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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4/13/2026 has been entered.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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 4/13/2026 have been fully considered but they are not persuasive.
Applicant’s position is 1) there is no basis for one of ordinary skill in the art to select SEQ ID NO: 11 of Karsdal as the starting point for modification, 2) there is no motivation to introduce Aib at position 8 based upon the teachings of Karle, 3) there is no motivation to introduce a lysine conjugated to an acyl group at position 19 based upon the teachings of Suva and Ekwuribe, and 4) the teachings of Madsen and Mehta do not remedy the deficiencies of the above references.
Regarding 1), Applicant states that structural similarity to claimed compounds is insufficient motivation to select a compound as a starting material that is subsequently further modified; moreover, the prior art must identify the pertinent properties that would have guided one skilled in the art toward that specific compound (Remarks, Pg 11). This is unpersuasive because Karsdal teaches calcitonin and variants thereof exhibit anti-diabetes effects (see Pg 4, line 16 – Pg 9, line 14 of Karsdal), which is also the focus of the instant application. Additionally, one skilled in the art would recognize that peptide structure necessarily imparts peptide function; therefore, by selecting a calcitonin mimetic, such as SEQ ID NO: 11 as taught by Karsdal, one skilled in the art would expect that this starting compound would retain the properties of calcitonin.
Regarding 2 and 3), per MPEP 2143: The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. In Ball Aerosol v. Ltd. Brands, 555 F.3d 984, 89 USPQ2d 1870 (Fed. Cir. 2009), the Federal Circuit offered additional instruction as to the need for an explicit analysis. The Federal Circuit explained that the Supreme Court’s requirement for an explicit analysis does not require record evidence of an explicit teaching of a motivation to combine in the prior art.
"[T]he analysis that "should be made explicit" refers not to the teachings in the prior art of a motivation to combine, but to the court’s analysis. . . . Under the flexible inquiry set forth by the Supreme Court, the district court therefore erred by failing to take account of ‘the inferences and creative steps,’ or even routine steps, that an inventor would employ and by failing to find a motivation to combine related pieces from the prior art." Ball Aerosol, 555 F.3d at 993, 89 USPQ2d at 1877.
In the instant case, Karsdal teaches SEQ ID NO: 11, a calcitonin variant comprising the instant SEQ ID NO: 13; the only differences between SEQ ID NO: 11 of Karsdal and the instant SEQ ID NO: 13 is that position 8 is not Aib and position 19 is not Lys conjugated to an acyl group.
Regarding position Aib at position 8, Karsdal also teaches a predicted alpha helix stemming from residues 8-18 or 8-22, which is normally occupied by a methionine or a valine residue. As the predicted alpha helix begins at residue 8, one skilled in the art would be motivated to introduce an alpha-helix-stabilizing residue at this position. Karle teaches stabilization of alpha helices through introduction of the residue Aib. Thus, it would be obvious to introduce Aib into position 8 in order to provide further stability to the alpha helix that naturally occurs in calcitonin.
The Applicant states that Karle teaches that Aib can also destabilize alpha helices in addition to stabilizing them, depending on the sequence (see Remarks, Pg 12-13, “Second, Karsdal provides no suggestion…). However, it would still be obvious to try introducing Aib into position 8 to further stabilize the alpha helix of calcitonin. At the time of filing, the art recognized that calcitonin comprises an alpha helix that begins at residue 8. The prior art – Karle – also teaches that Aib has alpha helix forming properties. One of ordinary skill in the art would have recognized that, regardless of the stability or instability of the naturally occurring calcitonin alpha helix, the introduction of Aib into position 8 would likely promote the formation of the alpha helix. Therefore, one would have been motivated to try, thereby resulting in the instant peptide SEQ ID NO: 13. See MPEP 2143(I)(E).
Regarding position 19, Suva teaches modification of calcitonin wherein the leucine is substituted for lysine conjugated to an acyl group. Suva teaches that substitution of this leucine to a lysine conjugated to p-benzoylbenzoyl; this substitution does not adversely impact calcitonin interactions with its receptor.
The Applicant states that Suva teaches multiple locations wherein leucine is substituted for lysine conjugated to p-benzoylbenzoyl, specifically positions 8, 16, and 19 (see Remarks, Pg 14, “Suva does not provide motivation to select position 19,” third paragraph; Suva, Abstract). However, one would select position 19 out of the possible positions taught by Suva as Karsdal teaches that the alpha helical region comprises at least residues 8-18, as described above. Thus, one would be motivated to select the position taught by Suva that would not interfere with the formation of said alpha helix that occurs at residues 8-18 of calcitonin, namely position 19.
