Details for Patent: 10,793,596

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Which drugs does patent 10,793,596 protect, and when does it expire?

Patent 10,793,596 protects KORSUVA and is included in one NDA.

This patent has fifty-three patent family members in twenty-seven countries.

Summary for Patent: 10,793,596

Title:	Synthetic peptide amides
Abstract:	The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: These compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.
Inventor(s):	Claudio D. Schteingart, Frédérique Menzaghi, Guangcheng Jiang, Roberta Vezza Alexander, Javier Sueiras-Diaz, Robert H. Spencer, Derek T. Chalmers, Robert Zhiyong Luo
Assignee:	Vifor Fresenius Medical Care Renal Pharma Ltd
Application Number:	US16/199,308
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,793,596
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

US Patent 10,793,596: Difelikefalin Claims, Exclusivity, Litigation and Patent Landscape

US Patent 10,793,596 protects difelikefalin, the synthetic kappa opioid receptor agonist marketed as Korsuva. Its claims cover the active peptide, selected hydrochloride and acetate forms, solid and lyophilized compositions, aqueous injectable formulations, and treatment of pruritus associated with chronic kidney disease, liver disease, atopic dermatitis, contact dermatitis, and psoriasis. The patent’s principal commercial importance is its method-of-use coverage for chronic kidney disease-associated pruritus in hemodialysis patients.

What drug does US Patent 10,793,596 protect?

The patent protects difelikefalin, also known by its development code CR845. The claimed peptide is:

D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)]-OH

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist. Cara Therapeutics developed the drug, and Vifor Pharma became its commercial partner for the dialysis market. The FDA approved Korsuva injection on August 23, 2021, for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis.[1]

Item	Detail
Active ingredient	Difelikefalin
Development code	CR845
Brand	Korsuva
Drug class	Selective kappa opioid receptor agonist
Dosage form	Intravenous injection
FDA approval	August 23, 2021
Approved indication	CKD-associated pruritus in adults undergoing hemodialysis
Patent analyzed	US 10,793,596
Patent owner/assignee history	Cara Therapeutics-related entities
Earliest priority date generally associated with this family	November 25, 2013
Projected nominal patent expiration	November 25, 2034

The patent is materially broader than the original FDA label because its method claims cover several pruritus etiologies that were not part of the initial US approval.

What claims are covered by US Patent 10,793,596?

US 10,793,596 contains three practical claim groups: compound claims, composition claims, and therapeutic method claims.

Which difelikefalin chemical forms are claimed?

Claim 1 covers the difelikefalin peptide and any pharmaceutically acceptable salt, hydrate, or acid salt hydrate. Claims 2 and 3 expressly identify hydrochloride and acetate forms.

This creates a broad chemical perimeter around the active pharmaceutical ingredient:

Claim	Protected subject matter
1	Difelikefalin and pharmaceutically acceptable salts, hydrates, and acid salt hydrates
2	Difelikefalin hydrochloride forms
3	Difelikefalin acetate forms
4	Solid compositions containing the claimed compound
5	Lyophilized solid compositions

The wording reaches the compound itself rather than only a particular commercial formulation. A generic or competing product containing the same difelikefalin molecular entity would face a direct composition-claim issue even if it used a different excipient system, vial configuration, or manufacturing process.

The salt coverage is important because an applicant cannot necessarily avoid claim 1 by selecting a different counterion. Claim 1 covers pharmaceutically acceptable salts generally, while claims 2 and 3 provide expressly recited hydrochloride and acetate embodiments.

What formulations are protected by the patent?

Claims 6 through 9 cover pharmaceutical compositions and aqueous solutions containing difelikefalin. The claims specifically include isotonic and buffered solutions.

Claim	Formulation scope
6	Pharmaceutical composition with difelikefalin and an excipient or carrier
7	Aqueous solution
8	Isotonic aqueous solution
9	Buffered aqueous solution

These claims are relevant to injectable products because Korsuva is supplied as an intravenous injection. The claims do not appear limited to a particular concentration, dose, pH, buffer species, container, preservative, or administration device based on the claim language supplied.

A competing formulation could still face claim 6 if it contains difelikefalin and a pharmaceutical excipient or carrier. Claims 7 through 9 narrow the formulation category but remain commercially significant for parenteral products.

What pruritus indications are covered?

