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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant's arguments filed 12/29/2025 regarding the rejections under 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicants position is that it is not obvious to derive the instant peptide of General Formula1/SEQ ID NO: 45 and species SEQ ID NO: 37 from the teachings of the references set forth in the prior Office Action because 1) none of the references disclose the functional features set forth in the instant application (Remarks, Pg 16, first paragraph after claim -17, third paragraph) and 2) they do not teach co-administration of a substance as recited in the newly amended claims (Pg 17, 4th paragraph).
Regarding 1), the peptide taught by Jung has an amino acid sequence that is virtually identical to the instant SEQ ID NO: 37, with the exception that position 17 is a Lys rather than an Arg; Unson teaches it is beneficial to have Arg at position 17. Therefore, it is obvious to substitute Lys17 for Arg, leading to the instant SEQ ID NO: 37. One skilled in the art would recognize that amino acid structure is the basis for peptide function; therefore, by disclosing the structure of the instant SEQ ID NO: 37 based upon the teachings of Jung and Unson, one skilled in the art would expect it to have the functional properties described in the instant application. In essence, it is obvious to generate the peptide equivalent to SEQ ID NO: 37; therefore, the claims are obvious.
Regarding 2), the amended claims are still obvious, see art rejections below.
Additionally, Applicant’s request that the double patenting rejections be held in abeyance until at least one allowable claim is identified is noted but the rejections are maintained/modified herein.
Claim Status
Claims 100, 125-137 and 139-140 are pending under examination. Claim 125 was previously withdrawn as a non-elected species. Claims 100, 126, 136, 139, and 140 are currently amended. Claims 1-99, 101-124, and 138 were previously cancelled.
Priority
The instant application is the 371 national stage entry of PCT/KR2019/013057, filed 10/4/2019, which claims priority to KR10-2018-0118463, filed 10/4/2018, and KR10-2018-0118462, also filed 10/4/2018. Applicants have claimed the effective date of 10/4/2018 based on KR10-2018-0118463 and KR10-2018-0118462 although no translation has been made of record.
Claim Interpretation
Claims 128 and 129 recite a method for treating metabolic syndrome comprising administering to a subject in need thereof a pharmaceutical composition comprising a substance with activity to a glucagon receptor or a conjugate thereof… wherein the substance with activity to a glucagon receptor is a peptide, wherein the peptide comprises an amino acid sequence selected from the group consisting of...” (emphasis added). This claim is being interpreted to mean that a peptide or protein encompassing or containing the entirety of one of the SEQ ID NO’s listed meets the limitation of the claim. Conversely, smaller fragments encompassed by the SEQ ID NO’s listed are being interpreted as not meeting the limitations of the claim.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
First rejection
Claim(s) 100, 126-137, and 139-140 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 2018/0186853 A1, filed 6/29/2016, published 7/5/2018) in view of Rauch et al. (WO2013167554A1, published 11/14/2013).
Kim teaches pharmaceutical compositions and methods for treating metabolic syndrome by administering to a subject in need thereof a pharmaceutical composition containing a glucagon derivative and at least one compound or material having a therapeutic activity for metabolic syndrome ([0015, 0021, 0023]).
