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 .
Claim Status
The preliminary amendments filed 4/27/23 are acknowledged. Claims 1-16 are cancelled. New claims 17-33 are added. Claims 17-33 are currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statements filed on 1/11/23, 11/7/24, 4/9/25, 6/4/25, 9/17/25, 10/9/25, 12/11/25 have been considered. Signed copies are enclosed.
The references lined through were not considered because a full copy of the reference was not provided (see 37 CFR 1.98(a)).
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Further, the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
Abstract
The abstract of the disclosure is objected to because the term “GLP-1” is an acronym and/or abbreviation that should be spelled out upon first occurrence. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 17 is objected to because of the following informalities: the phrase “a glucagon-like peptide-1” should be amended to read “a glucagon-like peptide-1 (GLP-1)”. Appropriate correction is required.
Claim 17, 21, 31 and 32 are objected to because of the following informalities: the terms “Semaglutide” “Liraglutide”, “Exenatide”, “Lixisenatide”, “Albiglutide” and “Dulaglutide” are not proper names and should not be capitalized. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 18 and 24-26 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “normal” in claim 18 is a relative term which renders the claim indefinite. The term “normal” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The term “impaired” in claim 24 is a relative term which renders the claim indefinite. The term “impaired” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Regarding claim 25, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The term “hypersensitive ” in claim 26 is a relative term which renders the claim indefinite. The term “hypersensitive” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 17-20, 23, and 28 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tonneijck (hereinafter “Tonneijck I”, Diabetes Obes Metab. 2018 May ; 20(5): 1235–1245).
Instant claim 17 is directed to a method for treatment of hyperuricemia in a normoglycemic subject comprising administering a glucagon-like peptide-1 receptor agonist to a normoglycemic subject, said glucagon-like peptide-1 receptor agonist selected from the group consisting of Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide, Semaglutide, and combinations thereof.
Instant claim 18is directed to the method of claim 17, wherein the subject has a normal HbAic level.
Instant claim 19 is directed to the method of claim 17, wherein the subject has a fasting glucose level below 7.0 mmol/L.
Instant claim 20 is directed to the method of claim 18, wherein the subject has a HbAic level below 48 mmol/mol.
Instant claim 21 is directed to the method of claim 17, wherein the GLP-1 receptor agonist is Semaglutide or Liraglutide.
Instant claim 22 is directed to the method of claim 17, wherein the subject suffers from gout.
Instant claim 23 is directed to the method of claim 17, wherein the subject is overweight or obese.
Instant claim 24 is directed to the method of claim 17, wherein the subject has impaired kidney function or has osteoarthrosis.
Instant claim 25 is directed to the method of claim 17, wherein the subject is or has been treated with a xanthine oxidoreductase inhibitor (XOI), such as allopurinol.
Instant claim 26 is directed to the method of claim 25, wherein the subject is hypersensitive to XOI therapy or does not respond to XOI therapy.
Instant claim 27 is directed to the method of claim 25, wherein the XOI is allopurinol.
Instant claim 28 is directed to the method of claim 17, wherein the subject has a serum level of uric acid above 6 mg/dL prior to initiation of treatment.
Instant claim 29 is directed to the method of claim 17, wherein a uric acid level is reduced by at least 0.1 mg/dL over 8 weeks.
Instant claim 30 is directed to the method of claim 17, wherein the administering reduces joint pain, joint effusion, deposits of uric acid crystals, or deposition of uric acid in joints.
Instant claim 31 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is Liraglutide and a dosage is from 1 to 3 mg once per day.
Instant claim 32 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is Semaglutide and a dosage is from 0.25 to 5 mg weekly.
Instant claim 33 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is administered subcutaneously or orally.
