Details for Patent: 11,096,983

Which drugs does patent 11,096,983 protect, and when does it expire?

Patent 11,096,983 protects GIAPREZA and is included in one NDA.

This patent has fifty-two patent family members in twenty-four countries.

Summary for Patent: 11,096,983

Title:	Angiotensin II alone or in combination for the treatment of hypotension
Abstract:	The present invention relates, inter alia, to a method comprising administering to a subject having high output shock and undergoing treatment with a catecholamine at a dose equivalent to at least about 0.2 mcg/kg/min of norepinephrine a dose of angiotensin II which is effective to raise the blood pressure of the subject to a mean arterial pressure (MAP) of about 6.5 mm Hg or above, and which is effective to reduce the dose of the catecholamine required to maintain a MAP of about 65 mm Hg to the equivalent of about 0.05-0.2 mcg/kg/min norepinephrine or less, or to the equivalent of about 0.05 mcg/kg/min norepinephrine or less.
Inventor(s):	Lakhmir S. Chawla
Assignee:	George Washington University
Application Number:	US16/382,850
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,096,983
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 11,096,983: Angiotensin II Shock-Treatment Claims, Patent Scope and Competitive Landscape

US Patent No. 11,096,983 protects a dosing protocol for synthetic human angiotensin II, particularly Giapreza, in patients with distributive or septic shock. The central limitation is administration at an initial rate of approximately 20 ng/kg/min followed by downward titration to achieve or maintain a target mean arterial pressure, or MAP, of at least approximately 65 mmHg. Claim 27 adds a narrow formulation combination covering angiotensin II acetate in aqueous sodium chloride with sodium hydroxide and hydrochloric acid at approximately pH 5.5.

The patent is primarily a method-of-use patent. It does not broadly claim the angiotensin II molecule, the amino-acid sequence alone, or every angiotensin II formulation. Its commercial relevance depends on whether a competing product or clinical protocol practices the specified starting dose, titration strategy, shock indication, MAP target and formulation limitations.

What does US Patent 11,096,983 claim?

The patent has three independent claims:

Claim	Independent subject matter	Principal scope
1	Treatment of distributive shock	Human angiotensin II salt; initial rate of about 20 ng/kg/min; downward titration to achieve or maintain MAP of at least about 65 mmHg
24	Treatment of septic shock	Same initial dose and titration framework as claim 1
27	Treatment of septic or distributive shock	Synthetic human angiotensin II, SEQ ID NO. 1, acetate salt, specified excipients, pH of about 5.5, initial 20 ng/kg/min dose and MAP target

Claims 2 through 23 depend from claim 1. Claims 25 and 26 depend from claim 24. The claims collectively cover dose adjustment, administration duration, formulation chemistry, blood-pressure targets, concurrent vasopressors and the identity of the peptide.

The patent’s practical claim structure is:

1. A covered shock condition.
2. Human administration.
3. Angiotensin II in salt form.
4. An initial administration rate of approximately 20 ng/kg/min.
5. Downward titration.
6. A MAP objective of at least approximately 65 mmHg, or in certain dependent claims, at least approximately 80 mmHg.

A product or treatment protocol that omits one of the required elements may fall outside a particular claim, although other patents in the family or broader patent estate may remain relevant.

How broad is claim 1 of US 11,096,983?

Claim 1 is broad in clinical context but specific in dosing sequence. It covers treatment of distributive shock rather than only septic shock. The term “distributive shock” can encompass septic shock and other vasodilatory shock states, depending on the claim construction and clinical facts.

The most important limitations are:

• The patient must be a human subject.
• The subject must have distributive shock.
• The administered agent must be human angiotensin II.
• The agent must be in salt form.
• The initial rate must be “about 20 ng/kg/min.”
• The rate must subsequently be titrated downward.
• The final rate must be sufficient to achieve or maintain MAP of at least about 65 mmHg.

The claim does not require a particular concomitant vasopressor. The patient may be receiving norepinephrine, vasopressin, phenylephrine, epinephrine or dopamine under claims 19 through 21, but concurrent vasopressor treatment is not required by claim 1.

The claim also does not require the commercial brand Giapreza by name. A different manufacturer’s synthetic human angiotensin II product could implicate the claim if it satisfies the claimed clinical and formulation limitations.

What does “about 20 ng/kg/min” mean?

“About” creates a range of potential equivalents around the stated dose. The exact boundaries would depend on the specification, prosecution history, expert evidence and claim construction. The patent does not state in the supplied claim text that the dose must be exactly 20 ng/kg/min.

The claim is therefore directed to a dosing regimen centered on 20 ng/kg/min, rather than to a fixed dose of exactly 20 ng/kg/min. A competing label that instructs an initial dose materially above or below that level may reduce literal infringement risk, but the result would depend on the applicable interpretation of “about” and the full patent record.