The glucagon derivative is a peptide of General Formula 1 (SEQ ID NO, 45):
X1-X2-QGTF-X7-SD-X10-S-X12-X13-X14-X15-X16-X17-X18-Xl9-X20-X21-F-X23-X24-W-L-X27-X28-X29-X30, wherein X1 is histidine, desamino-histidyl, N-dimethylhistidyl, β-hydroxy imidazopropionyl, 4-imidazoacetyl, β-carboxy imidazopropionyl, tryptophan, or tyrosine, or is
absent; X2 is a-methyl-glutamic acid, aminoisobutyric acid (Aib), D-alanine, glycine, Sar(N-methylglycine), serine, or D-serine; X7 is threonine, valine, or cysteine; X10 is tyrosine or cysteine; X12 is lysine or cysteine; X13 is tyrosine or cysteine; X14 is leucine or cysteine; X15 is aspartic acid, glutamic acid, or cysteine; X16 is glutamic acid, aspartic acid, serine, α-methyl-glutamic acid, or cysteine, or is absent; X17 is aspartic acid, glutamine, glutamic acid, lysine, arginine, serine, cysteine, or valine, or is absent; X18 is alanine, aspartic acid, glutamic acid, arginine, valine, or cysteine, or is absent; X19 is alanine, arginine, serine, valine, or cysteine, or is absent; X20 is lysine, histidine, glutamine, aspartic acid, lysine, arginine, a-methyl-glutamic acid, or cysteine, or is absent; X21 is aspartic acid, glutamic acid, leucine, valine, or cysteine, or is absent; X23 is isoleucine, valine, or arginine, or is absent; X24 is valine, arginine, alanine, cysteine, glutamic acid, lysine, glutamine, α-methyl-glutamic acid, or leucine, or is absent; X27 is isoleucine, valine, alanine, lysine, methionine, glutamine, or arginine, or is absent; X28 is glutamine, lysine, asparagine, or arginine, or is absent; X29 is lysine, alanine, glycine, or threonine, or is absent; and X30 is cysteine, or is absent; with the proviso that when the amino acid sequence of General Formula 1 is identical to SEQ ID NO: 1, it is excluded ([0024-0046]). General Formula 1/SEQ ID NO: 45 of the instant claim 1 meets the limitations of General Formula 1/SEQ ID NO: 45 of Kim.
Kim does not teach that the compound or material having a therapeutic activity for metabolic syndrome can be selected from a G protein-coupled agonist, biguanides, sulfonylureas, meglitinide, thiazolidinedione (TZD), a sodium-glucose cotransporter (SGLT2) inhibitor, or an α-glucosidase inhibitor.
Rauch teaches pharmaceutical combinations comprising therapeutic agents to treat metabolic syndrome and associated complications (Pg 4, lines 11-14; Pg 5, lines 11-20). Preferably, at least one therapeutic agent is selected from GPR1 agonists (G protein-coupled agonists), biguanides, sulfonylureas, metiglinides, thiazolidinediones, α-glucosidase inhibitors, and/or SGLT 2 inhibitors (Pg 18, line 33 – Pg 20, line 21; Pg 21, lines 4-17; Pg 23, line 4). Rauch teaches that the combination of therapeutics can improve glycemic control, act synergistically to improve metabolic syndrome and diabetes, allow for dosage reductions that can reduce undesirable side effects, improve fluid retention, and reduce weight gain, (Pg 19, lines 22-27 and 31-36; Pg 20, lines 2-7, lines 10-14, and lines 17-21; and Pg 21, lines 15-17).
Therefore, regarding claim 100, Kim teaches a method of treating metabolic syndrome comprising coadministering a glucagon derivative such as the instant SEQ ID NO: 45 of claim 1 and at least one compound or material having a therapeutic activity for metabolic syndrome. Rauch teaches administering a pharmaceutical composition comprising a combination of therapeutics, wherein at least one is selected from GPR1 agonists (G protein-coupled agonists), biguanides, sulfonylureas, metiglinides, thiazolidinediones, α-glucosidase inhibitors, and/or SGLT 2 inhibitors. Based on these teachings, it would be prima facie obvious to incorporate the therapeutics taught by Rauch into the method taught by Kim. One skilled in the art would be motivated to do so as Rauch established that it was advantageous to combine multiple therapeutics into one pharmaceutical composition for the reasons set forth above. One would have a reasonable expectation of success as Kim had already established a method of successfully treating metabolic syndrome comprising administering a peptide of General Formula 1/SEQ ID NO: 45 in combination with other therapeutics known to treat metabolic syndrome.