Regarding the limitations of instant claim 17, Tonneijck teaches controlled clinical trials which assessed the actions of GLP-1RA-administraiton on kidney physiology (see e.g. abstract). The studies administered liraglutide or exenatide to patients (see e.g. abstract). The studies included subjects that were hyperuricemic (see abstract). Administration of the same drug (i.e. liraglutide or exenatide) to the same patient population (patients with hyperuricemia) would inherently result in the same treatment outcome.
Regarding the limitations of instant claims 18-20, the study population for study A in Tonneijck comprised hyperuricemic subjects (see e.g. page 5, under “Results”) that were treated with exenatide infusion (see abstract), and the subjects had HbA1c of 5.0-5.3 (see e.g. Table 1 on page 19). Applicant has not defined “Normal” and therefore the term was given the standard meaning in the art, which is that below 5.7% is considered “normal”. The fasting plasma glucose is 4.4-5.2 mmol/L, and the HbA1c is 31-34 (see e.g. Table 1 on page 19).
Regarding the limitations of instant claim 23, Tonneijck teaches that the subjects from Study A were overweight males (see e.g. abstract).
Regarding the limitations of instant claim 28, Tonneijck teaches that subjects from Study A had plasma uric acid at 6.33 mg/dL (see e.g. Table 1).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
1. Claim(s) 17-20, 23, and 28-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tonneijck (hereinafter “Tonneijck I”, Diabetes Obes Metab. 2018 May ; 20(5): 1235–1245. doi:10.1111/dom.13223) as evidenced by Tonneijck (hereinafter “Tonneijck II”, Diabetes Care. 2016 Nov;39(11):2042-2050. Epub 2016 Sep 1).
Instant claim 17 is directed to a method for treatment of hyperuricemia in a normoglycemic subject comprising administering a glucagon-like peptide-1 receptor agonist to a normoglycemic subject, said glucagon-like peptide-1 receptor agonist selected from the group consisting of Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide, Semaglutide, and combinations thereof.
Instant claim 18is directed to the method of claim 17, wherein the subject has a normal HbAic level.
Instant claim 19 is directed to the method of claim 17, wherein the subject has a fasting glucose level below 7.0 mmol/L.
Instant claim 20 is directed to the method of claim 18, wherein the subject has a HbAic level below 48 mmol/mol.
Instant claim 21 is directed to the method of claim 17, wherein the GLP-1 receptor agonist is Semaglutide or Liraglutide.
Instant claim 22 is directed to the method of claim 17, wherein the subject suffers from gout.
Instant claim 23 is directed to the method of claim 17, wherein the subject is overweight or obese.
Instant claim 24 is directed to the method of claim 17, wherein the subject has impaired kidney function or has osteoarthrosis.
Instant claim 25 is directed to the method of claim 17, wherein the subject is or has been treated with a xanthine oxidoreductase inhibitor (XOI), such as allopurinol.
Instant claim 26 is directed to the method of claim 25, wherein the subject is hypersensitive to XOI therapy or does not respond to XOI therapy.
Instant claim 27 is directed to the method of claim 25, wherein the XOI is allopurinol.
Instant claim 28 is directed to the method of claim 17, wherein the subject has a serum level of uric acid above 6 mg/dL prior to initiation of treatment.
Instant claim 29 is directed to the method of claim 17, wherein a uric acid level is reduced by at least 0.1 mg/dL over 8 weeks.
Instant claim 30 is directed to the method of claim 17, wherein the administering reduces joint pain, joint effusion, deposits of uric acid crystals, or deposition of uric acid in joints.
Instant claim 31 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is Liraglutide and a dosage is from 1 to 3 mg once per day.
Instant claim 32 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is Semaglutide and a dosage is from 0.25 to 5 mg weekly.
Instant claim 33 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is administered subcutaneously or orally.