What dosing and titration methods are protected?

Claims 2 and 3 add narrower titration ranges:

Claim	Added limitation
2	One or more downward titrations by about 1.25 ng/kg/min to about 15 ng/kg/min
3	Downward titration to about 1.25 ng/kg/min to less than 20 ng/kg/min over one or more titrations

These claims target the post-stabilization phase of treatment. They are narrower than claim 1 because they require particular downward titration behavior or a defined resulting rate.

The claims do not require one specific number of titration steps. “One or more titrations” allows a single reduction or multiple reductions, provided the other numerical limitations are met.

The claimed treatment duration ranges from approximately 0.25 hours to 120 hours under claim 4, with claim 5 narrowing the period to approximately one to seven hours. The duration limitations may be important in assessing infringement because short emergency administration and prolonged critical-care use can fall within different dependent claims.

What formulations are protected by US 11,096,983?

The patent includes formulation limitations, but the strongest formulation protection is concentrated in claims 6 through 11 and claim 27.

Claim	Formulation limitation
6	Angiotensin II acetate salt
7	Parenteral composition containing aqueous sodium chloride
8	Sodium chloride and sodium hydroxide
9	Sodium chloride, sodium hydroxide and hydrochloric acid
10	The composition has pH from about 3.0 to about 9.0
11	The composition has pH of about 5.5
27	Synthetic human angiotensin II, acetate salt, aqueous sodium chloride, sodium hydroxide, hydrochloric acid and pH of about 5.5

Claim 27 is materially narrower than claim 1. To practice claim 27, a competing product or use would need to meet the clinical limitations and the specified composition limitations.

The presence of sodium hydroxide and hydrochloric acid is significant because these ingredients can function as pH-adjusting agents rather than as primary therapeutic components. A competing formulation may avoid claim 27 by using a different salt, a different buffer system or a different pH. That design-around would not necessarily avoid claims 1 or 24 if the competing product still uses angiotensin II salt and the claimed dosing regimen.

What blood-pressure targets are covered?

Claims 12 through 18 expand the MAP limitations:

• Claim 12 covers administration sufficient to achieve MAP of at least about 80 mmHg.
• Claim 13 covers administration sufficient to maintain MAP of at least about 65 mmHg.
• Claims 14 and 15 address maintenance at 65 mmHg for up to six hours or six hours or more.
• Claim 16 covers maintenance of at least about 80 mmHg.
• Claims 17 and 18 divide the 80 mmHg maintenance period at six hours.

These claims provide multiple infringement theories around the clinical endpoint. A treatment protocol can potentially satisfy the 65 mmHg branch without satisfying the 80 mmHg branch. The six-hour limitations create additional distinctions based on duration of MAP maintenance.

Because the claims use “achieve or maintain,” the protocol may be covered whether the target MAP is reached after initiation or sustained after it is reached.

Does the patent cover use with norepinephrine or vasopressin?

Yes. Claims 19 through 21 expressly cover treatment while the patient is receiving one or more vasopressors.

The listed vasopressors are:

• Norepinephrine
• Vasopressin
• Phenylephrine
• Epinephrine
• Dopamine

Claim 21 narrows the combination to norepinephrine or vasopressin. These claims align with the clinical setting in which angiotensin II is used as an adjunct or rescue vasopressor rather than as a first-line replacement for catecholamine therapy.

A competing label that recommends angiotensin II only after norepinephrine or vasopressin failure could therefore remain within the dependent claims.

What peptide and salt forms are required?

Claims 22 and 23 narrow claim 1 to synthetic human angiotensin II and the peptide sequence identified as SEQ ID NO. 1. Claims 25 and 26 impose corresponding limitations on the septic-shock claims.

The patent distinguishes between:

• Human angiotensin II generally.
• Synthetic human angiotensin II.
• Human angiotensin II having SEQ ID NO. 1.
• Angiotensin II in salt form.
• Angiotensin II acetate salt.

The broadest claims require human angiotensin II in salt form. They do not require acetate specifically. Acetate becomes mandatory only in claim 6 and claim 27.

This structure creates a layered estate: a broad active-ingredient and dosing layer, a synthetic-peptide layer, an acetate-salt layer and a formulation-specific layer.

What is the commercial product associated with the patent?

The relevant commercial product is Giapreza, an intravenous angiotensin II product marketed for increasing blood pressure in adults with septic or other distributive shock. The FDA-approved label identifies an initial infusion rate of 20 ng/kg/min and titration based on blood-pressure response, subject to product-specific dosing instructions (U.S. Food and Drug Administration, 2023).