Additionally, based on the teachings of Ekwuribe, one would further be drawn to select and modify leucine at position 19 for lysine attached to an acyl group because Ekwuribe teaches that calcitonin modifications at the naturally-occurring lysine residues 11 and 18 result in improved calcitonin bioavailability. Knowing this information, one skilled in the art would recognize the potential to try to modify position 19 of calcitonin by introducing a lysine (which Suva established does not impede its ability to engage its receptors), which occurs at approximately the same relative location as the acyl-conjugated lysine 18 modification in calcitonin. Thus, the combined teachings of Suva and Ekwuribe in view of Karsdal provide motivation to try to substitute the leucine at position 19 for lysine with an acyl moiety as instantly claimed; see MPEP 2143(I)(E).
Regarding 4), the Applicant states that one skilled in the art would not look to Madsen to further modify the instant peptide and Madsen does not provide motivation to arrive at the composition of the instant claims. Although it is acknowledged that Madsen teaches GLP-1 variants and mimetics rather than calcitonin ones, one skilled in the art would still look to Madsen. In this particular instance, Madsen is useful in that it teaches linker compounds designed to connect a peptide therapeutic and an acyl group. One skilled in the art seeking to connect a peptide therapeutic to an acyl group would search the prior art for similar linker compounds that had previously been shown to achieve these goals. Thus, there is motivation to combine Madsen with the above references.
Additionally, with regards to the argument that Mehta does not address the fundamental structural requirements of claim 4: in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Thus, rejection of the claims under 35 U.S.C. 103 have been maintained/modified herein below.
Claim Status
Claims 4-8 and 58-73 are pending under examination. Claims 1-3 and 9-57 cancelled. Claims 59-73 are new.
Priority
This application is the 371 of PCT/EP2019/072533, filed on 8/22/2019, which claims priority to GB1813678.8, filed on 8/22/2018. The priority date of 8/22/2018 is acknowledged.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specifically, the file size must be listed in bytes rather than kilobytes.
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.
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.
Claim(s) 4-8, 63-66, 68-69, and 71-72 are rejected under 35 U.S.C. 103 as being unpatentable over Karsdal et al. (WO 2010/103045 A1, published 9/16/2010), Karle (Karle IL. Controls exerted by the Aib residue: helix formation and helix reversal. Biopolymers. 2001;60(5):351-65.), Suva et al. (Suva LJ, Flannery MS, Caulfield MP, Findlay DM, Jüppner H, Goldring SR, Rosenblatt M, Chorev M. Design, synthesis and utility of novel benzophenone-containing calcitonin analogs for photoaffinity labeling the calcitonin receptor. J Pharmacol Exp Ther. 1997 Nov;283(2):876-84.), and Ekwuribe et al. (US 6713452, published 3/30/04).
Karsdal teaches enterally administered calcitonin family members that are effective at treating Type I or Type II diabetes or metabolic syndrome in addition to mitigating insulin resistance and reducing serum glucose levels (Abstract). Karsdal teaches SEQ ID NO 11: CX1X2LSTCX3LX4X5X6X7X8X9X10X11X12X13X14X15X16X17X18X19X20X21GX22X23X24P,
wherein
X1 is A, G, or S; preferably S;
X2 is N or S; preferably N;
X3 is M or V; preferably V;
X4 is G or S; preferably G;
X5 is T, K, or A; preferably T or K; most preferably K;
X6 is L or Y; preferably L;
X7 is T, S, or W; preferably T or S; most preferably S;
X8 is Q, K, or R; preferably Q;
X9 is D, E, or N; preferably D or E; most preferably E;
X10 is F or L; preferably L;
X11 is N or H; preferably H;
X12 is K or N; preferably K;
X13 is F or L; preferably L;
X14 is H or Q; preferably Q;
X15 is T or R; preferably T;
X16 is F or Y; preferably Y;
X17 is p or S; preferably P;
X18 is Q, G or R; preferably Q or R; most preferably R;
X19 is T, I or M; preferably T;
X20 is A, N, D, S, or G; preferably N;
X21 is I, T, V or F; preferably T,
X22 is V, S, A, or P; preferably V, S, or A; most preferably S;
X23 is G or E; preferably G;
X24 is A or T; preferably T (Pg 12-13).