Tonneijck I teaches controlled clinical trials which assessed the actions of GLP-1RA-administraiton on kidney physiology (see e.g. abstract). The studies administered liraglutide or exenatide to patients (see e.g. abstract). The studies included subjects that were hyperuricemic (see abstract). Administration of the same drug (i.e. liraglutide or exenatide) to the same patient population (patients with hyperuricemia) would inherently result in the same treatment outcome. Tonneijck I teaches that the study population for study A in Tonneijck I comprised hyperuricemic subjects (see e.g. page 5, under “Results”) that were treated with exenatide infusion (see abstract), and the subjects had HbA1c of 5.0-5.3 (see e.g. Table 1 on page 19). Applicant has not defined “Normal” and therefore the term was given the standard meaning in the art, which is that below 5.7% is considered “normal”. The fasting plasma glucose is 4.4-5.2 mmol/L, and the HbA1c is 31-34 (see e.g. Table 1 on page 19). Tonneijck I teaches that the subjects from Study A were overweight males (see e.g. abstract). Tonneijck I teaches that subjects from Study A had plasma uric acid at 6.33 mg/dL (see e.g. Table 1). Tonneijck I also teaches Study C, which administered liraglutide to individuals, including patients with hyperuricemia (see e.g. page 6-7). Treatment with Liraglutide reduced uric acid level by 0.12%, over 12 weeks (see e.g. abstract and Figure 2). As evidenced by Tonneijck II, which is the initial publication of the same study as described for Study C in Tonneijck I, the dosing for the liraglutide was 1.8 mg/day (see Tonneijck II, abstract). The administration of the liraglutide is subcutaneous (see Tonneijck II, right column). Tonneijck also teaches that semaglutide is another choice for GLP-1 agonist that, like liraglutide has similar long term therapeutic effects (see e.g. page 2).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the invention, to administer the liraglutide to normoglycemic individuals that have hyperuricemia because patients with hyperuricemia need treatment and Tonneijck showed that administration of liraglutide lowers uric acid levels in patients. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The instant specification teaches that hyperuricemia is a condition of high serum total urate levels, and uric acid is the final oxidation product of purine catabolism (see e.g. page 1). An individual having hyperuricemia is in need of uric acid reduction, and liraglutide has been demonstrated by Tonneijck to reduce uric acid levels upon administration. It would have been a known variation or principle in the art to apply a known treatment for a condition to all patients that suffer from the same condition (i.e. hyperuricemia). Furthermore the dosing set forth in Tonneijck II is a known dosing amount to achieve therapeutic benefit, and therefore would be a known principle in the art.
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the invention, to administer semaglutide as an alternative to liraglutide, because both compounds are GLP-1 agonists with the same target and similar modes of action. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if there was a recognized problem or need in the art, there was a finding that a finite number of identified, predictable solutions to the recognized problem were available, and one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success, the selection of one of the finite solutions would have been obvious to try. The problem for hyperuricemia is the lowering of uric acid to treat the patient. As shown by Tonneijck I, liraglutide, a GLP-1 agonist, was shown to decrease uric acid in the bloodstream. One of skill in the art would reasonably expect other agents that affect the same target, and which have a similar mechanism of action, to produce a similar result. There are a finite number of GLP-1 agonists available, and one of skill in the art could have reasonably pursued the administration of the other drugs in the same class to achieve similar effects of lowering uric acid. Furthermore, the semaglutide instead of liraglutide would amount to a simple substitution of agents known to target the same protein.
Furthermore, one of ordinary skilled in the art would have been motivated to optimize the dosing of the liraglutide to achieve the reduction in uric acid necessary to receive therapeutic benefit since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
2. Claim(s) 17-24, 28-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over W0 2012/100748 A1 (hereinafter “‘748 publication”; published 8/2/12; filed 1/29/12) in view of Tonneijck (hereinafter “Tonneijck I”, Diabetes Obes Metab. 2018 May ; 20(5): 1235–1245. doi:10.1111/dom.13223) as evidenced by Tonneijck (hereinafter “Tonneijck II”, Diabetes Care. 2016 Nov;39(11):2042-2050. Epub 2016 Sep 1).