Claims 10 through 18 cover treatment of pruritus associated with specified diseases and conditions.

Claim	Disease or patient population
10	Kappa opioid receptor-associated pruritus
11	Chronic kidney disease-associated pruritus
12	CKD-associated pruritus in a hemodialysis patient
13	End-stage renal disease-associated pruritus
14	Pruritus associated with primary biliary cholangitis, primary biliary cirrhosis, or chronic cholestatic liver disease
15	Pruritus associated with chronic cholestatic liver disease
16	Atopic dermatitis-associated pruritus
17	Contact dermatitis-associated pruritus
18	Psoriasis-associated pruritus

Claim 12 is the most commercially important method claim because it closely tracks the approved Korsuva market: adults with CKD-associated pruritus undergoing hemodialysis. Claim 13 separately targets end-stage renal disease. Claims 14 through 18 extend the patent’s method coverage into non-dialysis and dermatologic populations.

When does US Patent 10,793,596 lose exclusivity?

The nominal expiration date is November 25, 2034, based on the family’s November 25, 2013 priority date and the standard 20-year patent term framework.[2] The enforceable expiration date should be confirmed against the USPTO patent-term-adjustment calculation and any terminal disclaimer recorded in the file history.

The patent does not provide regulatory exclusivity by itself. Korsuva received five-year new chemical entity exclusivity from the FDA, subject to the applicable Hatch-Waxman framework. That exclusivity period began with approval in August 2021 and generally blocked submission of an ANDA containing a Paragraph IV certification until August 2026, absent a statutory exception.[3]

Exclusivity protection	Approximate end
FDA five-year NCE exclusivity	August 2026
US Patent 10,793,596 nominal expiration	November 25, 2034
Potential pediatric extension	Not established from the supplied record

The patent therefore extends well beyond the FDA’s initial NCE exclusivity period. After NCE exclusivity ends, an ANDA applicant may file a patent certification, but commercial launch depends on the certifications, litigation, statutory stay, settlement terms, and any other unexpired Orange Book patents.

What is the Orange Book status of difelikefalin and Korsuva?

The FDA Orange Book is the controlling source for determining which patents are listed against an approved small-molecule drug product and which use codes apply.[4] US Patent 10,793,596 is the principal patent associated with the claimed difelikefalin compound and pruritus uses.

The patent’s relevance to an ANDA depends on how it is listed:

• A compound or formulation listing can support a Paragraph IV challenge directed to the product.
• A method-of-use listing can require a section viii “carve-out” if the ANDA omits the patented indication.
• If the ANDA label retains the patented CKD-hemodialysis pruritus indication, the applicant would generally need to address the listed use patent through a certification.
• A label carve-out may be commercially unattractive because CKD-associated pruritus in hemodialysis is the core Korsuva market.

A generic applicant seeking approval only for an unpatented indication could attempt a section viii strategy. That path is less useful where the approved label, prescribing information, or expected commercial use would still encourage use for the patented dialysis population.

Which companies are challenging difelikefalin patents?

No publicly established Paragraph IV litigation outcome or settlement involving US 10,793,596 is identified in the supplied materials. The patent’s commercial challengers would most likely be generic injectable manufacturers with peptide synthesis, sterile fill-finish, and dialysis-channel capabilities.

Potential challenger categories include:

1. Large generic injectable companies filing an ANDA for difelikefalin injection.
2. Contract manufacturers partnering with a specialty pharmaceutical company.
3. Dialysis-focused companies seeking vertical integration or lower drug-acquisition costs.
4. International manufacturers using a US ANDA route after NCE exclusivity expires.

The strongest invalidity targets would likely involve written description, enablement, obviousness, claim construction, and the scope of the salt and formulation language. The method claims may be attacked through indication carve-outs or by arguing that the proposed labeling does not encourage the patented use.

How strong is the patent estate for difelikefalin?

US Patent 10,793,596 is strong against a product that contains difelikefalin because claim 1 directly covers the active peptide and broad categories of pharmaceutically acceptable salts and hydrates. The patent is weaker against a genuinely different kappa agonist because the claims are compound-specific rather than class-based.

Strengths

• Direct composition coverage of difelikefalin.
• Express salt, hydrate, hydrochloride, and acetate coverage.
• Solid and lyophilized composition protection.
• Aqueous, isotonic, and buffered solution claims.
• Method claims aligned with the commercial dialysis indication.
• Method coverage extending to liver and dermatologic pruritus.
• Patent expiration substantially later than FDA NCE exclusivity expiration.

