHI JAUHARI/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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