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 .
DETAILED ACTION
Status of the Claims
Claims 1-20 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
Information Disclosure Statement
The references cited on the information disclosure statement(s) were considered and have been made of record to the extent that each was provided.
Claim Rejections - 35 USC § 112(b) or (pre-AIA ) 35 USC § 112 (2nd Par.)
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.
Claims 12-15 are 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 pre-AIA the applicant regards as the invention.
Claims 12 and 13 are indefinite because the claims depict a generalized or specific structure for how the insulin conjugate is constructed, however the claims do not provide a clear description of how or where the sugars are present in said conjugate, as required based on their dependency to claim 1.
Claim 14 and 15 are indefinite due to the recitation of a list of structure identifiers, without the correlating structures for said identifiers, which is considered an incorporation by reference, which renders the rejected claims incomplete. Where possible, claims are to be complete in themselves. Incorporation by reference "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience. See MPEP § 2173.05(s).
The Federal Circuit has noted that "the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiners demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation." Halliburton Energy Servs., 514 F.3d at 1255 (Fed. Cir. 2008).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 7-9, 16, 17, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by YAN (WO 2019/125878; Pub. Jun. 27, 2019; on IDS).
Yan discloses conjugate systems for insulin delivery where insulin is conjugated to two or more saccharides (title; abstract). Yan teaches compound ML-19 (p. 95) which is a linker for covalent conjugation to insulin. When conjugated to insulin at the N-hydroxysuccinimide (activated ester), the resulting compound is an insulin conjugate comprising a linker, wherein the linker is covalently linked to four saccharides (three mono saccharides, and one trisaccharide). Each of the four saccharides is carried on a ligand arm covalently linked to the linker near the distal end of the linker, which thus qualifies as a tetra-dentate linker according to the definition of this term at par. [0117] of the instant specification.
Regarding claims 2-3, Yan teaches saccharides including fucose, mannose, bimannose (i.e., dimannose), branched trimannose (bridging pgs. 13-14; p. 17) as well as aminoethylglucose, aminoethylmannose, aminoethylbimannose, aminoethyltrimannose, β-aminoethyl-N-acetylglucosamine, and aminoethylfucose (p. 27). Yan embodies branched trimannose in compound 6.
Regarding claim 4, Yan teaches conjugation of the saccharides at the A1 and B1 positions of insulin (compounds 1-26, pgs. 43-55).
Regarding claim 7, Yan teaches insulin lispro, insulin aspart, insulin glulisine, and insulin glargine (p. 25, lines 9-13).
Regarding claims 8-9, Yan teaches the insulin conjugates are responsive to saccharides such as glucose or alpha-methyl mannose (p. 66, lines 19-26; bridging pgs. 71-72).
Regarding claim 16, Yan teaches the use of carriers for delivery of the compounds (p. 69, lines 3-5).
Regarding claims 17 and 19, Yan teaches the treatment of diabetes (p. 69, lines 27-28).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 1-12 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over YAN (WO 2019/125878; Pub. Jun. 27, 2019; on IDS) in view of YANG (Yang, R., et al. JCI Insight (2018), 3(1); 1-14; on IDS) and FENG (WO 2018/175272; Pub. Sep. 27, 2018; on IDS).
The teachings of Yan are presented supra, and are incorporated herein. As detailed above, Yan teaches a compound comprising a tetra-dentate linker within the meaning of the instant claims. Yan’s teachings encompass tetra-dentate likers. For example, see the structure taught by Yan in general formula I, where n = 4. Yan further teaches compounds with one arm having a single terminal saccharide group (e.g., compounds 20-21, pgs. 52-53), two arms (at two separate locations on the insulin) having two terminal saccharide groups (e.g., compound 23, p. 54), three arms having 5 terminal saccharide groups (e.g., compounds 8-13, pgs. 46-49; compounds 16, p. 50), and compounds with 6 arms having 6 terminal saccharide groups (e.g., compound 13, p. 49; compound 17, p 51; p. 118, top). Thus, Yan teaches the concept of altering the number of linker arms to adjust the type and number of saccharide units conjugated to the insulin.
Similarly, Yang discloses mannosylated glucose-responsive insulin (GRI) analogs that can bind to the mannose receptor (MR) and to the insulin receptor (IR) (title; abstract). Yang teaches compounds GRI1, GRI2, and GRI3 (p. 3; Fig. 1). Each of these compounds are insulin conjugates comprising a linker, wherein the linker is covalently linked to multiple saccharides. GRI1 and GIR2 feature two terminal saccharide units (on two arms) GRI3 features three terminal saccharide units on three arms. Thus, Yang also teaches the concept of altering the number of arms to adjust the type and number of saccharide units conjugated to the insulin.
Feng discloses glucose responsive insulin compounds comprising tri-valent sugar clusters for the treatment of diabetes (title; abstract). Feng teaches the same sugar moieties as Yan (e.g., fucose, mannose, bimannose (i.e., dimannose), branched trimannose (p. 5, lines 6-8) as well as aminoethylglucose, aminoethylmannose, aminoethylbimannose, aminoethyltrimannose, β-aminoethyl-N-acetylglucosamine, and aminoethylfucose) (p. 5, lines 12-17). Feng teaches the conjugates are responsive to serum saccharides such as alpha-methyl mannose (p. 130, lines 21-28).
Thus, the teachings of the prior art establish an expectation of success using different numbers of linker arms to attach different types and numbers of saccharides to the insulin. Therefore, using a linker having four arms (e.g., as taught by Yan) would have been obvious to a skilled artisan in this field. Further, adding an additional linker arm to a tri-dentate linker (such as many of the compounds embodied by Yan, or those taught by Feng) amounts to the duplication of parts. The MPEP states that the mere duplication of parts has no patentable significance unless a new and unexpected result is produced. See MPEP § 2144.04(VI)(B). There is no evidence of new or unexpected results in this case.
Regarding claims 5-6, Yan teaches conjugation to 3, 4, or 5 or more separate ligands. Similarly, Feng teaches conjugation to at least three sugar clusters (p. 3, lines 20-23).
Regarding claims 10-11, Feng teaches the conjugate binds an endogenous saccharide binding molecule at a serum glucose concentration of 60 mg/dL or less when administered to a subject in need thereof. In particular embodiments, the endogenous saccharide binding molecule is human mannose receptor 1 (p. 6, lines 5-9).
Claim 12 is rejected as obvious over the structures taught by Yan (e.g., bridging pgs. 36-37) and Feng at p. 6 due to its indefiniteness and the high-level of generality with which it recites the chemical structures in the claim.
Regarding claims 18 and 20, Feng teaches treatment of type I diabetes, type II diabetes, or gestational diabetes (p. 13, lines 27-30).
Prior Art Not Relied Upon
The following prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
LIN (WO 2015051052): Lin discloses glucose responsive insulin compounds comprising bi-dentate linkers having sugar clusters for the treatment of diabetes.
Conclusion
Claims 1-20 are rejected. No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kevin S Orwig whose telephone number is (571)270-5869. The examiner can normally be reached Mon.-Fri. 7AM-4PM (with alternate Fridays off). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Engle can be reached Mon.-Fri. at (571)272-6660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Kevin S Orwig/
Primary Examiner, Art Unit 3991
Prosecution Insights