Constraints

• The claims do not appear to cover every kappa opioid receptor agonist.
• The method claims require pruritus treatment and specified disease associations.
• The supplied claims do not recite a specific dose, concentration, dosing interval, vial size, or administration device.
• A generic applicant may pursue a label carve-out for non-protected indications.
• A successful invalidity challenge to claim 1 would materially reduce the value of the dependent formulation claims.

The compound claim is the estate’s central asset. Claims 6 through 9 provide additional infringement theories for injectable formulations, while claims 10 through 18 create label-based barriers.

What generic entry risks exist for Korsuva?

The earliest practical generic-entry window is after August 2026, when the five-year NCE exclusivity period is expected to end. That date does not automatically permit launch because the patent remains in force until the nominal 2034 expiration date.

Scenario 1: Paragraph IV challenge

A generic applicant files an ANDA with a Paragraph IV certification against the listed patent. If the patent holder sues within 45 days, FDA approval may be stayed for up to 30 months, subject to litigation developments and statutory exceptions.[3]

The applicant’s most effective arguments would likely focus on:

• Obviousness of the claimed peptide or salt forms.
• Lack of written description for the full salt, hydrate, and acid salt hydrate scope.
• Enablement across the broad formulation and therapeutic-use language.
• Noninfringement based on an alternative active form or label.
• Invalidity of method claims for lack of patentable distinction over prior clinical or pharmacological disclosures.

Scenario 2: Section viii carve-out

An ANDA applicant removes patented CKD-hemodialysis pruritus language and seeks approval for another indication. This approach would reduce method-of-use exposure but would not avoid claim 1, claim 6, or other composition claims if the product itself contains difelikefalin.

Scenario 3: Post-expiration launch

A generic launches after patent expiration without resolving the patent through litigation or settlement. This is the lowest legal-risk path but delays entry until the mid-2030s unless the patent is invalidated, disclaimed, or otherwise removed.

How does difelikefalin compare with competing pruritus treatments?

Difelikefalin has a distinct patent and regulatory position because it is a defined synthetic peptide with a narrow receptor pharmacology and an FDA-approved dialysis indication.

Treatment	Regulatory position	Patent risk profile	Commercial relevance
Difelikefalin/Korsuva	FDA-approved for CKD-associated pruritus in hemodialysis	Direct compound and use claims through 2034 nominally	Core branded product
Nalfurafine	Approved in Japan for certain uremic and cholestatic pruritus uses	Separate Japanese and international estate	Geographic competitor
Gabapentin or pregabalin	Off-label or condition-specific use	Mature generic market	Price pressure, but not direct substitutes in regulatory status
Nalbuphine and other opioid agents	Various approved uses; pruritus use may be off-label or investigational	Separate compound estates	Clinical and development competition
Biologic therapies for atopic dermatitis	Approved for inflammatory skin disease	Biologic patent and exclusivity frameworks	Relevant to dermatologic pruritus, not dialysis pruritus

Difelikefalin’s primary competitive moat is the dialysis indication rather than broad treatment of all pruritus. The dermatology claims in US 10,793,596 expand legal coverage, but the initial FDA approval and commercial evidence are centered on CKD-associated pruritus.

What manufacturing and geographic barriers affect difelikefalin?

Difelikefalin is a synthetic peptide, so it does not face biosimilar approval risk in the same manner as a monoclonal antibody. A follow-on manufacturer would generally pursue an ANDA or another small-molecule pathway rather than a 351(k) biosimilar application.

Manufacturing barriers remain meaningful:

• Stereochemically correct solid-phase peptide synthesis.
• Control of peptide impurities and deletion sequences.
• Reproducible salt or hydrate formation.
• Sterile aqueous formulation and fill-finish.
• Stability control for an injectable peptide.
• Bioequivalence and product-quality documentation.
• Supply-chain qualification for specialized peptide starting materials.

US Patent 10,793,596 has no automatic worldwide effect. Its compound, formulation, and method claims apply only in the United States. Foreign family members must be analyzed separately for filing status, grant, claim scope, opposition history, and expiration. Market entry in Europe, Japan, Canada, and other jurisdictions cannot be inferred solely from the US patent.