Instant claim 17 is directed to a method for treatment of hyperuricemia in a normoglycemic subject comprising administering a glucagon-like peptide-1 receptor agonist to a normoglycemic subject, said glucagon-like peptide-1 receptor agonist selected from the group consisting of Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide, Semaglutide, and combinations thereof.
Instant claim 18is directed to the method of claim 17, wherein the subject has a normal HbAic level.
Instant claim 19 is directed to the method of claim 17, wherein the subject has a fasting glucose level below 7.0 mmol/L.
Instant claim 20 is directed to the method of claim 18, wherein the subject has a HbAic level below 48 mmol/mol.
Instant claim 21 is directed to the method of claim 17, wherein the GLP-1 receptor agonist is Semaglutide or Liraglutide.
Instant claim 22 is directed to the method of claim 17, wherein the subject suffers from gout.
Instant claim 23 is directed to the method of claim 17, wherein the subject is overweight or obese.
Instant claim 24 is directed to the method of claim 17, wherein the subject has impaired kidney function or has osteoarthrosis.
Instant claim 25 is directed to the method of claim 17, wherein the subject is or has been treated with a xanthine oxidoreductase inhibitor (XOI), such as allopurinol.
Instant claim 26 is directed to the method of claim 25, wherein the subject is hypersensitive to XOI therapy or does not respond to XOI therapy.
Instant claim 27 is directed to the method of claim 25, wherein the XOI is allopurinol.
Instant claim 28 is directed to the method of claim 17, wherein the subject has a serum level of uric acid above 6 mg/dL prior to initiation of treatment.
Instant claim 29 is directed to the method of claim 17, wherein a uric acid level is reduced by at least 0.1 mg/dL over 8 weeks.
Instant claim 30 is directed to the method of claim 17, wherein the administering reduces joint pain, joint effusion, deposits of uric acid crystals, or deposition of uric acid in joints.
Instant claim 31 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is Liraglutide and a dosage is from 1 to 3 mg once per day.
Instant claim 32 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is Semaglutide and a dosage is from 0.25 to 5 mg weekly.
Instant claim 33 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is administered subcutaneously or orally.
The ‘748 publication teaches treating a condition in a subject comprising activating a GLP-1 receptor comprising administering an effective amount of a GLP-1 receptor agonist (see e.g. claim 1). The method specifically treats pain (see e.g. claim 2). The pain can be osteoarthritis pain, gout pain, or other types of pain (see e.g. claim 4-5). The GLP-1 agonist can be liraglutide, exenatide or other agents (see e.g. claim 6).
The ‘748 publication does not describe treatment of a hyperuricemic patient that is normoglycemic, or that has the fasting glucose, HbA1c levels, or dosing regimens of the instant claims.
Tonneijck I teaches controlled clinical trials which assessed the actions of GLP-1RA-administraiton on kidney physiology (see e.g. abstract). The studies administered liraglutide or exenatide to patients (see e.g. abstract). The studies included subjects that were hyperuricemic (see abstract). Administration of the same drug (i.e. liraglutide or exenatide) to the same patient population (patients with hyperuricemia) would inherently result in the same treatment outcome. Tonneijck I teaches that the study population for study A in Tonneijck I comprised hyperuricemic subjects (see e.g. page 5, under “Results”) that were treated with exenatide infusion (see abstract), and the subjects had HbA1c of 5.0-5.3 (see e.g. Table 1 on page 19). Applicant has not defined “Normal” and therefore the term was given the standard meaning in the art, which is that below 5.7% is considered “normal”. The fasting plasma glucose is 4.4-5.2 mmol/L, and the HbA1c is 31-34 (see e.g. Table 1 on page 19). Tonneijck I teaches that the subjects from Study A were overweight males (see e.g. abstract). Tonneijck I teaches that subjects from Study A had plasma uric acid at 6.33 mg/dL (see e.g. Table 1). Tonneijck I also teaches Study C, which administered liraglutide to individuals, including patients with hyperuricemia (see e.g. page 6-7). Treatment with Liraglutide reduced uric acid level by 0.12%, over 12 weeks (see e.g. abstract and Figure 2). As evidenced by Tonneijck II, which is the initial publication of the same study as described for Study C in Tonneijck I, the dosing for the liraglutide was 1.8 mg/day (see Tonneijck II, abstract). The administration of the liraglutide is subcutaneous (see Tonneijck II, right column)