Commercial attribute	Giapreza
Active ingredient	Angiotensin II
Route	Intravenous infusion
Therapeutic category	Vasopressor
Primary use	Blood-pressure support in adults with septic or distributive shock
Initial dose	20 ng/kg/min under the FDA labeling framework
Product type	Synthetic peptide drug
Regulatory pathway	New drug application, not a biologic license application
Primary commercial patent risk	ANDA-based generic competition and method-of-use patent challenges

The match between the FDA-labeled initial dose and claim 1 is commercially important. A generic applicant seeking approval for the same labeled use and dosing regimen could face both listed-patent and non-listed-patent considerations.

When does US Patent 11,096,983 lose exclusivity?

US Patent 11,096,983 issued on August 24, 2021. Patent expiration is determined by the applicable 20-year term measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and any terminal disclaimer. The issue date does not determine expiration.

The patent should be analyzed with the following records:

Exclusivity item	Relevance
Patent term	Earliest effective nonprovisional filing date
PTA	Can extend the nominal term for USPTO delay
PTE	May extend an eligible pharmaceutical patent based on regulatory review
Terminal disclaimer	Can limit the term based on another patent
FDA five-year NCE exclusivity	Relevant to the original approved drug, not automatically to every later patent
Orphan-drug exclusivity	Depends on the approved indication and designation

A precise expiration date requires the USPTO patent file, including PTA and terminal-disclaimer data, together with FDA Orange Book and regulatory-exclusivity records. The claims supplied by the user do not establish those dates.

What is the Orange Book status of Giapreza?

Giapreza is a small-molecule peptide drug regulated through an NDA rather than a biologic license application. Accordingly, a competing applicant would generally pursue an abbreviated new drug application, or ANDA, rather than a biosimilar application under section 351(k) of the Public Health Service Act.

The Orange Book analysis should separate:

1. Patents listed for the approved drug and its formulation.
2. Method-of-use patents and their corresponding use codes.
3. FDA regulatory exclusivity.
4. Patents that are commercially relevant but not listed in the Orange Book.

A method-of-use patent can be listed if it claims an approved method of using the drug and satisfies FDA listing requirements. Listing does not establish validity or infringement. It does, however, create a statutory certification and litigation pathway for ANDA applicants under the Hatch-Waxman Act (FDA, 2024).

Are Paragraph IV challenges or generic lawsuits publicly associated with this patent?

A Paragraph IV challenge would arise if an ANDA applicant certified that a listed patent is invalid, unenforceable or will not be infringed. The principal litigation consequences can include:

• Notice to the patent holder and NDA holder.
• A 45-day period for filing an infringement action.
• A potential 30-month stay of ANDA approval.
• Litigation over claim construction, written description, enablement, obviousness, anticipation and infringement.

The supplied information does not establish a specific Paragraph IV notice, district-court complaint or settlement involving US 11,096,983. Patent litigation status should be confirmed through USPTO Patent Center, PACER, FDA Orange Book updates and SEC disclosures from the relevant patent holders.

Is biosimilar risk relevant to angiotensin II?

No conventional biosimilar pathway is expected for Giapreza because angiotensin II is regulated as a drug under an NDA rather than as a biologic under a BLA. The principal competitive threat is a generic or follow-on drug submitted through section 505(j), not a biosimilar submitted under section 351(k).

The technical barriers to generic entry may still be meaningful. An applicant may need to demonstrate:

• Pharmaceutical equivalence.
• Bioequivalence or an accepted alternative to conventional systemic bioequivalence testing.
• Comparable intravenous delivery.
• Control of peptide purity and degradation products.
• Consistent salt form and solution stability.
• Manufacturing reproducibility.
• Compliance with sterility and endotoxin requirements.

These manufacturing and formulation issues may create practical barriers even where the active peptide sequence is known.

How strong is the patent estate?

The patent estate is strongest against a product that reproduces the Giapreza label and formulation. The risk profile is lower for a product that changes several variables at once.

Competing strategy	Risk under US 11,096,983
Same 20 ng/kg/min starting dose and downward titration	High
Same dose but different shock indication	Fact-dependent
Same angiotensin II sequence in a non-salt form	Potentially reduced
Acetate salt with the claimed excipients and pH	High for claim 27
Different pH-adjustment system	May avoid narrower formulation claims
Different starting dose	May reduce literal infringement risk
Use only outside distributive or septic shock	May avoid the principal claims
Use of a different vasopressor combination	Does not avoid claims 1 or 24 by itself
Different peptide or analog	Potentially outside sequence-specific claims

The broadest commercial threat remains the label-based method claims. A generic applicant cannot freely assume that a formulation design-around eliminates method-of-use risk if the proposed label still instructs the claimed dosing regimen.

What licensing, ownership and settlement issues matter?

