Patent: 10,092,542

Summary for Patent: 10,092,542

Title:	Methods of using (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoi- soindoline-1,3-dione
Abstract:	Stereomerically pure (+)-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoiso- indoline-1,3-dione, substantially free of its (-) isomer, and prodrugs, metabolites, polymorphs, salts, solvates, hydrates, and clathrates thereof are discussed. Also discussed are methods of using and pharmaceutical compositions comprising the (+) enantiomer of 2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoin- doline-1,3-dione are disclosed. The methods include methods of treating and/or preventing disorders ameliorated by the reduction of levels of TNF-.alpha. or the inhibition of PDE4.
Inventor(s):	Muller; George W. (Rancho Santa Fe, CA), Schafer; Peter H. (Belle Mead, NJ), Man; Hon-Wah (Princeton, NJ), Ge; Chuansheng (Belle Mead, NJ)
Assignee:	Celgene Corporation (Summit, NJ)
Application Number:	15/629,678
Patent Claims:	see list of patent claims

United States Patent 10,092,542 Claims and US Patent Landscape for (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-4-acetylamino-isoindolin-1,3-dione (Bone Loss)

Executive summary: US Patent 10,092,542 claims a method of treating/managing bone loss in a patient by administering (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-4-acetylamino-isoindolin-1,3-dione (a specific chiral, small-molecule chemical entity) and pharmaceutically acceptable salts, with claim coverage that is broad on bone-loss etiology (primary and secondary), disease subclasses (type 1/type 2 osteoporosis and multiple secondary causes), and combination regimens (bisphosphonates, teriparatide, strontium ranelate, raloxifene, denosumab, calcium/vitamin D/K). From a patent-clearing standpoint, the estate’s practical infringement risk concentrates on therapeutic use and combination therapy rather than formulation or manufacturing, because the claims are written as medical-use method claims whose scope turns on (i) patient bone-loss indication and (ii) whether the administered active is the claimed (+) enantiomer and/or acceptable salt, and (iii) whether the regimen includes the enumerated combination agents.

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What is US Patent 10,092,542 actually claiming for bone loss treatment?

Short answer: The patent claims a method of treating or managing bone loss by administering a therapeutically effective amount of the specific (+)-enantiomer chemical (or a salt). Dependent claims expand the covered patient populations and regimen structures: primary osteoporosis (type 1 or type 2), secondary bone loss tied to specified underlying disorders, bone-loss caused by therapeutic agents with specified example classes, and combination/alternation with listed osteoporosis agents and supplements.

Core claim 1 scope (independent claim)

Claim 1: A method of treating/managing bone loss comprising administering a therapeutically effective amount of:

• (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-4-acetylamino-isoindolin-1,3-dione
  or a pharmaceutically acceptable salt.

Interpretive levers that define scope

1. Active identity constraint: The method requires the specific chiral (+) compound or its salt.
2. Molecule-to-indication bridge: Bone loss is the treated condition, not necessarily osteoporosis only.
3. No route/formulation limitations in the claim excerpt: As provided, claim 1 does not lock route (oral/injectable) or dosage form, which in practice can broaden infringement coverage to any delivery mode as long as the patient receives the active in vivo.

Dependent claim set expands indication breadth

• Claim 2: bone loss is primary.

• Claim 3/4: primary type 1 osteoporosis or primary type 2 osteoporosis.

• Claim 5–10: bone loss is secondary due to specified underlying disorders:

  • Autoimmune/inflammatory: rheumatoid arthritis; lupus; ankylosing spondylitis; (also multiple sclerosis appears twice)
  • Neurologic: Parkinson’s disease; spinal cord injury
  • GI disorders: celiac disease; inflammatory bowel disease
  • Endocrine/metabolic: diabetes; hyperparathyroidism; hyperthyroidism; Cushing’s syndrome; thyrotoxicosis; premature menopause; unusual testosterone levels
  • Hematologic: leukemia; lymphoma; multiple myeloma; sickle cell disease; blood and bone marrow disorder; thalassemia
  • Oncology: bone cancer; breast cancer; prostate cancer
  • Mental illness: depression; eating disorder

• Claim 11–14: bone loss caused by a therapeutic agent, example therapeutic-agent classes:

  • Corticosteroids: prednisone or dexamethasone
  • Antiepileptics: barbiturates or phenytoin

• Claim 12 includes other example therapeutic agents (expanded list):

  • L-thyroxine; aromatase inhibitor; methotrexate; depot-progesterone; GnRH agonist; proton pump inhibitor; thiazolidinedione; lithium.

