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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/18/2026 has been entered.
Priority
This application was filed on and is a U.S. national Stage application under 35 U.S.C. 371 of International Patent Application No. PCT/KR2020/019069 filed 12/24/2020, which claims the benefit of the priority of Korean Patent Application No. KR10-2019-0174117 filed 12/24/2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
Claims 1, 7-8, 10-19 are pending. Claims 2-6, 9 are canceled. Claims 1, 7, 10-11, are amended. Claims 1, 7-8, 10-19 are being examined on the merits in this office action.
Claim Objections - Withdrawn
The objection of claim 11 is withdrawn in view of the claim amendments.
Claim Rejections - Withdrawn
The rejection of claims 1, 7-8, and 10- 19 under 35 U.S.C. 103 as being unpatentable over Kim et al. (US20140377290A1) in view of Henriksen et al. (US20070135345A1) is withdrawn in view of the claim amendments.
Claim Objections - New
Claim 11 is objected to because of the following informalities:
Claim 11 should be amended to include a space between osteocalcin and (osteocalcin) in line 3. Appropriate correction is required.
Claim Rejections - 35 USC § 112 - New
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.
Claim 11 is 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.
Regarding claim 11, the claim contain a parenthesis in line 3-4. It is unclear whether the limitations in the parenthesis are a required part of the claimed invention.
Claim Rejections - 35 USC § 103 - New
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.
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.
Claims 1, 7-8, and 10-19 are rejected under 35 U.S.C. 103 as being unpatentable over Henriksen et al. (Bone 34 (2004) 140–147) in view of Kim et al. (US20140377290A1 – hereinafter “Kim”) and Thim et al. (CA2502324A1 – hereinafter “Thim”)
Henriksen teaches a method of stimulation bone formation comprising administering GLP-2 and that the method is used for treating osteoporosis (Page 147, left col., last line). Henriksen teaches that the method revealed an accumulated increase of osteocalcin levels and a dose-dependent effect of GLP-2 on bone formation (Page 146, left col. 2nd paragraph, line 1-5; Page 147, left col., line 1-5; Fig. 4C). Further, Henriksen teaches that the method reduced bone resorption (Page 144, right col., 2nd paragraph, line 4-7), which is known to inhibit bone degradation. Examiner notes that Henriksen teaches the method for treating osteoporosis and the instant claims recite that osteoporosis is an example of metabolic bone disease, thus this limitation is met.
Henriksen does not teach the instant recited GLP-2 of SEQ ID NO: 9.
Kim teaches GLP-2 has the sequence of SEQ ID NO: 1, HADGSFSDEMNTILDNLAARDFINWLIQTKITD [0034]. Kim teaches GLP-2 derivatives such as imidazo-acetyl-GLP-2 (CA-GLP2) where an α-carbon of the first histidine residue at the N-terminal end of native GLP-2 and an N-terminal amine group linked thereto are deleted [0041]. Kim further teaches derivatives such as CA GLP-2(A2G, 34C) [0027-0030, 0105, 0108], wherein the Histidine is modified to imidazoacethyldeshistidine, second amino acid (Alanine) is substituted with Glycine and the 34th amino acid is a Cysteine. Examiner notes that the sequence of Kim reads on the instant sequence. Kim teaches methods of treating disease or conditions such as bone impairment [0089].
Examiner notes that even though Kim does not explicitly teach that the K in position 30 is substituted with an R, Kim teaches conservative amino acid substitutions and teaches that most occurring exchanges are Lys/Arg.
Further, it is known in the art to substitute the L at position 30 with an R as taught by Thim et al.
Thim teaches GLP-2 variants for treating bone related disorders such as osteoporosis, hypercalcemia of malignancy, osteopenia (Page 9 line 5-8). Thim teaches GLP-2 variants wherein the amino acid residue lysine in position 30 is exchanged with an arginine residue (Page 3, line 30-31); or that the GLP-2 variant is K30R-GLP-2), which shows that the K at position 30 is changed to R (Page 20, line 35). Thim teaches that the GLP-2 variants displayed increases stability and shelf-life (Page 10, line 23-24).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Henriksen and specifically administer the GLP-2 variant taught by Kim and Thim wherein X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is arginine, and X34 is lysine or cysteine since both Kim and Thim teach that the variants with the recited amino acid substitutions displayed prolonged in vivo half-life and an improved in vivo durability and stability (Abstract). One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using the modified GLP-2 analogue to treat bone diseases since it is generally known in the art that GLP-2 analogues were successful in treating bone diseases and all the cited references teach the use of GLP-2 variants to treat bone diseases. The disclosures render obvious claim 1.
Regarding claim 7, Kim teaches the GLP-2 peptide of SEQ ID NO: 1: HADGSFSDEMNTILDNLAARDFINWLIQTKITD [0034], and further that the GLP-2 can be modified as Imidazoacetyl GLP-2 (CA-GLP-2, A2G, 34C [0105], wherein X1 is imidazoacetyldeshistidine, X2 is substituted to Glycine (A2G) and X34 is cysteine (34C). Further, Thim teaches GLP-2 variants wherein the amino acid residue lysine in position 30 is exchanged with an arginine residue (Page 3, line 30-31); or that the GLP-2 variant is K30R-GLP-2), which shows that the K at position 30 is changed to R (Page 20, line 35). Examiner notes that when the teachings of Kim and Thim are combined, the teachings would read on the instant SEQ ID NO: 6 (XGDGSFSDEMNTILDNLAARDFINWLIQTRITDC), wherein X1 is imidazoacetyldeshistidine, X2 is G, X30 is R and X34 is C. It would have been obvious to modify Henriksen and use the variants as taught by Kim and Thim for increased stability and shelf-life.