The supplied claim text does not identify a licensing agreement, assignment chain, co-development arrangement or settlement. Ownership and enforcement rights should be checked in the USPTO assignment database.

For commercial diligence, the relevant questions are:

• Whether the patent is owned by the NDA holder or an affiliated entity.
• Whether enforcement rights were assigned or licensed.
• Whether the patent is subject to a terminal disclaimer.
• Whether any ANDA settlement restricts launch timing.
• Whether the settlement includes a license, authorized-generic commitment or covenant not to sue.
• Whether the Orange Book listing uses a broad or narrow use code.

No settlement term should be inferred solely from the patent claims or the FDA label.

What generic launch scenarios exist?

Three practical scenarios are most relevant:

Label-preserving launch

The generic uses the same clinical indication, 20 ng/kg/min starting dose and downward titration. This creates the highest method-of-use patent exposure and is the most direct Paragraph IV scenario.

Carve-out launch

The applicant omits a patented indication or dosing instruction from the label under a section viii statement. This may reduce infringement risk but is difficult if the disputed regimen is central to the approved use.

Formulation design-around

The applicant uses a different salt, pH-adjustment system or excipient profile. This approach may avoid claim 27 and other formulation-dependent claims while leaving the dosing claims potentially applicable.

Key Takeaways

• US Patent 11,096,983 is a method-of-use patent focused on angiotensin II treatment of distributive and septic shock.
• The core regimen is an initial dose of about 20 ng/kg/min followed by downward titration to achieve or maintain MAP of at least about 65 mmHg.
• Claim 27 is the narrowest and most formulation-specific claim, requiring synthetic human angiotensin II acetate, aqueous sodium chloride, sodium hydroxide, hydrochloric acid and approximately pH 5.5.
• The patent covers use with norepinephrine, vasopressin and other listed vasopressors through dependent claims.
• Giapreza’s 20 ng/kg/min dosing framework creates direct label overlap with the central claims.
• Generic rather than biosimilar competition is the relevant regulatory pathway.
• Exact expiration, Orange Book listing, Paragraph IV activity, ownership and settlement status require review of current USPTO, FDA and court records.

FAQs

Does US Patent 11,096,983 claim Giapreza by name?

No. The claims use functional and structural limitations, including human angiotensin II, salt form, dose, titration and MAP target. A product can fall within the claims without being marketed under the Giapreza name.

Can a generic avoid the patent by changing the angiotensin II concentration?

Not necessarily. Concentration is not an express limitation in the supplied independent claims. Changing concentration may avoid other formulation claims, but it would not automatically avoid the dosing and treatment limitations.

Does claim 27 cover every angiotensin II acetate formulation?

No. Claim 27 requires the specified clinical method as well as the listed composition elements and approximately pH 5.5. A formulation containing acetate but lacking the claimed excipient or pH combination may fall outside claim 27.

Is septic shock the only covered indication?

No. Claim 1 covers distributive shock broadly, while claim 24 covers septic shock. Claim 27 covers septic shock or distributive shock.

Can a physician’s off-label use create patent infringement risk?

Potentially. Method-of-treatment claims can be implicated by performance of the claimed method, while manufacturer liability may depend on labeling, inducement, distribution conduct and the specific facts. The patent claims alone do not resolve liability for every participant.

References

1. U.S. Patent and Trademark Office. (2021). U.S. Patent No. 11,096,983, Methods of treating shock.
2. U.S. Food and Drug Administration. (2023). Giapreza (angiotensin II) injection prescribing information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
4. U.S. Food and Drug Administration. (2017). Giapreza approval letter and regulatory materials.
5. U.S. Code, 21 U.S.C. § 355. (2024). Federal Food, Drug, and Cosmetic Act, abbreviated new drug applications and patent certifications.
6. U.S. Code, 35 U.S.C. §§ 154, 156. (2024). Patent term and patent-term extension provisions.

Drugs Protected by US Patent 11,096,983

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
La Jolla Pharma	GIAPREZA	angiotensin ii acetate	SOLUTION;INTRAVENOUS	209360-003	Dec 23, 2021		RX	Yes	Yes						TREATING SEPTIC SHOCK WITH ANGIOTENSIN II
La Jolla Pharma	GIAPREZA	angiotensin ii acetate	SOLUTION;INTRAVENOUS	209360-003	Dec 23, 2021		RX	Yes	Yes						TREATING DISTRIBUTIVE SHOCK WITH ANGIOTENSIN II
La Jolla Pharma	GIAPREZA	angiotensin ii acetate	SOLUTION;INTRAVENOUS	209360-001	Dec 21, 2017	AP	RX	Yes	Yes						TREATING DISTRIBUTIVE SHOCK WITH ANGIOTENSIN II

International Family Members for US Patent 11,096,983

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014364528
Australia	2020277230
Australia	2024219851