This reads on the instant SEQ ID NO: 13 wherein,
X1 (position 2, or X2 of the instant SEQ ID NO: 13) is A, G, or S;
X2 (X3) is N; X4 is G; X5 (X11) is T, or A; X6 (X12) is L or Y; X7 (X13) is T, S, or W; X8 (X14) is K, or R; X9 (X15) is D, E, or N; X10 (X16) is F or L; X11 (X17) is N or H; X12 (X18) is K or N; preferably K; X14 (X20) is H; X15 (X21) is T or R; X16 (X22) is F or Y; X17 (X23) is P or S; X18 (X24) is Q, G or R; X19 (X25) is T, I or M; X20 (X26) is A, N, S, or G; X21 (X27) is I, V or F; X22 (X29) is V, A, or P; X23 (X30) is E; and X24 (X31) is A.
Karsdal also teaches that calcitonin family members share a significant degree of sequence homology and structural similarities, including a region of predicted amphipathic alpha-helical structure from residues 8-18 or 8-22 (Pg 14, lines 19-25).
Karsdal does not teach that X3 (position 8 or X8 of the instant SEQ ID NO: 13) is Aib nor that X13 (X19 of instant SEQ ID NO: 13) is K comprising an acyl group, wherein the acyl group comprises a C16 or longer fatty acid or fatty diacid.
Karle teaches that the helix forming properties of Aib have been demonstrated in numerous crystal structure analyses of designed and naturally occurring peptides containing one or more Aib residues (Abstract); with rare exceptions, the presence of an Aib residue causes the backbone of a protein or peptide to fold into a 310, mixed 310-α, or α-helix. The helix-forming propensity of Aib has been shown to be strong enough to overcome disruptive residues in a sequence, such as Pro and Hyp residues, Gly-Gly segments, d-Ala-Gly segments, and even a β-residue-γ-residue segment (Pg 351 – 352, “Helix-Forming Propensity by Dialkyl Glycines”; Pg 360, “Conclusions”).
Suva teaches substitution of Leu at position 19 of salmon calcitonin for Lys(epsilon-p-benzoylbenzoyl) does not reduce its ability to engage receptors (Abstract; Pg 881, left column, first paragraph).
Ekwuribe teaches a mixture of conjugates in which each conjugate in the mixture comprises a calcitonin drug coupled to an oligomer that includes a polyalkylene glycol moiety. The mixture may be more effective at surviving an in vitro model of intestinal digestion than non-conjugated calcitonin. Furthermore, the mixture may exhibit a higher bioavailability than non-conjugated calcitonin (Abstract). The oligomer may comprise one or more other moieties including, but not limited to, additional hydrophilic moieties, lipophilic moieties, spacer moieties, linker moieties, and terminating moieties. (Col. 8, lines 45-51). The lipophilic moiety is preferably a saturated or unsaturated, linear or branched alkyl moiety or a saturated or unsaturated, linear or branched fatty acid moiety. When the lipophilic moiety is a fatty acid moiety, it is preferably a natural fatty acid moiety that is linear, saturated or unsaturated, having 2 to 18 carbon atoms (Col. 9, lines 16-29). Examples 41-44 further describe the process whereby oligomers are conjugated to salmon calcitonin, including stearate-PEG6-sCT (wherein PEG6 is a linker and stearate corresponds to C18 fatty acid) and stearate-PEG8-sCT (wherein PEG8 is a linker and stearate corresponds to C18 fatty acid; Col. 62 line 29 -59). The oligomer and additional moiety may be conjugated to lysine residues within the peptide sequence (Col. 11, lines 6-14).
Thus, regarding position 8 of the instantly claimed SEQ ID NO: 13, Karsdal teaches the calcitonin variant SEQ ID NO: 11, which includes an alpha helix at positions 8-18 or 8-22. Karle teaches that Aib can initiate helix formation. Therefore, it would be prima facie obvious to incorporate Aib into position 8 of the calcitonin variant taught by Karsdal in order to further stabilize the helical structure of the calcitonin variant. One skilled in the art would have a reasonable expectation of success as it was already established that Aib could initiate and stabilize helical protein structures.
Additionally, based on the above prior art teachings, it would be obvious to try introducing Aib into position 8 to further stabilize the alpha helix of calcitonin. At the time of filing, the art recognized that calcitonin comprises an alpha helix that begins at residue 8. The prior art – Karle – also teaches that Aib has alpha helix forming properties. One of ordinary skill in the art would have recognized that, regardless of the stability or instability of the naturally occurring calcitonin alpha helix, the introduction of Aib into position 8 would likely promote the formation of the alpha helix. Therefore, one would have been motivated to try, thereby resulting in the instant peptide SEQ ID NO: 13 with Aib at position 8. See MPEP 2143(I)(E).