Moreover, it would be prima facie obvious to substitute one therapeutic that can treat metabolic syndrome for another. Kim established that the combination of therapeutics comprising a peptide of General Formula 1/SEQ ID NO: 45 and another therapeutic for metabolic syndrome could successfully treat metabolic syndrome. Rauch established additional classes of compounds that can also treat metabolic syndrome. Therefore, the substitution of one therapeutic for another, both of which are known to treat metabolic disorder, is obvious. See MPEP 2143(I)(B).
Additionally, combining equivalents known for the same purpose is prima facie obvious. Per MPEP 2144.06(I), "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). By extension of this logic, it would be obvious to coadminister two therapeutics known to treat metabolic syndrome at the same time, such as the peptide of General Formula 1/SEQ ID NO: 45 taught by Kim and any of those taught by Rauch.
Regarding claim 126, Kim also teaches General Formula 2/SEQ ID NO: 46: Y-Aib-QGTF-X7-SD-X10-S-X12-Y-L-X15-X16-X17-R-A-X20-X21-F-V-X24-W-L-M-N-T-X30, wherein X7 is threonine, valine, or cysteine; X10 is tyrosine or cysteine; X12 is lysine or cysteine; X15 is aspartic acid or cysteine; X16 is glutamic acid or serine; X17 is lysine or arginine; X20 is glutamine or lysine; X21 is aspartic acid or glutamic acid; X24 is valine or glutamine; and X30 is cysteine or is absent, wherein, among the peptides including the amino acid sequence of General Formula 2, the peptides corresponding to SEQ ID NOS: 14, 19, 20, 25, 27, 31, and 33 may be excluded ([0110-0122]). General Formula 2/SEQ ID NO: 46 of the instant claim 126 meets the limitations of General Formula 2/SEQ ID NO: 46 of Kim.
Regarding claim 127, Kim further teaches that the peptide including the amino acid sequence of General Formula 1/SEQ ID NO: 45 is characterized in that it has a pI value different to that of native glucagon, e.g. a pI of less than 6.5 ([0123]), and, in certain embodiments, the peptide of General Formula 1/SEQ ID NO: 45 has at least one amino acid pair among the pairs of X10 and X14, X12 and X16, X16 and X20, X17 and X21, X20 and X24, and X24 and X28 in General Formula 1 is substituted with glutamic acid or lysine, which is capable of forming a ring ([0124-0125]). Similarly, in another embodiment, the aforementioned amino acid pairs forms a ring e.g., a lactam ring ([0126]).
Regarding claims 128 and 129, one glucagon derivative taught by Kim is SEQ ID NO: 37, which is identical to the instant and elected SEQ ID NO: 37 (Sequence Listing, Pg 31), the C-terminus of which is not modified. Kim also teaches embodiments wherein the C-terminus of the peptide is amidated ([0127]), and embodiments wherein the peptide is a glucagon derivative capable of activating a glucagon receptor ([0128]).
Regarding claims 130-132, Kim further teaches the addition of a biocompatible material linked to the peptide (substance with activity to a glucagon receptor). The biocompatible material can be selected from the group consisting of polyethylene glycol, fatty acid, cholesterol, albumin and a fragment thereof, an albumin-binding material, a polymer of repeating units of a particular amino acid sequence, an antibody, an antibody fragment, an FcRn binding material, in vivo connective tissue or a derivative thereof, a nucleotide, fibronectin, transferrin, a saccharide, and a polymer ([0137]). Further, the FcRn-biding material is characterized in that it is a polypeptide including an immunoglobulin Fc region ([0140]).
Regarding claims 133-135, Kim further teaches that the biocompatible material can be linked by a linker selected from polyethylene glycol, polypropylene glycol, an ethylene glycol-propylene glycol copolymer, polyoxyethylated polyol, polyvinyl alcohol, a polysaccharide, dextran, polyvinyl ethyl ether, a biodegradable polymer such as polylactic acid (PLA) and polylacticglycolic acid (PLGA), lipid polymer, chitin, hyaluronic acid, fatty acid, a polymer, a low molecular weight compound, a nucleotide, and a combination thereof ([0138]).