• Claim 15: bone-loss disorders expressly listed as targets:

  • osteogenesis imperfecta; osteomalacia; rickets; ostesis fibrosa cystic; Paget’s disease.

Combination/alternation claim (claim 16–17) is a major infringement vector

• Claim 16: method of claim 1 where the active is administered in combination or alternation with one or more additional active agents.
• Claim 17: additional active agents include:
  • bisphosphonate; teriparatide; strontium renelate; raloxifene; denosumab; calcium; vitamin D; vitamin K (or combinations).

Why this matters legally and commercially

• Combination therapy claims are often the fastest way to capture real-world regimens, because bone-loss care frequently involves stacking antiresorptives/osteogenesis stimulators plus calcium/vitamin D.
• If the claimed (+) compound is used alongside an approved osteoporosis agent, the regimen may fall inside claim 16–17 even if each component individually has its own patent estate.

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Which claim elements are most likely to be challenged for invalidity or design-around?

Short answer: Likely attack surfaces are (i) indefiniteness/antecedent basis and claim clarity around the chemical structure shown in the excerpt, (ii) enablement/utility for the wide indication sweep across primary, secondary causes, and agent-induced bone loss, and (iii) written description for the broad dependent claim enumerations, especially where mechanistic support may be limited.

Chemical specificity and enantiomer issues

The claims are limited to the (+)-enantiomer. That typically narrows the patent compared with racemic or non-stereospecific species, but it also creates:

• A potential litigation issue if accused products do not deliver the same stereochemical composition.
• A potential chemistry burden for the patentee to show operability across the claimed salt forms and dosing.

Breadth of disease and etiology coverage

Claims list many underlying conditions (autoimmune, endocrine, hematologic, oncology, GI, mental illness) and agent-induced bone loss classes (corticosteroids, antiepileptics, others). The wider the indication net, the more pressure on:

• the disclosure’s support for treating each category, and
• whether the mechanism is general (bone metabolism broadly) or specific (one pathophysiology).

Combination claim dependence

Claim 16 makes infringement easier to establish in real-world combination settings, but it can also create design-around paths:

• Avoid one or more named additional actives if the list is treated as closed (depending on claim construction and whether “additional active agents” is limited to enumerated examples).
• Alter regimen structure (sequence/timing) only if claim construction requires “combination or alternation” in a particular temporal overlap.

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What patent landscape typically surrounds US 10,092,542 in the US?

Short answer: Without the patent’s publication history, assignee, priority chain, and related family members, a complete US landscape cannot be constructed from the claims excerpt alone. Still, for business planning, the landscape structure for medical-use small-molecule bone-loss claims is typically organized into four buckets:

1. Active ingredient patents (composition of matter for the specific stereoisomer and salts),
2. Medical-use patents (methods like claims 1–17),
3. Formulation patents (dosage form, controlled release, excipients, etc.),
4. Combination/regimen patents (pairing with bisphosphonates, denosumab, teriparatide, etc.).

This patent excerpt is drafted as method-of-use, so the most relevant adjacent competitor patents are those that either:

• claim the same (+) compound for bone indications, and/or
• claim dosing regimens with overlapping combination partners.

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How does the claim structure affect design-around strategies for competitors?

Short answer: The combination of a stereochemically specific active and broad medical-use language creates two primary design-around axes: (i) avoid administering the claimed (+) enantiomer (or its salts), or (ii) avoid using it to treat the covered bone-loss categories in combination/alternation with the enumerated actives.

1) Stereochemical design-around

• Switching to a different stereoisomer or racemate can fall outside the claim if the claim construction strictly limits “(+)-” identity.
• This is also where enforcement often becomes chemistry-intensive: proof may require stereospecific analysis of drug substance in the accused product.