Regarding position 19 of the instantly claimed SEQ ID NO: 13, Suva teaches modification of calcitonin wherein the leucine is substituted for lysine conjugated to an acyl group. Suva teaches that substitution of this leucine to a lysine conjugated to p-benzoylbenzoyl; this substitution does not adversely impact calcitonin interactions with its receptor.
Although Suva teaches multiple locations wherein leucine is substituted for lysine conjugated to p-benzoylbenzoyl, specifically positions 8, 16, and 19 (Abstract), one would select position 19 out of the possible positions taught by Suva as Karsdal teaches that the alpha helical region comprises at least residues 8-18, as described above. Thus, one would be motivated to select the position taught by Suva that would not interfere with the formation of said alpha helix that occurs at residues 8-18 of calcitonin, namely position 19.
Additionally, Ekwuribe further teaches calcitonin mimetics improved by the addition of polyalkylene glycol moiety conjugated to lipid moieties including C18 fatty acids, which can be conjugated to lysine residues in the peptide sequence. Based on the teachings of Ekwuribe in view of Suva, one would further be drawn to select and modify leucine at position 19 for lysine attached to an acyl group because Ekwuribe teaches that calcitonin modifications at the naturally-occurring lysine residues 11 and 18 result in improved calcitonin bioavailability. Knowing this information, one skilled in the art would recognize the potential to try to modify position 19 of calcitonin by introducing a lysine (which Suva established does not impede its ability to engage its receptors), which occurs at approximately the same relative location as the acyl-conjuated lysine 18 modification in calcitonin. Thus, the combined teachings of Suva and Ekwuribe in view of Karsdal provide motivation to try to substitute the leucine at position 19 for lysine with an acyl moiety as instantly claimed; See MPEP 2143(I)(E).
Thus, the above teachings render the instant claims regarding claims 4, 6, 7, 8, and 68 obvious.
Regarding claims 5 and 63, Karsdal, Suva, Ekwuribe, and Karle do not teach introduction of Ala to positions 14 or 20, respectively. However, as stated above, one skilled in the art would recognize that calcitonin comprises an alpha helix from residues 8-18 or 8-22 depending on the species, which imparts its functionality. As these positions are typically occupied by Q, K, or R (position 14) and H or Q (position 20) per Karsdal, it would be obvious to one skilled in the art to substitute the residues at these positions for Ala residues in order to further stabilize the alpha helix structure and, by extension, the peptide.
Regarding claim 69, Ekwuribe teaches pharmaceutical compositions suitable for oral administration (Col. 45, lines 24-30), parenteral administration (Col. 45, lines 58-62), and injection (Col. 46 lines 1-6).
Regarding 64, Karsdal teaches mimetics that include N-terminal acetylation (Pg 42, lines 1-9).
Regarding claims 65 and 66, Karsdal teaches that calcitonin family members share a significant degree of sequence homology and structural similarities, including a disulfide bridged loop of 6 or 7 amino acids at the N-terminus and a C-terminally amidated aromatic residue at the C-terminus (Pg 14, lines 19-25).
Regarding claims 71 and 72, Karsdal teaches suitable pharmaceutical carriers such as 5-CNAC, SNAD, and SNAC (Pg 24, lines 17-24).
Claim(s) 4-8, 58-61, 63-69, and 71-73 are rejected under 35 U.S.C. 103 as being unpatentable over Karsdal et al. (WO 2010/103045 A1, published 9/16/2010), Karle (Karle IL. Controls exerted by the Aib residue: helix formation and helix reversal. Biopolymers. 2001;60(5):351-65.), Suva et al. (Suva LJ, Flannery MS, Caulfield MP, Findlay DM, Jüppner H, Goldring SR, Rosenblatt M, Chorev M. Design, synthesis and utility of novel benzophenone-containing calcitonin analogs for photoaffinity labeling the calcitonin receptor. J Pharmacol Exp Ther. 1997 Nov;283(2):876-84.), and Ekwuribe et al. (US 6713452, published 3/30/04), as applied to claims 4-8, 63-66, 68-69, and 71-72 above, and further in view of Madsen et al. (US2013/0288960 A1, filed 11/9/11, published 10/31/13).
The teachings of Karsdal, Karle, Suva, and Ekwuribe have been set forth above. Karsdal, Karle, Suva, and Ekwuribe do not teach a linker comprising an E and/or an OEG amino acid linker.
Madsen teaches derivatives of GLP-1 to treat diabetes, which comprise a first and second K residue comprising protracting moieties, preferably selected from fatty diacids or fatty acids, attached to said K residues to improve receptor binding and half-life, conjugated via a linker, wherein the linker comprises Chem. 4:
PNG
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96
356
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Greyscale
, wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5 (Abstract; [0079], [0120-0129]). When k=1 and n=1, the linker element may be designated OEG ([0080]).