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the invention, to administer the liraglutide to normoglycemic individuals that have hyperuricemia because patients with hyperuricemia need treatment and Tonneijck showed that administration of liraglutide lowers uric acid levels in patients. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The instant specification teaches that hyperuricemia is a condition of high serum total urate levels, and uric acid is the final oxidation product of purine catabolism (see e.g. page 1). An individual having hyperuricemia is in need of uric acid reduction, and liraglutide has been demonstrated by Tonneijck to reduce uric acid levels upon administration. It would have been a known variation or principle in the art to apply a known treatment for a condition to all patients that suffer from the same condition (i.e. hyperuricemia). Furthermore the dosing set forth in Tonneijck II is a known dosing amount to achieve therapeutic benefit, and therefore would be a known principle in the art.
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the invention, to administer the liraglutide of Tonneijck to the patients of the ‘748 reference to treat pain in individuals suffering from hyperuricemia and other conditions such as gout or osteoarthritis pain. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The instant specification teaches that hyperuricemia is a condition of high serum total urate levels, and uric acid is the final oxidation product of purine catabolism (see e.g. page 1). The instant specification also defines gout as a condition created by buildup of monosodium urate or uric acid crystals on the articular cartilage of joints, tendons, and surrounding tissues due to elevated concentrations of total urate levels in the blood stream. An individual having gout and/or hyperuricemia is in need of uric acid reduction to address the cause of the condition, and liraglutide has been demonstrated by Tonneijck II to reduce uric acid levels upon administration. It would have been a known variation or principle in the art to apply liraglutide at the 1.8 mg dose that is known to lower uric acid levels in order to both treat hyperuricemia and simultaneously provide pain relief.
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the invention, to administer semaglutide as an alternative to liraglutide, because both compounds are GLP-1 agonists with the same target and similar modes of action. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if there was a recognized problem or need in the art, there was a finding that a finite number of identified, predictable solutions to the recognized problem were available, and one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success, the selection of one of the finite solutions would have been obvious to try. The problem for hyperuricemia is the lowering of uric acid to treat the patient. As shown by Tonneijck I, liraglutide, a GLP-1 agonist, was shown to decrease uric acid in the bloodstream. One of skill in the art would reasonably expect other agents that affect the same target, and which have a similar mechanism of action, to produce a similar result. There are a finite number of GLP-1 agonists available, and one of skill in the art could have reasonably pursued the administration of the other drugs in the same class to achieve similar effects of lowering uric acid. Furthermore, the semaglutide instead of liraglutide would amount to a simple substitution of agents known to target the same protein.
Furthermore, one of ordinary skilled in the art would have been motivated to optimize the dosing of the liraglutide to achieve the reduction in uric acid necessary to receive therapeutic benefit since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
3. Claim(s) 17-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tonneijck (hereinafter “Tonneijck I”, Diabetes Obes Metab. 2018 May ; 20(5): 1235–1245. doi:10.1111/dom.13223) as evidenced by Tonneijck (hereinafter “Tonneijck II”, Diabetes Care. 2016 Nov;39(11):2042-2050. Epub 2016 Sep 1) in view of Jacobson (downloaded from https://pharmacy.ucsf.edu/news/2015/07/study-discovers-why-leading-gout-medication-ineffective-many; published July 14, 2015).