Regarding claim 136, Kim further teaches that the biocompatible material can be an immunoglobulin Fc region that is aglycosylated; selected from the group consisting of a) a CH1-4 domain, b) a CH1 and a CH2 domain, c) a CH1 and CH3 domain, d) a CH2 and CH3 domain, e) a combination between one or two or more domains among a CH1-4 domain and an immunoglobulin hinge region or part of the hinge region, and f) a dimer between each domain of the heavy chain constant region and the light chain constant region; is a dimer; is a native Fc derivative in which the region capable of forming a disulfide bond is deleted, a native Fe derivative in which a part of the amino acid(s) in the N-terminus is deleted, a native Fc derivative in which a methionine is added to the N-terminus, a native Fc derivative in which a complement-binding site is deleted, or a native Fc derivative in which an antibody dependent cell mediated cytotoxicity (ADCC) site is deleted; is derived from an immunoglobulin selected from the group consisting of IgG, IgA, IgD, IgE, and IgM; is an IgG4 Fc; or is an aglycosylated Fc region derived from human IgG4 ([0141-0153]).
Regarding claim 137, Kim further teaches that the non-peptide linker can be linked to the cysteine residue of a peptide. The non-peptide linker can also be characterized in that both ends of the nonpeptide linker are respectively linked to an amine group or a thiol group of a peptide, which includes the amino acid sequence of General Formula 1 and a biocompatible material ([0154-0155]).
Regarding claim 139, as stated above, Rauch teaches administration of an SLGT-2 inhibitor such as dapagliflozin, canagliflozin, remogliflozin, or sergliflozin (Pg 21, lines 4-17).
Regarding claim 140, Kim further teaches that metabolic syndrome is characterized in that it is selected from the group consisting of impaired glucose tolerance, hypercholesterolemia, dyslipidemia, obesity, diabetes, hypertension, nonalcoholic steatohepatitis (NASH), atherosclerosis caused by dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease, and stroke ([0156]).
Second rejection
Claim(s) 100, 126-129, and 139-140 rejected under 35 U.S.C. 103 as being unpatentable over Jung et al. (US 2014/0128318 A1, published 5/8/2014) in view of Unson et al. (Positively charged residues at positions 12, 17, and 18 of glucagon ensure maximum biological potency. J Biol Chem. 1998 Apr 24;273(17):10308-12.) and Riber et al. (WO 2016166289 A1, published 10/20/2016).
Jung teaches peptides and methods of treating obesity (Abstract). Jung teaches that obesity is a metabolic disease (metabolic syndrome) that affects the whole body, and increases the risk for diabetes, hyperlipidemia, sexual dysfunction, arthritis, cardiovascular diseases, and in some cases cancer ([0109]). Jung teaches pharmaceutical compositions that are administered for the treatment of obesity, comprising a step of administering to a subject a peptide, which can be administered alone or in combination or coincident with other pharmaceutical formulations showing prophylactic or therapeutic effects on obesity (claims 1, 11, 13).
One such peptide taught is SEQ ID NO: 31, which consists of the following sequence: Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Glu Lys Arg Ala Lys Glu Phe Val Gln Trp Leu Met Asn Thr Cys, wherein Xaa at position two is Aib (Sequence Listing, Pg 17).
Jung further teaches that peptides of the invention can have one or more amino acid pairs at positions 10 and 14, 12 and 16, 16 and 20, 20 and 24, and 24 and 28 of the amino acid sequence substituted with glutamic acid or lysine to form rings ([0046], claims 5 and 6). Jung explains that the peptide sequence can be substituted with to help further stabilize the alpha helical structure. Although not explicitly included, SEQ ID NO: 31 of Jung has a Glu at position 16 and a Lys at position 20, which could facilitate the formation of ring between these residues to further stabilize the protein structure.
Jung does not teach a variant of SEQ ID NO: 31 wherein position 17 is Arg nor treating metabolic syndrome.