Madsen teaches that, in certain embodiments, a GLP-1 derivative may have a linker that consists of two times Chem. 4, interconnected via an amide bond, the linker being connected at it’s *-NH end to the *-CO end of the protracting moiety (fatty acid or diacid) and at it’s *-CO end to the ε amino group of the first or the second K residue of the GLP-1 analogue (Pg 6, first column, “c”).
Thus, regarding claims 58-61, Karsdal, Karle, Suva, and Ekwuribe teach a calcitonin variant with a C18 fatty acid conjugated to Lys at position 19 that can treat diabetes. Madsen teaches conjugating fatty acids and diacids to GLP-1 derivatives via the linker Chem 4 that can be used to treat diabetes. Therefore, it would be prima facie obvious to use the linker Chem 4 taught by Madsen to attach the C18 fatty acid taught by Karsdal, Karle, Suva, and Ekwuribe. One skilled in the art would have a reasonable expectation of success as it was already established that the addition of Chem 4 and fatty acid molecules to GLP-1 derivatives improved their receptor binding and half-life.
Regarding claim 67, Madsen teaches that a second linker element may follow the linker element Chem. 4:
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media_image2.png
118
330
media_image2.png
Greyscale
that may be included p times, where p is an integer in the range of 1-3. This second linker element may also be referred to as gamma-Glu (gGlu) due to the fact that it is the gamma carboxy group of the amino acid glutamic acid which is here used for connection to another linker element, or to the epsilon-amino group of lysine ([0082]).
Regarding claim 73, Madsen teaches the addition of one or more pharmacologically active substances such as antidiabetic agents, antiobesity agents, appetite regulating agents, antihypertensive agents, agents for the treatment and/or prevention of complications resulting from or associated with diabetes and agents for the treatment and/or prevention of complications and disorders resulting from or associated with obesity. Examples of which include lipase/amylase inhibitors and Gastric Inhibitory Polypeptide agonists or antagonists (GIP analogs), among others ([0180]).
Claim(s) 4-8, 62-66, 68-69, and 70-72 are rejected under 35 U.S.C. 103 as being unpatentable over Karsdal et al. (WO 2010/103045 A1, published 9/16/2010), Karle (Karle IL. Controls exerted by the Aib residue: helix formation and helix reversal. Biopolymers. 2001;60(5):351-65.), Suva et al. (Suva LJ, Flannery MS, Caulfield MP, Findlay DM, Jüppner H, Goldring SR, Rosenblatt M, Chorev M. Design, synthesis and utility of novel benzophenone-containing calcitonin analogs for photoaffinity labeling the calcitonin receptor. J Pharmacol Exp Ther. 1997 Nov;283(2):876-84.), Ekwuribe et al. (US 6713452, published 3/30/04), as applied to claims 4-8, 63-66, 68-69, and 71-72 above, and further in view of Mehta et al. (WO 2013/067357 A1, published 5/10/2013).
The teachings of Karsdal, Karle, Suva, and Ekwuribe have been set forth above. Karsdal, Karle, Suva, and Ekwuribe do not teach calcitonin mimetics wherein position X30 is N.
Mehta teaches calcitonin mimetics for the treatment of diabetes, metabolic syndrome, obesity, appetite suppression, or mitigating insulin resistance and related symptoms thereof (Abstract; Pg 1, “Field”). Mehta teaches calcitonin mimetics wherein the position equivalent to X30 is N reduce at least one of bone resorption and cartilage degradation in the patient relative to wild-type salmon calcitonin (Example 6, Pg 45; Figures 18 and 19; Table 1, Pg 7: mimetics UGP281, 283, 302, 303, 306, 1000); such calcitonin mimetics are also capable of treating the aforementioned diabetes, obesity, and metabolic syndrome diseases and/or symptoms.
Thus, regarding claim 62, it would be prima facie obvious introduce Asn to position X30 calcitonin mimetic taught by Karsdal, Karle, Suva, and Ekwuribe in order to reduce bone resorption and/or cartilage degradation. One skilled in the art would have a reasonable expectation of success as Mehta established that this substitution could impart said functionality on calcitonin mimetics.
Regarding claim 70, Mehta teaches calcitonin mimetic peptides formulated for oral administration comprising coated citric acid particles wherein the citric acid particles increases the oral bioavailability of the peptide (Claim 6, Pg 48).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sara Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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