2) Indication/claim-purpose design-around

• Because claim 1 is “method of treating or managing bone loss,” off-label or non-bone-loss indications likely do not avoid infringement if the method is still a bone-loss treatment in practice.
• The dependent claims enumerate secondary causes. If the target population is not within those examples, a defendant may argue narrower coverage under claim construction (but claim 1 can still capture bone loss generally).

3) Combination/regimen design-around

• If a competitor uses the claimed compound but avoids combination with named actives, they may attempt to avoid claim 16–17.
• If claim 16 is construed broadly as “combination or alternation” including any co-administration, then regimen separation may still be insufficient if the therapeutic effect is pursued.

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What would a licensing or FTO position look like for US method claims like this?

Short answer: For a new entrant planning US launch of a bone-loss product containing the same (+) active, the practical risk is highest if:

• the product is intended and marketed for osteoporosis or bone-loss categories, and
• it uses the agent in conjunction with commonly used osteoporosis therapies (bisphosphonates, denosumab, teriparatide, raloxifene, plus calcium/vitamin D/K).

Operationally, an FTO approach would treat this patent as a medical-use “usage moat,” meaning the key questions are less about manufacturing and more about:

• label indications and physician communication,
• clinical trial protocols,
• co-therapy instructions, and
• whether the product is sold as an adjunct to standard-of-care osteoporosis regimens.

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When does exclusivity end and when can generics/biosimilars launch?

Short answer: This cannot be determined from the claims excerpt. Exclusivity in the US depends on the Orange Book listing (NDA/BLA linkage), patent term (including patent term adjustment), and any regulatory exclusivity (3 years/5 years/7.5 years for biologics where applicable, pediatric, etc.). A complete exclusivity timeline requires the patent’s filing and issue data, family details, and any FDA-linked registrations.

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What Paragraph IV / biosimilar challenges are implicated?

Short answer: The claims excerpt does not provide whether US 10,092,542 is listed in the Orange Book for an NDA, or whether there has been any litigation (ANDA Paragraph IV) or BLA-related biosimilar challenge. Without case captions, FDA application numbers, and Orange Book listings, a definitive litigation landscape cannot be produced.

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Key Takeaways

• US 10,092,542 claims a medical method for treating/managing bone loss using a specific stereochemically defined (+) small-molecule (or pharmaceutically acceptable salts).
• Dependent claims expand coverage across:
  • primary osteoporosis (type 1 and type 2),
  • secondary bone loss caused by a wide list of underlying disorders (autoimmune, GI, endocrine, hematologic, oncology, neurologic, mental illness),
  • bone loss induced by therapeutic agents (examples include corticosteroids and several other drug classes),
  • specified bone-loss disorders (osteogenesis imperfecta, osteomalacia, rickets, cystic fibrous osteitis, Paget’s disease),
  • and combination/alternation with osteoporosis standard-of-care and supplement agents (bisphosphonates, teriparatide, strontium ranelate, raloxifene, denosumab, calcium/vitamin D/vitamin K).
• The most commercially salient infringement risk is real-world use in osteoporosis practice because combination therapies with the listed agents are common.
• A complete US “critical landscape” (Orange Book status, expiration timelines, competing patents, litigation, settlements) cannot be derived from the claims excerpt alone.

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FAQs

1. Does US 10,092,542 cover racemic versions or only the (+)-enantiomer?
2. Would co-administration with calcium and vitamin D alone trigger claim 17?
3. If a product is intended for non-osteoporosis bone conditions, is it still covered by claim 1’s “bone loss” framing?
4. How are “combination or alternation” regimens typically construed in US medical-use patents?
5. What types of evidence are used to prove stereoisomer infringement for (+) enantiomer drug products in US litigation?

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References

1. US Patent 10,092,542 (claims provided in prompt).

Details for Patent 10,092,542

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen Inc.	PROLIA	denosumab	Injection	125320	June 01, 2010	10,092,542	2037-06-21
Amgen Inc.	XGEVA	denosumab	Injection	125320	November 18, 2010	10,092,542	2037-06-21