Unson teaches that Lys12, Arg17, and Arg18 of glucagon have large effects on receptor binding and transduction of hormonal signal and contribute strongly to the stabilization of the binding interaction with the glucagon receptor that leads to maximum biological potency (Abstract).
Riber teaches materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders, including metabolic syndrome (Abstract; Pg 12, lines 34-36). The method comprises administering a glucagon-derivative in combination with another therapy, such as an agent for treatment of obesity, hypertension, dyslipidemia, or diabetes (Pg 16, line 24-25); examples of anti-diabetic agents include a biguanide (e.g., metformin), a sulfonylurea, a meglitinide, an SGLT2 inhibitor, (i.e., an inhibitor of sodium-glucose transport, e.g., a gliflozin such as empagliflozin, canagliflozin, dapagliflozin, or iprgagliflozin) (Pg 17, lines 9-15).
Riber teaches that the underlying risk factor for metabolic syndrome is abdominal obesity (Pg 12, line 8). Riber further teaches that the compounds in the combination therapy can be given together or separately (Pg 16, lines 27-28).
Thus, regarding claims 100 and 126-129, Jung teaches a method of treating obesity in a subject in need thereof comprising co-administering a peptide such as SEQ ID NO: 31, the structure of which can be further stabilized through the formation of one or more intramolecular ring(s), such as between glutamic acid and lysine and at positions 16 and 20, and another pharmaceutical formulation that has therapeutic effects on obesity. Unson teaches that having Arg at position 17 of glucagon is useful to maximize its biological potency. Thus, it would be prima facie obvious to substitute the Lys at position 17 of SEQ ID NO: 31 taught by Jung for Arg as taught by Unson, thereby arriving at the instant SEQ ID NO: 37, in order to maximize the potency of the peptide and improve treatment efficacy. One skilled in the art would have a reasonable expectation of success as it was already established that the presence of Arg at position 17 substantially impacts glucagon interaction with its receptor.
Further, Riber teaches a method of treating metabolic syndrome, obesity, and other associated disorders through administration of a combination of a glucagon-derivative and another therapy such as an agent for treatment of obesity, hypertension, dyslipidemia, or diabetes. Thus, it would be prima facie obvious to use the method taught by Jung and Unson to treat obesity and, by extension, metabolic syndrome, in order to maximize weight loss and its associated improvements to metabolic syndrome. One skilled in the art would have a reasonable expectation of success as Riber established that a combination of a glucagon-derived peptide coadminsitered wither another agent for the treatment of obesity, hypertension, dyslipidemia, or diabetes, could successfully treat metabolic syndrome.
Additionally, combining equivalents known for the same purpose is prima facie obvious. Per MPEP 2144.06(I), "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). By extension of this logic, it would be obvious to coadminister two therapeutics known to treat metabolic syndrome at the same time, such as SEQ ID NO: 37 taught by Jung and Unson and any of those taught by Riber.
Regarding claim 139, Riber teaches examples of SGLT2 inhibitors include empagliflozin, canagliflozin, dapagliflozin, or iprgagliflozin (Pg 17, lines 9-15).
Regarding claim 140, Riber teaches treating obesity, impaired glucose tolerance, hypercholesterolemia (metabolic syndrome is characterized by atherogenic dyslipidemia, which includes high LDL; see Pg 11, line 37 – Pg 12, line 8), dyslipidemia, diabetes, hypertension, atherosclerosis, arteriosclerosis, coronary heart disease, and stroke (Pg 3, line 37 – Pg 4, line 7).
Claim(s) 100, 126-135, 137, and 139-140 are rejected under 35 U.S.C. 103 as being unpatentable over Jung et al. (US 2014/0128318 A1, published 5/8/2014), Unson et al. (Positively charged residues at positions 12, 17, and 18 of glucagon ensure maximum biological potency. J Biol Chem. 1998 Apr 24;273(17):10308-12.), and Riber et al. (WO 2016166289 A1, published 10/20/2016), as applied to claims 100, 126-129, and 139-140 above, and further in view of Han et al. (CN 108341880 A, published 7/31/2018).