Regarding claims 8 and 10, Henriksen teaches a method of stimulation bone formation comprising administering GLP-2 and that the method is used for treating osteoporosis (Page 147, left col., last line). Further, Thim teaches GLP-2 variants for treating bone related disorders such as osteoporosis, hypercalcemia of malignancy, osteopenia (Page 9 line 5-8).
Regarding claim 11, Henriksen teaches that the method of administering GLP-2 caused a reduction is CTX levels and caused an increase in osteocalcin (Page 145, left col., 1st paragraph).
Regarding claim 12, Henriksen teaches the method of administering GLP-2 (Abstract) and GLP-2 of Henriksen is unmodified.
Regarding claim 13, Kim teaches a glucagon-like peptide-2 (GLP-2) conjugate comprising native GLP-2 or its derivative and an immunoglobulin Fc fragment being covalently linked via a non-peptidyl polymer, and that the GLP-2 conjugate of the present invention has a remarkably increased binding affinity to a GLP-2 receptor, it shows a prolonged in vivo half-life and an improved in vivo durability and stability (Abstract; claim 24; [0012-0014, 0026]). It would have been obvious to modify Henriksen and administer the GLP-2 as a conjugate for prolonged in vivo half-life and an improved in vivo durability and stability (Abstract; claim 24; [0012-0014, 0026]).
Regarding claim 14, Kim teaches a glucagon-like peptide-2 (GLP-2) conjugate comprising native GLP-2 or its derivative and an immunoglobulin Fc fragment being covalently linked via a non-peptidyl polymer, and that the GLP-2 conjugate of the present invention has a remarkably increased binding affinity to a GLP-2 receptor, it shows a prolonged in vivo half-life and an improved in vivo durability and stability (Abstract; claim 24; [0012-0014, 0026]). Kim teaches that the one end of the non-peptidyl polymer is covalently linked to the immunoglobulin Fc fragment and the other end thereof is covalently linked to the amine group or thiol group of the GLP-2 or its derivative (claim 28), wherein the non-peptidyl polymer is selected from the group consisting of polyethylene glycol (claim 30). Examiner notes the teachings of Kim read on the instant formula of X-L-F, wherein a is 1. It would have been obvious to modify Henriksen and administer the GLP-2 as a conjugate for prolonged in vivo half-life and an improved in vivo durability and stability (Abstract; claim 24; [0012-0014, 0026]).
Regarding claim 15, Kim teaches that an aglycosylated or deglycosylated Fc fragment is preferred [0065]. It would have been obvious to modify Henriksen and administer the GLP-2 as a conjugate with Fc region for prolonged in vivo half-life and an improved in vivo durability and stability (Abstract; claim 24; [0012-0014, 0026]).
Regarding claim 16, Kim teaches that the Fc fragment modified according to the present invention may be a combination or hybrid of Fc fragments derived from IgG, IgA, IgD, IgE and IgM, that “combination” means a dimeric or multimeric polypeptide in which single-chain Fc fragments of the same origin are linked to a single-chain Fc fragment of a different origin to form a dimer or multimer [0060]. Kim teaches that native GLP-2 or its derivative and an immunoglobulin Fc fragment being covalently linked via a non-peptidyl polymer, wherein the native GLP-2 or its derivative has a thiol group introduced at its C-terminal end, and one end of the non-peptidyl polymer is linked to an amino acid residue of the GLP-2 (Abstract). It would have been obvious to modify Henriksen and administer the GLP-2 as a conjugate for prolonged in vivo half-life and an improved in vivo durability and stability (Abstract; claim 24; [0012-0014, 0026]).
Regarding claims 17-18, Kim teaches wherein the non-peptidyl polymer is selected from the group consisting of polyethylene glycol (claim 30). Kim further teaches that the non-peptidyl polymer suitable for the present invention has a molecular weight in the range from 1 to 100 kDa [0051]. It would have been obvious to modify Henriksen and administer the GLP-2 as a conjugate with PEG as the linker for prolonged in vivo half-life and an improved in vivo durability and stability (Abstract; claim 24; [0012-0014, 0026]).
Regarding claim 19, Kim further teaches derivatives such as CA GLP-2(A2G, 34C) [0027-0030, 0105, 0108], wherein the Histidine is modified to imidazoacethyldeshistidine, second amino acid (Alanine) is substituted with Glycine and the 34th amino acid is a Cysteine. Kim does not teach that the 34th amino acid is Lysine as recited in the instant SEQ ID NO: 4. However, Thim teaches GLP-2 variants with a K residue added in position 34 (Page130, line 15-16). Examiner notes that it would have been obvious to modify the GLP-2 peptide to include the teachings of Kim and Thim so as to arrive to the instant variant since both references teach specifically modifying the instant position 1, 2, 30 and 34 on the GLP-2 peptide and use the derivatives or variants to treat bone disorders such as osteoporosis.
Response to Arguments
Applicant’s arguments, see Applicant Arguments, filed 02/18/2026, with respect to the rejection(s) of claim(s) 1, 7-8, 10-19 under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Henriksen et al.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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/MERCY H SABILA/Examiner, Art Unit 1654