Patent: 10,258,639

Summary for Patent: 10,258,639

Title:	Methods for treating insulin resistance and for sensitizing patients to GLP1 agonist therapy
Abstract:	Methods for treatment of insulin resistance and type II diabetes by administration of inhibitors of the PKI pathway are provided. In some aspects, inhibitors of the PKI pathway, such as inhibitors of PIKB, HIF1 and/or mTOR, can be used to treat subject having insulin resistance who are refractory to GLP1 agonist therapy.
Inventor(s):	Montminy; Marc (La Jolla, CA), Van De Velde; Sam (La Jolla, CA), Blanchet; Emilie (La Jolla, CA)
Assignee:	Research Development Foundation (Carson City, NV)
Application Number:	15/308,652
Patent Claims:	see list of patent claims

United States Patent 10,258,639 (PKIB/mTOR/HIF Inhibition for GLP-1–Resistant Type 2 Diabetes): Claim Scope, Validity Risk, and US Patent Estate

Executive summary: US Patent 10,258,639 claims a US method of treating GLP-1 agonist–resistant diabetic subjects, using a PKIB pathway inhibitor selected from PKIB inhibition, mTOR inhibition, or HIF inhibition. The independent claim is broad at the therapeutic level (GLP-1–resistant diabetic subject) and broad at the inhibitor level (any inhibitor of PKIB, mTOR, or HIF), then narrows via dependent claims to Type 2 diabetes, resistance to specified GLP-1 drugs, human subjects, combination with a GLP-1 agonist, and further narrowing examples including sirolimus/everolimus/temsirolimus/rapamycin, and specific nucleic-acid complementarity/siRNA/dsRNA and named HIF inhibitors (including FG-4592, IOX2, 2-MeOE2, and others).

No actionable “comprehensive patent landscape” analysis can be produced without a complete, jurisdiction-linked dataset: the patent’s specification, prosecution history, publication counterparts, and the full US/WO/EP family plus litigation/OBR listings. Under the operating constraints, if that information is not fully available here, no complete and accurate landscape can be returned.

Therefore, the analysis below is limited strictly to claim construction and claim-critical design choices visible from the claim set provided, without asserting external estate details.

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What does US Patent 10,258,639 claim in plain US claim-scope terms?

Core invention (Claim 1):
A method for treating a diabetic subject resistant to GLP-1 agonist therapy by administering an “effective amount” of a PKIB pathway inhibitor, where the inhibitor is selected from:

1. an inhibitor of PKIB
2. an mTOR inhibitor
3. a HIF inhibitor

Key claim-scope drivers:

• Disease/responder phenotype is central: “diabetic subject resistant to a GLP1 agonist therapy.” This ties the method to a clinical selection criterion, not only to an active ingredient.
• Mechanism grouping is broad: “PKIB pathway inhibitor” is a functional umbrella that covers three mechanistic buckets (PKIB, mTOR, HIF).
• No dosage, route, or regimen is required in the independent claim (those can exist in the specification but are not in the claim text shown).
• Combination is optional at the independent claim level: Claim 1 does not require giving a GLP-1 agonist; Claim 5 makes that explicit.

Claim 1 is likely drafted to capture multiple compositions and regimens

The claim structure is a classic “platform method” approach:

• pick the patient class (GLP-1 resistance),
• pick the drug class under a mechanistic functional umbrella (PKIB/mTOR/HIF),
• provide “effective amount” without more.

That approach increases infringement risk for multiple competing candidates, but also creates validity and enforceability vulnerabilities around:

• the definition and measurement of “resistant,” and
• whether mTOR/HIF inhibitors are really “PKIB pathway inhibitors” in the required sense.

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How broad is the “PKIB pathway inhibitor” limitation and what are the infringement choke points?

Reading of the limitation:
Claim 1 requires that the administered agent is a “PKIB pathway inhibitor” and is “selected from” three categories: PKIB inhibitor, mTOR inhibitor, HIF inhibitor.

1) Category substitution risk (literal coverage is intentionally large)

Because Claim 1 lists alternative selections, an accused method using:

• an mTOR inhibitor for GLP-1–resistant diabetes, or
• a HIF inhibitor for GLP-1–resistant diabetes,
  can still meet the “PKIB pathway inhibitor” requirement if those drugs are within the ordinary meaning of “mTOR inhibitor” or “HIF inhibitor.”

2) Functional-meaning disputes are still possible

Even with category language, enforcement often turns on whether the accused agent is:

• an actual HIF pathway inhibitor (not just affecting hypoxia signaling downstream in an indirect way), or
• an actual mTOR inhibitor (not merely modulating mTOR-related transcription indirectly).

3) Patient selection is a real litigation choke point

Method claims that require treatment of a “resistant” phenotype can be avoided if the defendant:

• treats a broader population,
• or uses a different inclusion/exclusion criterion,
• or can’t practically demonstrate that the treated subject was “resistant” under the patent’s intended definition.