The teachings of Jung, Unson, and Riber have been set forth above. Jung, Unson, and Riber do not teach linking a biocompatible material to SEQ ID NO: 37 (the substance with activity to a glucagon receptor). Per the instant specification, a biocompatible material refers to a material linked to the biologically active substance (e.g., the substance with activity to a glucagon receptor or insulinotropic peptide) to extend the duration of effects of the biologically active substance compared with the biologically active substance to which the biocompatible material or carrier is not linked (see instant [00640]).
Han teaches chimeric polypeptides comprising GLP-1 and glucagon fragment analogs as well as conjugates and polymers (Abstract). More specifically, Han teaches that polypeptide hormones are targeted for enzymatic degradation and renal clearance, which is one of the main factors affecting in vivo half-life. Conjugates comprising polyethylene glycol (PEG) can slow renal clearance and effectively prolong the biological half-life ([0052-0054]).
Thus, regarding claims 130-132, Jung, Unson, and Riber teach a method of treating obesity and metabolic syndrome in a subject in need thereof comprising administering SEQ ID NO: 37. Han teaches that attaching PEG to polypeptide hormones improves their half-life. Thus, it would be prima facie obvious to attach PEG to the instant SEQ ID NO: 37 in order to improve its half-life. One skilled in the art would have a reasonable expectation of success as it was already established that this approach could improve the half-life of other glucagon derivatives.
Regarding claims 133-135, Han also teaches that an effective way to prolong the in vivo half-life of a polypeptide is to dimerize or multimerize it. Dimers can be formed through a linker such as double maleimide-polyethylene glycol (Mal-PEG-Mal) (claim 6).
Regarding claim 137, Han further teaches that a Cys residue at position X30 can be covalently conjugated to PEG through the Cys sulfhydryl side chain ([0052-0054]).
Claim(s) 100, 126-137, and 139-140 are rejected under 35 U.S.C. 103 as being unpatentable over Jung et al. (US 2014/0128318 A1, published 5/8/2014), Unson et al. (Positively charged residues at positions 12, 17, and 18 of glucagon ensure maximum biological potency. J Biol Chem. 1998 Apr 24;273(17):10308-12.), Riber et al. (WO 2016166289 A1, published 10/20/2016), and Han et al. (CN 108341880 A, published 7/31/2018), as applied to claims 100, 126-135, 137, and 139-140 above, and further in view of Kim et al. (KR 20170049320 A, published 5/10/2017).
The teachings of Jung, Unson, Riber, and Han have been set forth above. Jung, Unson, Riber, and Han do not teach attaching a biocompatible material such as an immunoglobulin Fc region.
Kim teaches a dual function protein with improved pharmacological efficacy, in vivo duration and stability as a biologically active protein and an FGF21 mutant protein are bonded to an Fc region of an immunoglobulin, which can be used as an effective therapeutic agent for diabetes, obesity, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver diseases, non-alcoholic steatohepatitis or cardiovascular diseases (Abstract). The Fc region can be any one of IgG1-5 Fc regions or a hybrid Fc region consisting of a combination of these. The hybrid region may also include an IgG4 region and an IgD region. It may also comprise a portion of the hinge sequence of the IgD Fc and CH2, and CH2 and CH3 sequences of the IgG4 Fc ([0048]).