Instant claim 17 is directed to a method for treatment of hyperuricemia in a normoglycemic subject comprising administering a glucagon-like peptide-1 receptor agonist to a normoglycemic subject, said glucagon-like peptide-1 receptor agonist selected from the group consisting of Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide, Semaglutide, and combinations thereof.
Instant claim 18is directed to the method of claim 17, wherein the subject has a normal HbAic level.
Instant claim 19 is directed to the method of claim 17, wherein the subject has a fasting glucose level below 7.0 mmol/L.
Instant claim 20 is directed to the method of claim 18, wherein the subject has a HbAic level below 48 mmol/mol.
Instant claim 21 is directed to the method of claim 17, wherein the GLP-1 receptor agonist is Semaglutide or Liraglutide.
Instant claim 22 is directed to the method of claim 17, wherein the subject suffers from gout.
Instant claim 23 is directed to the method of claim 17, wherein the subject is overweight or obese.
Instant claim 24 is directed to the method of claim 17, wherein the subject has impaired kidney function or has osteoarthrosis.
Instant claim 25 is directed to the method of claim 17, wherein the subject is or has been treated with a xanthine oxidoreductase inhibitor (XOI), such as allopurinol.
Instant claim 26 is directed to the method of claim 25, wherein the subject is hypersensitive to XOI therapy or does not respond to XOI therapy.
Instant claim 27 is directed to the method of claim 25, wherein the XOI is allopurinol.
Instant claim 28 is directed to the method of claim 17, wherein the subject has a serum level of uric acid above 6 mg/dL prior to initiation of treatment.
Instant claim 29 is directed to the method of claim 17, wherein a uric acid level is reduced by at least 0.1 mg/dL over 8 weeks.
Instant claim 30 is directed to the method of claim 17, wherein the administering reduces joint pain, joint effusion, deposits of uric acid crystals, or deposition of uric acid in joints.
Instant claim 31 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is Liraglutide and a dosage is from 1 to 3 mg once per day.
Instant claim 32 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is Semaglutide and a dosage is from 0.25 to 5 mg weekly.
Instant claim 33 is directed to the method of claim 17, wherein the glucagon-like peptide-1 receptor agonist is administered subcutaneously or orally.
Tonneijck I teaches controlled clinical trials which assessed the actions of GLP-1RA-administraiton on kidney physiology (see e.g. abstract). The studies administered liraglutide or exenatide to patients (see e.g. abstract). The studies included subjects that were hyperuricemic (see abstract). Administration of the same drug (i.e. liraglutide or exenatide) to the same patient population (patients with hyperuricemia) would inherently result in the same treatment outcome. Tonneijck I teaches that the study population for study A in Tonneijck I comprised hyperuricemic subjects (see e.g. page 5, under “Results”) that were treated with exenatide infusion (see abstract), and the subjects had HbA1c of 5.0-5.3 (see e.g. Table 1 on page 19). Applicant has not defined “Normal” and therefore the term was given the standard meaning in the art, which is that below 5.7% is considered “normal”. The fasting plasma glucose is 4.4-5.2 mmol/L, and the HbA1c is 31-34 (see e.g. Table 1 on page 19). Tonneijck I teaches that the subjects from Study A were overweight males (see e.g. abstract). Tonneijck I teaches that subjects from Study A had plasma uric acid at 6.33 mg/dL (see e.g. Table 1). Tonneijck I also teaches Study C, which administered liraglutide to individuals, including patients with hyperuricemia (see e.g. page 6-7). Treatment with Liraglutide reduced uric acid level by 0.12%, over 12 weeks (see e.g. abstract and Figure 2). As evidenced by Tonneijck II, which is the initial publication of the same study as described for Study C in Tonneijck I, the dosing for the liraglutide was 1.8 mg/day (see Tonneijck II, abstract). The administration of the liraglutide is subcutaneous (see Tonneijck II, right column). Tonneijck also teaches that semaglutide is another choice for GLP-1 agonist that, like liraglutide has similar long term therapeutic effects (see e.g. page 2).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the invention, to administer the liraglutide to normoglycemic individuals that have hyperuricemia because patients with hyperuricemia need treatment and Tonneijck showed that administration of liraglutide lowers uric acid levels in patients. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The instant specification teaches that hyperuricemia is a condition of high serum total urate levels, and uric acid is the final oxidation product of purine catabolism (see e.g. page 1). An individual having hyperuricemia is in need of uric acid reduction, and liraglutide has been demonstrated by Tonneijck to reduce uric acid levels upon administration. It would have been a known variation or principle in the art to apply a known treatment for a condition to all patients that suffer from the same condition (i.e. hyperuricemia). Furthermore the dosing set forth in Tonneijck II is a known dosing amount to achieve therapeutic benefit, and therefore would be a known principle in the art.