This becomes especially important because the claims shown do not specify the resistance testing method.

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What does the “GLP-1 agonist resistant” limitation likely mean for validity and enforceability?

The claim language is outcome-anchored to:

• “diabetic subject resistant to a GLP1 agonist therapy.”

Potential validity pressure points

If the specification does not provide:

• a clear operational definition of “resistant,” and
• a teaching that links PKIB/mTOR/HIF inhibition to GLP-1 resistance mechanistically and/or clinically,
  the claim can be attacked for:
• lack of enablement,
• indefiniteness (if “resistant” is not measurable with reasonable certainty),
• and/or lack of written description.

Potential enforceability pressure points

Even if the claim survives, proof at trial for method claims requires evidence that:

• the treated patient met the claimed resistance status,
• the accused therapy was given as part of the claimed method,
• and the claimed inhibitor is used as contemplated.

The resistance selection can be harder to prove in retrospective datasets than simple drug administration claims.

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Which dependent claims narrow the patient population and how do they change infringement risk?

Claim 2: diagnosed with Type II Diabetes

This narrows Claim 1 to Type 2 diabetes. If an accused program targets type 1 diabetes or another diabetic subgroup, Claim 2 avoids. But Claim 1 still may capture it if the subject is “diabetic” broadly and the defendant’s clinical category fits “diabetic subject.”

Claim 3: resistance to specific GLP-1 drugs

Claim 3 narrows to subjects resistant to:

• Exenatide,
• Liraglutide,
• Taspoglutide,
• Albiglutide,
• Lixisenatide.

This creates a “named list” dependency. For infringement of Claim 3, proof is needed that resistance includes one or more of these. If the accused method targets resistance to other GLP-1s (or to GLP-1RA class more generally without those named agents), Claim 3 may not be met, but Claim 1 and Claim 14 still might.

Claim 4: human subject

Claim 4 is a straightforward narrowing. If an accused method is preclinical or for non-human models, it avoids Claim 4.

Claim 14: resistance determined to GLP1 therapy

This tightens Claim 1 by adding an administrative/diagnostic predicate: resistance has been determined. It can shift the infringement proof burden to documentation of clinical assessment.

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How does the optional GLP-1 combination in Claim 5 affect design-around space?

Claim 5 adds: “further comprising administering to the subject a GLP1 agonist.”

Implications

• If a defendant uses only the PKIB/mTOR/HIF inhibitor without co-administering a GLP-1 agonist, it may avoid Claim 5 but still risk Claims 1, 2, 3, 4, 6-14 depending on what else is shown.
• If a defendant co-administers a GLP-1 agonist other than the named ones in Claim 15, Claim 5 can still be implicated.

Claim 15: GLP-1 agonist is one of five drugs

Claim 15 narrows the GLP-1 agonist selection to:

• Exenatide,
• Liraglutide,
• Taspoglutide,
• Albiglutide,
• Lixisenatide.

A design-around can attempt to select an alternative GLP-1 agonist; however, Claim 5 uses “GLP1 agonist” more generally, so avoiding only Claim 15 may not avoid the claim family.

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What is the technical meaning of Claims 6-11 (mTOR inhibitor and nucleic-acid PKIB inhibition)?

Claim 6: PKIB pathway inhibitor is an mTOR inhibitor

This is a category narrowing.

Claim 7: mTOR inhibitor examples

Lists:

• sirolimus,
• everolimus,
• temsirolimus,
• rapamycin.

This creates explicit coverage for these agents. For other mTOR inhibitors, Claim 6 could still be met if they are within ordinary meaning of “mTOR inhibitor” and the method otherwise meets Claim 1’s resistance predicate.

Claim 8-11: PKIB inhibition via inhibitory nucleic acids

• Claim 8: “inhibitor of PKIB”
• Claim 9: inhibitory nucleic acid
• Claim 10: nucleic acid is complementary to all or part of sequences corresponding to SEQ ID NO: 2, 4, 5, 6, 7, or 8
• Claim 11: nucleic acid is a siRNA or dsRNA

Where infringement can hinge

• Whether the accused nucleic acid is actually “complementary” to the claimed sequences,
• whether partial complementarity qualifies “all or part,”
• and whether the sequence overlap and strand structure meet “siRNA or dsRNA” requirements.

This cluster is likely the most “exact-match sensitive” part of the claim set. It is also where designing around by using different target sites or different RNA formats can be attempted.

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What is the meaning of Claims 12-13 (HIF inhibitors) and how do named compounds narrow coverage?

Claim 12: PKIB pathway inhibitor is a HIF inhibitor

Category narrowing.

Claim 13: named HIF inhibitors

Lists:

• FG-4592,
• IOX2,
• 2-Methoxyestradiol (2-MeOE2),
• CL67,
• CAY10585 (CAS 934593-90-5),
• sc-205346 (CAS 934593-90-5),
• Chetomin (CAS 1403-36-7),
• Chrysin (CAS 480-40-0).

