The Claim That Covers Orforglipron Chugai Keeps Its Broadest Compound Claim Alive as a Divisional

This application carries the broad compound claim of a long running Chugai family. Claim 1 is a single Markush formula, Formula (I), covering a pyrazolopyridine ring joined through a linker to an indole or pyrrolo[2,3-b]pyridine ring, together with any salt or solvate of such a compound. Thirteen claims follow that structure through to a pharmaceutical composition and to preventive or therapeutic agents for type 2 diabetes and obesity. One of the compounds falling inside Formula (I) is Example Compound 67, which is orforglipron, the oral GLP-1 receptor agonist Chugai licensed to Eli Lilly in 2018. AU 2026202208 is a divisional of AU 2024201884 and was published on the same day as its sibling AU 2026202206, which claims four named synthetic intermediates instead of the formula.

The Problem

The specification states the problem in one sentence at paragraph [0008]: provide a GLP-1 receptor agonist with the same effect as the GLP-1 peptide that can be administered non-invasively, with improved activity, metabolic stability and bioavailability.

The background explains why that matters. Glucagon-like peptide-1 is an incretin released from L cells in the small intestine when nutrients pass through the gut, and through its receptor it promotes glucose dependent insulin secretion, inhibits glucagon secretion, delays gastric emptying and suppresses feeding. GLP-1 analogues were already commercialised when the priority application was filed and the specification calls them among the most effective diabetes treatments available, on the strength of HbA1c reduction and weight loss. The catch, in the document’s own words, is that all of them require invasive subcutaneous administration.

Two workarounds are named. Patent Document 1, WO 2012/080471, covers improving oral bioavailability of the peptide semaglutide by pairing it with the absorption enhancer sodium N-(8-(2-hydroxybenzoyl)amino)caprylate, better known as SNAC. Patent Documents 2 and 3, WO 2009/111700 and WO 2010/114824, are earlier attempts at low molecular weight GLP-1 receptor agonists. The specification says of the small molecule work that further improvement is still required in activity, metabolic stability and bioavailability. It also notes two compounds already sitting in chemical libraries under the registry numbers RN 1638421-28-9 and RN 1269202-37-0, and a pyrazolopyridine from WO 2016/038045 aimed at sleeping sickness and leishmaniasis rather than diabetes. In other words, the ring system was not new. The claim rests on what is hung off it.

What This Invention Does

Claim 1 is a compound of Formula (I), a salt of it, or a solvate of either. The formula is a scaffold with sixteen lettered and numbered positions, and reading it in plain terms gives the shape of the molecule rather than a single structure.

X is either a nitrogen (-N=) or a carbon bearing hydrogen, halogen or C1-6 alkyl, and that single choice is what decides whether the left hand ring is an indole or a pyrrolo[2,3-b]pyridine. Y, the linker joining the two ring systems, is a carbonyl, a substituted methylene, or a sulfonyl. Q1 is a C6-10 aryl or a 5 to 10 membered heteroaryl carrying up to five substituents. Q2 is a 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl. R1 through R8 are hydrogen, halogen or small alkyl groups, with R7 and R8 allowed to close into a C3-15 cycloalkane ring. R9 is drawn as one of four sub-formulae, (IIa) to (IId), or else a carboxylic ester or a carboxamide. Z1 is one of five linker fragments, (IIIa) to (IIIe), binding the pyrazolopyridine to Z2, and Z2 is an alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group substituted from an eleven item list called Group A.

The dependent claims tighten each of those dials in turn. Claim 2 restricts Q1 to phenyl or pyridyl bearing one to four halogen or alkyl substituents. Claim 5 fixes Y as a carbonyl. Claim 6 makes R1 hydrogen, claim 7 sets both chain lengths n1 and n2 to zero, claim 8 fixes R9 as Formula (IIb), claim 9 limits X to -N=, -CH= or -CF=, and claim 10 fixes Z1 as Formula (IIIa). Follow that chain to the end and the claim has narrowed from a scaffold to something close to the shape of the lead compound.

Claims 11 to 13 are the use claims. Claim 11 is a pharmaceutical composition containing a Formula (I) compound, salt or solvate as active ingredient. Claim 12 is a preventive or therapeutic agent for a long list of indications: non-insulin-dependent diabetes, hyperglycaemia, impaired glucose tolerance, insulin dependent diabetes, diabetic complications, obesity, hypertension, hyperlipidaemia, arteriosclerosis, coronary heart disease, brain infarction, non-alcoholic steatohepatitis, Parkinson’s disease and dementia. Claim 13 narrows that to type 2 diabetes or obesity alone. Note what is absent: there is no method of treatment claim and no process claim anywhere in this divisional.

The numbers behind the claim are in the test examples. Potency was measured as cyclic AMP signalling in a human GLP1R stably expressing HEK293 line, with the response to human GLP-1 (7-37) at 1 nanomolar set as 100 per cent, and half maximal effective concentrations fitted by four parameter logistic regression. Table 3 lists an EC50 for Example Compounds 1 through 80. The strongest is Example 16 at 0.51 nM, followed by Example 31 at 0.74 nM and Example 26 at 0.77 nM. The weakest listed is Example 4 at 12 nM. Most of the table sits between 1 and 4 nM. Example Compound 67, the compound that went on to become orforglipron, is recorded at 1.2 nM.