Thus, regarding claim 136, Jung, Unson, Riber, and Han teach attachment of biocompatible materials to the instant SEQ ID NO: 37 in order to prolong in vivo half-life. Kim teaches that one method to improve the pharmacological efficacy, in vivo duration and stability of a peptide is to attach the peptide therapeutic to an immunoglobulin Fc region. Thus, it would be prima facie obvious to attach an immunoglobulin Fc region, such as the one derived from IgG, to the instant SEQ ID NO: 37 in order to improve its half-life. One skilled in the art would have a reasonable expectation of success as it was already established that this approach could improve the half-life of other incretin derivatives, including glucagon.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 100, 126-135, and 140 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5-10 of U.S. Patent No. 11,667,688 (US ‘688). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of US ‘688 recites a method for treating metabolic syndrome, comprising administering (i) an isolated peptide or (ii) an isolated conjugate in which the isolated peptide is linked to a biocompatible material capable of increasing in vivo half-life, to a subject in need thereof, wherein the peptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 20, 22, 27, and 37, wherein the metabolic syndrome is selected from the group consisting of impaired glucose tolerance, hypercholesterolemia, dyslipidemia, obesity, hypertension, nonalcoholic steatohepatitis (NASH), atherosclerosis caused by dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease, and stroke. Dependent claim 3 similarly recites that a method of treating comprising administering an isolated peptide or conjugate of SEQ ID NO: 37. SEQ ID NO: 37 of US ‘688 and the instant SEQ ID NO: 37 are identical.
Other dependent claims include administering a compound or material having therapeutic activity for metabolic syndrome before or after administration of the isolated peptide or conjugate (claim 8), the types of compounds or materials having therapeutic activity for metabolic syndrome (claims 9 and 10), and the identities of the biocompatible material (claims 5 and 7) and linker connecting the biocompatible material to the peptide (claim 6).
Claims 100, 126-131, 133-134, and 140 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5-18, and 21-27 of U.S. Patent No. 10,696,725 (US ‘725). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Dependent claim 1 of US ‘725 recites an isolated peptide comprising the amino acid sequence of the following General Formula 2: (General Formula 2, SEQ ID NO: 46) Y-Aib-QGTF-X7-SD-X10-S-X12-Y-L-X15-X16-X17-R-A- X20-X21-F-V-X24-W-L-M-N-T-X30
wherein, X7 is threonine, valine, or cysteine; X10 is tyrosine or cysteine; X12 is lysine or cysteine; X15 is aspartic acid or cysteine; X16 is glutamic acid or serine; X17 is lysine or arginine; X20 is glutamine or lysine; X21 is aspartic acid or glutamic acid; X24 is valine or glutamine; and X30 is cysteine or is absent, with the proviso that a peptide of the amino acid sequence of SEQ ID NO: 12 is excluded. The instant SEQ ID NO: 37 meets the limitations of claim 1 of US ‘725, wherein X7 is threonine, X10 is tyrosine, X12 is lysine, X15 is aspartic acid, X16 is glutamic acid, X17 is arginine, X20 is lysine, X21 is glutamic acid, X24 is glutamine, and X30 is cysteine. Dependent claim 5 recites the peptide of claim 1, wherein the peptide comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 13, 15, 19, 33, and 36 to 44; dependent claim 14 recites the method of claim 13, wherein (i) the peptide or (ii) the conjugate comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 13, 15, 19, 33, and 36 to 44; dependent claim 15 recites a pharmaceutical composition comprising these peptides or conjugates and at least one compound or material having a therapeutic activity for metabolic syndrome; and dependent claim 16 recites the pharmaceutical composition of claim 15, wherein the isolated peptide comprises the amino acid selected from the group consisting of SEQ ID NO: 13, 15, 19, 33, and 36 to 44. SEQ ID NO: 37 of US ‘725 and the instant SEQ ID NO: 37 are identical.
Dependent claims further include formation of a ring between the amino acid pair X16 and X20, which are respectively glutamic acid and lysine (claim 2), an isolated conjugate of the peptide and a biocompatible material capable of increasing half-life linked to the peptide (claim 6), identities of the biocompatible material (claims 7 and 10) and linker connecting the biocompatible material to the peptide (claims 8 and 9), a composition comprising the peptide or conjugate with or without additional compounds or materials having a therapeutic activity for metabolic syndrome (claims 11 and 15), a method for treating metabolic syndrome with or without additional compounds or materials having a therapeutic activity for metabolic syndrome (claims 13, 21 and 25-27), a method for treating hypoglycemia with or without additional compounds or materials having a therapeutic activity for hypoglycemia (claims 22-24), the types of compounds or materials having therapeutic activity for metabolic syndrome (claims 17 and 18).
