FDA & Patent Exclusivities

Maintaining Market Advantage Through Regulatory and Patent Barriers

Chad A. Landmon
Email: cal@avhlaw.com

90 State House Sq. Hartford, CT 06103 (860) 275-8170

950 F Street, N.W. Washington, D.C. 20004 (202) 721-5415

Strategies for Maintaining Exclusivity

l ed e bl e e fi c b i es t ssi n c o a a pir p r c x P l h E A a c o ND rov on nt aun er m tio pti kL tT st A app c e s e n i c i u e l A R n d Co Re ND Ea r At Pat
Basic Applied Clinical Research Research Trials
Regulatory Exclusivity NCE Exclusivity: 5 yrs NDF or MOU: 3 yrs Orphan Drugs: 7 yrs Biologics: 12 yrs Pediatric 6 mo. Extension

4-5 years 30 mo. stay 3-12 years Regulatory Exclusivity 20+ year Patent Term

Patent Barriers: Patent term extensions Life cycle management

New Formulation New Method of Use

Slide 2 of 20

New Chemical Entity

Statutes & Regulations
21 U.S.C. 355(j)(F)(ii):
If an [NDA] for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other [NDA]. . . no application may be submitted. . . [for] five years from the date of the approval of the application. . . except that such an application may be submitted [in] four years. . . if it contains a [PIV] certification of patent invalidity or noninfringement.

21 C.F.R. 314.108:
The regulations give five years of exclusivity for each drug product that contains a new chemical entity. 314.108(b)(2). A new chemical entity is a drug that contains no active moiety that has been approved by FDA in any other new drug application. Active moiety is defined as the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance. 314.108(a).

Slide 4 of 20

New Chemical Entity

5 Year Exclusivity
New moiety
Excludes only those appended portions of the molecule that cause the drug to be an ester, salt or other noncovalent derivative of a previously approved moiety.

Safety and efficacy must be proven ANDA may not be filed for 5 years (4 years if PIV certification)

21 U.S.C. 355(j)(F)(ii)
Slide 3 of 20

Example: Vyvanse (Lisdexamfetamine)

Dextroamphetamine is a known moiety Lisdexamfetamine, once it enters the body, undergoes a chemical conversion to produce dextroamphetamine Lisdexamfetamine is still considered a new chemical entity entitled to 5 years of exclusivity

Amide bond cleaved

Lisdexamfetamine
Slide 5 of 20

Lysine

Dextroamphetamine

Example: Vyvanse (Lisdexamfetamine)

NCE 5 year exclusivity

No New Moiety 3 year exclusivity

Actavis v. FDA, 625 F.3d 760 (D.C. Cir. 2010)

Slide 6 of 20

New Clinical Investigations

3 Year Exclusivity
Known moiety is altered or reformulated
New dosage New extended release formulations Swapped excipients New method of use

New clinical investigations are conducted that are essential to the approval of the application Delays ANDA approval only, not filing.
21 U.S.C. 355(j)(F)(iii)
Slide 7 of 20

Orphan Drugs
7 Year Exclusivity
For rare or orphan diseases:
Affects fewer than 200,000 people, or No reasonable expectation of recovering costs

Exclusivity is with respect to the disease for which the approved drug was designated
Does not matter if drug turns out to be more profitable or treats more people Exclusivity lost for treating a different condition with the drug or if a follow-on drug is clinically superior
21 U.S.C. 360cc
Slide 8 of 20

The Orange Book

Patent owners must list patents associated with listed drugs
Compounds Formulations Polymorphs, Isomers & Salts Methods of Use / Treatment Not methods of manufacture, packaging or unapproved uses

Obligation continues for later-issued patents

21 U.S.C. 355(b)(1)(G)
Slide 9 of 20

ANDA Certifications
ANDA applicants must certify to the FDA with respect to each Orange Book listed patent, that one or more of the following applies:
(I) (II) (III) (IV) no patents are listed; the patent has expired; the date on which the patent will expire; or the patent is invalid or not infringed.

Must give notice to patent owners and NDA holder

21 U.S.C. 355(b)(2) (3)
Slide 10 of 20

The 30 Month Stay

Once ANDA filed, NDA holder has 45 days to bring an infringement action Action triggers a 30 month stay of ANDA approval
Stay ends with district court decision of no infringement or invalidity Need preliminary injunction to extend stay if district court case not finished

21 U.S.C. 355(c)(3)(C)
Slide 11 of 20

180-Day Exclusivity
For the first applicant to file substantially completed ANDA and PIV certification Exclusivity shared for multiple ANDA applicants filing on the same day Various conduct can trigger forfeiture If first filer forfeits, no one gets exclusivity

Slide 12 of 20

Pediatric Exclusivity
Additional 6 Months Exclusivity
FDA issues a request for pediatric studies
Drug sponsor may request FDAs own initiative.

Sponsor performs study & submits report

Study need not be successful

Second pediatric study via a supplemental NDA can receive two exclusivity terms. Six months added to all regulatory and patent exclusivities
21 U.S.C. 355a
Slide 14 of 20

Biologics
12 Year Exclusivity
4 years until follow-on application may be submitted 12 years until follow-on biologic approval Patent information sharing (No Orange Book)
No 30-month stay 180-day notice for follow-on commercial marketing

42 U.S.C. 262(i)
Slide 13 of 20

Patent Term Extension

(Due to PTO delay)
When triggered:
No action within 14 months of filing Response to a reply takes longer than 4 months Pendancy is greater than 3 years

Extension available:
Actual number of days the issuance was delayed Reduced by the time which the applicant failed to engage in reasonable efforts to conclude prosecution of the application.
35 U.S.C. 154(b)
Slide 15 of 20

Patent Term Extension

(Due to FDA regulatory approval)
When triggered:
Must claim a product, a method of using a product, or a method of manufacturing a product subject to a regulatory review period before its 1st commercial marketing or use The term of the patent has not expired The term has not been extended (except for 154(b)

Extension available:
Equal to the regulatory review period for the approved product which period occurs after the date the patent is issued Must justify term extensions on a claim by claim basis Only one patent may be extended per regulatory review period Cannot exceed 5 years and remaining patent term plus extension cannot exceed 14 years

35 U.S.C. 156
Slide 16 of 20

Early Stage Patentable Features

Newly isolated or synthesized chemical compound New chemical derivative, analog, prodrug, or isolated metabolite of a known compound New salt or polymorphic crystal form New formulation with inactive agents New combination of known active agents New disease indication for a known drug

Slide 17 of 20

Late Stage Patentable Features

New target patient population (e.g. children) New route of administration (e.g. transdermal application of an oral medicine) New dosage amount (different from prior art) New dosage regimen (different timing of doses) New combination therapy (different drugs) Degree of purity of the compound

Slide 18 of 20

Strategy: Maintain Exclusivity

Through FDA regulatory schemes
Provides protection even without a patent From 5 to 12 years for pioneer drugs Use the 3 Year Period Pediatric 6 month extensions

Through patents
Patent early, patent often, even if after NDA approved Patent extension schemes Active drug life cycle management

Slide 19 of 20

Questions?
Chad A. Landmon
Email: cal@avhlaw.com

90 State House Sq. Hartford, CT 06103 (860) 275-8170

950 F Street, N.W. Washington, D.C. 20004 (202) 721-5415

Slide 20 of 20

10