Example Compound 67 is also the one carried into animal work. Infused continuously into anaesthetised cynomolgus monkeys to steady state plasma concentrations of 0.94, 1.6 and 4.8 nmol/L, then challenged with intravenous glucose at 0.5 g/kg, it raised the area under the insulin curve and lowered the area under the plasma glucose curve in a dose dependent way. The comparator, the injected peptide exenatide, produced a similar effect at steady state concentrations of 9.2 and 23.9 pmol/L. The specification then makes the comparison explicit: 9.2 pmol/L of exenatide is 38.5 pg/mL, close to the lower end of the 50 to 350 pg/mL therapeutic range quoted for exenatide in human diabetes patients, so Example Compound 67 is said to match exenatide from about 1.6 nmol/L upward.

Oral dosing in the same species suppressed food intake dose dependently over five consecutive days, with plasma concentrations immediately after the feeding measurement of 8.0 plus or minus 1.0 nM at 0.05 mg/kg and 16.3 plus or minus 2.3 nM at 0.1 mg/kg. The pharmacokinetics were run on a calcium salt hydrate crystal of Example Compound 67 at 0.05, 0.15, 0.45 and 1.35 mg/kg, two animals per dose. Time to peak concentration was 2.0 hours at every dose. Peak concentrations were 4.78, 20.7, 32.0 and 148 ng/mL and 24 hour exposures were 23.7, 135, 208 and 1040 ng.h/mL, so a 27 fold dose increase gave a 31 fold rise in peak and a 44 fold rise in exposure.

Key Features

• One formula, sixteen variable positions. Claim 1 defines the compound through X, Y, Q1, Q2, R1 to R9, n1, n2, Z1 and Z2, each with its own list of permitted values, so a single claim covers a large chemical space rather than one molecule.
• A ring choice written into a single atom. Setting X to nitrogen gives a pyrrolo[2,3-b]pyridine core and setting it to a substituted carbon gives an indole. Claim 9 narrows the choice to -N=, -CH= or -CF=.
• Acid replacements at R9. Rather than a free carboxylic acid, R9 is defined as one of four drawn sub-formulae or an ester or amide, which is how the family accommodates the oxadiazolone ring that the lead compounds actually carry.
• Composition and agent claims, no method claims. Claims 11 to 13 cover a pharmaceutical composition and preventive or therapeutic agents for fourteen named conditions, then narrow to type 2 diabetes and obesity. There is no method of treatment claim and no manufacturing claim in this divisional.
• Eighty measured potencies. Table 3 reports EC50 values for Example Compounds 1 to 80 against a human GLP1R cell line, ranging from 0.51 nM to 12 nM, which is the evidence the breadth of Formula (I) is asked to rest on.
• Primate data against an approved comparator. The insulin, glucose and food intake studies all run the test compound head to head with exenatide in cynomolgus monkeys and quote the plasma concentrations reached on both sides.

Who Is Behind It

The applicant is Chugai Pharmaceutical of Tokyo, majority owned by Roche since 2002 while remaining separately listed. The title page prints the name as Chugai Saiyaku Kabushiki Kaisha, which looks like a transcription slip: the company’s own English pages romanise it as Chugai Seiyaku Kabushiki Kaisha. Seventeen inventors are named, led by Hitoshi Yoshino. The Australian agent is Wrays Pty Ltd of Perth.

The commercially important fact about this family is not on the title page. Example Compound 67 is the compound Chugai developed as OWL833 and, on 27 September 2018, licensed worldwide to Eli Lilly for a 50 million dollar upfront payment plus milestones and royalties. Lilly developed it as LY3502970 and it is now known as orforglipron. Chugai continues to publish notices tracking Lilly’s announcements about the molecule, including one dated 2 April 2026.

The divisional position is set out fully at paragraph [0000], which is unusually helpful. This application is a divisional of AU 2024201884, filed 22 March 2024, itself a divisional of AU 2022205222, filed 13 July 2022, itself a divisional of AU 2020223687, filed 26 August 2020, itself a divisional of AU 2017330733, which entered the Australian national phase on 21 February 2019 from PCT/JP2017/034620, filed 26 September 2017 and published as WO 2018/056453. Priority is claimed from Japanese provisional application JP 2016-187605, filed 26 September 2016. That makes AU 2026202208 a fifth generation Australian filing on a ten year old priority date, and the priority country Japan.

Why It Matters

Small molecule GLP-1 agonists were, at the 2016 priority date, an unproven idea. Every marketed GLP-1 drug was a peptide requiring injection, and the only oral option in sight was a peptide paired with an absorption enhancer. A non-peptide that could be swallowed, and that held its own against exenatide in a primate at nanomolar plasma concentrations, was a genuinely different proposition. That is what the data tables in this specification set out to show.

The claim strategy is worth reading as its own object. The broad compound claim is the most valuable thing in a pharmaceutical family and also the most vulnerable, because breadth invites attack on sufficiency and inventive step. Filing a chain of divisionals keeps a claim of that breadth pending at the Australian office for as long as the parent stays alive, which matters when the compound inside the formula turns out to be a commercial product. This filing and its sibling AU 2026202206 divide the work: 2026202208 keeps the formula, 2026202206 keeps the manufacturing intermediates.

For readers trying to place the document, the useful frame is that this is not a new invention at all. The technical disclosure is identical to the 2017 PCT application, down to the same figures and the same example numbering, and nothing here can claim a later priority date. What is new is only the set of claims drawn around it.

Related Concepts

• Glucagon-like peptide-1 – the gut hormone whose receptor the claimed compounds are designed to switch on.
• GLP-1 receptor agonist – the drug class this family belongs to, historically all injected peptides.
• Orforglipron – the oral non-peptide agonist that corresponds to Example Compound 67 of this specification.
• Markush structure – the claim drafting device that lets one formula cover a family of molecules.
• EC50 – the half maximal effective concentration reported for each of the eighty example compounds.
• Type 2 diabetes – the lead indication named in claims 12 and 13.

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AU 2026202208 was published in the Australian Official Journal of Patents on 9 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.