Implications

• For these named agents, Claim 13 creates strong alignment between claimed subject matter and marketed or pipeline compounds.
• For other HIF inhibitors not named, Claim 12 can still be implicated if “HIF inhibitor” covers them.

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How strong is the claim set from a patentability and invalidity perspective (critically, claim-structure based)?

Because the only information provided is the claim set, strength can only be evaluated structurally.

1) Broad independent claim breadth increases both value and invalidity exposure

Claim 1’s breadth across:

• patient phenotype,
• and mechanism selection among three drug classes increases infringement reach. It also increases prior art and obviousness attack surfaces, because many combinations and mechanism-based diabetes rescue strategies exist historically.

2) Dependent claims with named agents can support specificity but can also cabin coverage

Claims 7 and 13 include named examples. These can:

• help show that the invention had defined embodiments,
• but they also make the claim set vulnerable if those specific examples are not supported in the specification or are known independently in the prior art.

3) Nucleic-acid complementarity claims can be both strong and fragile

Complementarity to specific SEQ IDs makes it easier to test infringement and validity against prior art sequences. But if the SEQ ID definitions are not tied to PKIB biology in the disclosure, the claim can be attacked on written description/enablement.

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What would a licensing or settlement posture likely target under this claim set?

The highest-value licensing targets generally track the broadest claim hooks:

• methods treating GLP-1–resistant diabetic subjects using mTOR or HIF inhibitors, and
• RNA-mediated PKIB inhibition using nucleic acids matching the SEQ IDs.

A potential license negotiation would likely focus on:

• whether a product’s clinical indication includes a “GLP-1 resistant” selection criterion,
• whether a combination regimen includes a GLP-1 agonist (Claim 5/15),
• and whether the product is classified as an mTOR/HIF inhibitor or as a direct PKIB inhibitor.

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Timeline and exclusivity: what can be concluded from the claim text alone?

No filing dates, patent term adjustments, PTA, pediatric exclusivity, terminal disclaimers, or FDA approval linkage are provided. Without those, no accurate exclusivity timeline can be generated.

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Orange Book status, Paragraph IV challenges, and FDA pathway: what can be concluded from the claim text alone?

The claim set alone does not establish whether:

• any active ingredient is FDA-approved,
• which NDA/BLA the patent is listed against in the Orange Book,
• whether any Paragraph IV notice exists,
• or whether the product is subject to 505(b)(2)/ANDA pathways.

No accurate regulatory-status conclusions can be produced here.

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Key Takeaways

• Claim 1 is the core: treat GLP-1 agonist–resistant diabetic subjects using a PKIB pathway inhibitor selected from PKIB inhibition, mTOR inhibition, or HIF inhibition.
• Claims 2-4 and 14 narrow patient class and resistance determination; these are likely decisive in infringement proof.
• Claims 5 and 15 create a combination hook with GLP-1 agonists, with dependent narrowing to named agents.
• Claims 6-7 focus on mTOR inhibitors and list sirolimus/everolimus/temsirolimus/rapamycin as examples.
• Claims 8-11 are the most sequence-sensitive: PKIB inhibitory nucleic acids complementary to specific SEQ IDs and formatted as siRNA/dsRNA.
• Claims 12-13 list multiple HIF inhibitors by name and CAS, creating high alignment with certain known small molecules.

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FAQs

1. Can a therapy avoid infringement by not co-administering a GLP-1 agonist?
   Avoiding Claim 5/15 may be possible, but Claim 1 can still be implicated because it does not require giving a GLP-1 agonist.

2. If a product treats “insufficient response” rather than “resistant,” does it avoid the patent?
   The claim text ties infringement to “resistant” status; whether “insufficient response” meets that term depends on the patent’s defined operational meaning in the specification.

3. Do unnamed mTOR inhibitors fall under the “mTOR inhibitor” limitation?
   Claim 6 does not limit to named mTOR inhibitors, so other mTOR inhibitors can still qualify if they meet ordinary meaning and the method otherwise meets Claim 1.

4. How design-around-proof is the siRNA/dsRNA claim language?
   It is highly testable because it is limited by nucleic-acid complementarity to specified SEQ IDs and by RNA format (siRNA/dsRNA), enabling target-site and sequence changes.

5. Would using a GLP-1 agonist outside the five named drugs avoid Claim 15?
   Yes for Claim 15 specifically, but Claim 5 only requires a GLP-1 agonist generally, so other claims may still be implicated.

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References (APA)

No external sources cited.

Details for Patent 10,258,639

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Glaxosmithkline Llc	TANZEUM	albiglutide	For Injection	125431	April 15, 2014	10,258,639	2035-05-06
Sanofi-aventis U.s. Llc	ADLYXIN	lixisenatide	Injection	208471	July 27, 2016	10,258,639	2035-05-06