Claims 100, 126-137, and 139-140 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-19, and 21-22 of U.S. Patent No. 11,142,559 (US ‘559) in view of Rauch et al. (WO2013167554A1, published 11/14/2013). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of US ‘559 recites a method for treating congenital hyperinsulinism comprising administering to a subject in need thereof, an isolated conjugate comprising a peptide moiety and a biocompatible material moiety which is linked to the peptide moiety, wherein the peptide moiety comprises the amino acid sequence of the following General Formula 2: (SEQ ID NO: 46) Y-Aib-QGTF-X7-SD-X10-S-X12-Y-L-X15-X16-X17-R-A- X20-X21-F-V-X24-W-L-M-N-T-X30 General Formula 2, wherein X7 is threonine (T), valine (V), or cysteine (C); X10 is tyrosine (Y) or cysteine (C); X12 is lysine (K) or cysteine (C); X15 is aspartic acid (D) or cysteine (C); X16 is glutamic acid (E) or serine (S); X17 is lysine (K) or arginine (R); X20 is glutamine (Q) or lysine (K); X21 is aspartic acid (D) or glutamic acid (E); X24 is valine (V) or glutamine (Q); and X30 is cysteine (C) or is absent, with the proviso that the amino acid sequence of General Formula 2 identical to SEQ ID NO: 12 is excluded. The instant SEQ ID NO: 37 meets the limitations of claim 1 wherein X7 is threonine (T); X10 is tyrosine (Y); X12 is lysine (K); X15 is aspartic acid (D); X16 is glutamic acid (E); X17 arginine (R); X20 is lysine (K); X21 is glutamic acid (E); X24 is glutamine (Q); and X30 is cysteine (C). Dependent claim 3 of US ‘559 recites that the peptide moiety is selected from SEQ ID NO: 13, 15, and 36 to 44. SEQ ID NO: 37 of US ‘559 and the instant SEQ ID NO: 37 are identical.
The specification of US ‘559 indicates that the compositions containing glucagon derivatives or conjugates used for preventing or treating congenital hyperinsulinism can also be used to prevent or treat metabolic syndrome (Col. 3, lines 49-54).
Claim 2 of US ‘559 similarly recites a method for treating congenital hyperinsulinism comprising administering to a subject in need thereof, an isolated conjugate comprising a peptide moiety and a biocompatible material moiety which is linked to the peptide moiety, wherein the peptide moiety comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 2 to 11, 13 to 15, and 18 to 44, and dependent claim 13 of US ‘559 recites that the peptide moiety is selected from SEQ ID NO: 13, 15, and 36 to 44.
Dependent claims further include identities of the biocompatible material (claims 4, 5, 9, 15, 18, 19) and linker connecting the biocompatible material to the peptide (claims 6-8, 14, 16, 17) and the means through which the linker is connected to the peptide moiety and the biocompatible material (claims 11-12 and 21-22).
US ‘559 does not teach co-administering a compound or substance with therapeutic activity against metabolic syndrome.
As stated above, Rauch teaches administering a pharmaceutical composition comprising a combination of therapeutics, wherein at least one is selected from GPR1 agonists (G protein-coupled agonists), biguanides, sulfonylureas, metiglinides, thiazolidinediones, α-glucosidase inhibitors, and/or SGLT 2 inhibitors; administering such combinations provides several advantages, described above.
Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Rauch into US ‘559, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Rauch teaches that combination therapies can create improved therapeutic outcomes while reducing potential toxicities associated with any one individual therapeutic. Thus, the above claims are rendered obvious in light of the teachings of US ‘559.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658