Tonneijck does not teach administration of allopurinol, or altered sensitivity to allopurinol.
Jacobson teaches that allopurinol is the first choice medication for treating gout (see e.g. page 2). Allopurinol efficacy is altered based on a specific drug transporter (see e.g. page 2). Patients that respond differently to the drug could ultimately need newer medications that would be more effective (see e.g. page 3).
It would have been obvious to combine treatment with GLP-1 agonists and allopurinol for treatment of hyperuricemia and gout, which results from hyperuricemia, because both are known to decrease uric acid in the bloodstream, and therefore GLP-1 agonists would be especially helpful when attempting to increase treatment success for patients that do not respond to allopurinol. One would have been motivated to do so because each of the therapies have been individually taught in the prior art to be successful in treating hyperuricemic conditions. This situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering a GLP-1 agonist in combination with allopurinol as taught in Tonneijck, in view of the teachings of Jacobson, one would achieve a method for treating hyperuricemia and gout, especially in situations where the subject does not initially respond to allopurinol.
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the invention, to administer semaglutide as an alternative to liraglutide, because both compounds are GLP-1 agonists with the same target and similar modes of action. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if there was a recognized problem or need in the art, there was a finding that a finite number of identified, predictable solutions to the recognized problem were available, and one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success, the selection of one of the finite solutions would have been obvious to try. The problem for hyperuricemia is the lowering of uric acid to treat the patient. As shown by Tonneijck I, liraglutide, a GLP-1 agonist, was shown to decrease uric acid in the bloodstream. One of skill in the art would reasonably expect other agents that affect the same target, and which have a similar mechanism of action, to produce a similar result. There are a finite number of GLP-1 agonists available, and one of skill in the art could have reasonably pursued the administration of the other drugs in this class to achieve similar effects of lowering uric acid. Furthermore, the semaglutide instead of liraglutide would amount to a simple substitution of agents known to target the same protein.
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the invention, to administer semaglutide as an alternative to liraglutide, because both compounds are GLP-1 agonists with the same target and similar modes of action. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if there was a recognized problem or need in the art, there was a finding that a finite number of identified, predictable solutions to the recognized problem were available, and one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success, the selection of one of the finite solutions would have been obvious to try. The problem for hyperuricemia is the lowering of uric acid to treat the patient. As shown by Tonneijck I, liraglutide, a GLP-1 agonist, was shown to decrease uric acid in the bloodstream. One of skill in the art would reasonably expect other agents that affect the same target, and which have a similar mechanism of action, to produce a similar result. There are a finite number of GLP-1 agonists available, and one of skill in the art could have reasonably pursued the administration of the other drugs in the same class to achieve similar effects of lowering uric acid. Furthermore, the semaglutide instead of liraglutide would amount to a simple substitution of agents known to target the same protein.
Furthermore, one of ordinary skilled in the art would have been motivated to optimize the dosing of the liraglutide to achieve the reduction in uric acid necessary to receive therapeutic benefit since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
Conclusion
No claim is allowed.
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/ANDREA K MCCOLLUM/Examiner, Art Unit 1674