What litigation and settlement issues should investors monitor?

The principal litigation trigger is an ANDA Paragraph IV filing after NCE exclusivity expires. Relevant issues include:

• Whether the patent is listed for the active ingredient, formulation, method, or multiple categories.
• Whether the NDA holder sues within the 45-day period.
• Whether FDA imposes a 30-month stay.
• Whether the generic label carves out hemodialysis pruritus.
• Whether a settlement grants a licensed entry date before November 2034.
• Whether a settlement includes a no-challenge clause or authorized-generic arrangement.
• Whether later patents cover concentration, dosing, device, manufacturing, or new indications.

A settlement could convert the nominal 2034 patent date into an earlier negotiated entry date. Without a public settlement, the principal baseline remains August 2026 for possible ANDA filing and November 2034 for nominal patent expiration.

Key Takeaways

• US Patent 10,793,596 directly claims difelikefalin and broad pharmaceutically acceptable salt, hydrate, hydrochloride, and acetate forms.
• The patent separately protects solid, lyophilized, aqueous, isotonic, and buffered compositions.
• Claims 10 through 18 cover pruritus associated with CKD, hemodialysis, end-stage renal disease, cholestatic liver disease, atopic dermatitis, contact dermatitis, and psoriasis.
• FDA NCE exclusivity is expected to end in August 2026.
• The patent’s nominal expiration is November 25, 2034.
• A section viii carve-out may reduce method-of-use exposure but would not necessarily avoid the compound and composition claims.
• Difelikefalin is a synthetic peptide, so the principal follow-on pathway is an ANDA, not a biosimilar application.
• The highest-value claim is claim 1 because it can reach the active ingredient independently of a specific formulation or indication.
• The most commercially important method claim is claim 12, which covers CKD-associated pruritus in patients undergoing hemodialysis.

FAQs About US Patent 10,793,596 and Difelikefalin

Can a generic avoid US Patent 10,793,596 by using difelikefalin acetate?

Probably not if the product contains the claimed difelikefalin molecule. Claim 3 expressly recites acetate, and claim 1 broadly covers pharmaceutically acceptable salts.

Does a different buffer avoid the formulation claims?

Not necessarily. Claim 6 broadly covers a pharmaceutical composition containing difelikefalin and an excipient or carrier. Claims 7 through 9 add aqueous, isotonic, and buffered embodiments but do not define the entire formulation scope.

Can a generic launch for psoriasis before 2034?

Only if the product and proposed labeling avoid enforceable claims and any other listed patents. Claims 10 and 18 create direct method-of-use exposure for psoriasis-associated pruritus.

Is difelikefalin subject to biosimilar competition?

No. Difelikefalin is a chemically synthesized peptide rather than a biologic approved under the Public Health Service Act. A follow-on product would ordinarily use an ANDA or another small-molecule regulatory route.

What is the most likely first generic-entry strategy?

The most likely strategy is an ANDA filed after NCE exclusivity expires, combined with a Paragraph IV challenge or a label carve-out. A full-label product would face greater exposure because the core dialysis indication is expressly claimed.

References

1. U.S. Food and Drug Administration. (2021). Korsuva (difelikefalin) injection: Prescribing information and approval materials. FDA.

2. U.S. Patent and Trademark Office. (2020). U.S. Patent No. 10,793,596, Difelikefalin compositions and methods of use. USPTO.

3. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. U.S. Food and Drug Administration. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, Hatch-Waxman provisions. FDA.

Drugs Protected by US Patent 10,793,596

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vifor Intl	KORSUVA	difelikefalin acetate	SOLUTION;INTRAVENOUS	214916-001	Aug 23, 2021	AP	RX	Yes	Yes			Y	Y		TREATMENT OF MODERATE-TO-SEVERE PRURITUS ASSOCIATED WITH CHRONIC KIDNEY DISEASE (CKD-AP) IN ADULTS UNDERGOING HEMODIALYSIS (HD)

International Family Members for US Patent 10,793,596

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2064228		301199	Netherlands
European Patent Office	2064228		CA 2022 00045	Denmark
European Patent Office	2064228		PA2022522	Lithuania
European Patent Office	2064228		LUC00282	Luxembourg
European Patent Office	2064228		2022C/546	Belgium
European Patent Office	2064228		C20220035 00379	Estonia