biologics patent protection

8/7/2019 Biologics Patent Protection

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Introduction Introduction of the concept of patent

life cycle management Insights from the pharma industry Key patentability issues in patent

life cycle management The role of formulations in biologics

patent protection Case Studies

Erythropoietin Growth hormone


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The Dilemma The cost to develop a drug or biologic and bring

to market is hundreds of millions of $$$

Patent protection for the basic NCE or protein isgenerally sought very early in the R&D process

Due to the extensive regulatory review period,significant patent term has been lost by the timethe product goes to market


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Patent Life-Cycle Management Strategic use of patents to

maintain product exclusivity andrevenue stream over life of blockbuster drug or biologic

Involves obtaining additionalpatents that extend protectionbeyond the original patentscovering the NCE or biologic per se


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Insights from the Pharma Industry Patent life-cycle management is a

familiar concept for big pharma Hatch-Waxman Act

Recognizes regulatory delay

Allows innovator to extend patent term of single patent up to 5 years

BUT, provides for generic entry immediatelyupon expiration of patent coverage

Generics often seek to market uponexpiration of original patent to NCE


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Insights from Pharma Industry Pharma companies have countered generics by

increasing the breadth and complexity of thepatent fence around their crown jewels traditional protection covered NCE, method of

making, method of using (treating), and apharmaceutical formulation

Today, patents are typically also filed on: New indications Polymorphs Mechanisms of action Combination products/therapies Dosing regimens Dissolution/bio profiles NEW FORMULATIONS 0 very important Methods of stabilizing


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Patentability Issues To obtain an improvement patent, applicant

must show claimed subject matter is novel,nonobvious, etc. over earlier patent to drug or biologic per se Generally not difficult to show novelty

But must be careful regarding inherent anticipation

Focus is generally on obviousness

KSR Intl Co. v. Teleflex Inc., 550 U.S. ___(2007) Supreme Court clarified obviousness Now easier for USPTO to establish prima facie case

of obviousness and shift burden to applicant to proveotherwise


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Patentability Issues

KSR v. Teleflex Improvement must be more than

predictable use of prior art elements Not limited to references dealing with

precise problem addressed Any need or problem known in the field and

addressed by patent can provide reason for combining elements

Obvious to try could be enough insome instances


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Patentability Issues In response to KSR case, USPTO

established training guidelines for examiners

Identified acceptable rationales tosupport prima facie case of obviousness:

A. Combining prior art elementsaccording to known methods to yieldpredictable results


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Patentability Issues USPTO Rationales for Obviousness

B. Simple substitution of one known, equivalentelement for another to obtain predictable results E.g. one known excipient for another?

C. Use of known technique to improve similar products in the same way

Application of technique to similar product must bewithin ordinary skill in art

D. Applying a known technique to a known productready for improvement to yield predictable results

E.g. lyophilization?

E. Obvious to try choosing from a finite number of predictable solutions


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Patentability Issues

Rebutting Obviousness Rejections Submit technical evidence showing that subject

matter claimed in later (improvement) patent could nothave been predicted to work

Show that claimed subject matter (e.g. newformulation) has unexpected advantages (e.g.,increased efficacy, stability, etc.)

Clinical studies provide good opportunities for patenting improvements, since in vivo effect aredifficult to predict


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The Role of Formulations in BiologicsPatent Protection

Although no formal legal/regulatory

framework for approving genericbiologics exists, biologic innovators arealready applying patent life cyclemanagement strategies to extend patentprotection on blockbuster biologics

As in the pharma industry, formulation

patents are essential components of apatent life cycle management strategyfor biologics


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Case Study I Erythropoietin (Amgen) U.S. Pat. No. 4,703,008

Effective filing date 12/13/83 (but 17-year termfrom grant since pre-GATT) Claim 2: A purified and isolated DNA sequence

consisting essentially of a DNA sequenceencoding human erythropoietin .

U.S. Pat. No. 5,547,933 Effective filing date = 12/13/83 (17 year term)

Claim 3. A non-naturally occurring erythropoietinglycoprotein product . . . having glycosylationwhich differs from that of human urinary erythropoietin.


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U.S. Pat. No. 5,597,562 Effective filing date = 6/3/91 (17-year

term) Claim 1: An oral dosage form

comprising the components:(a) GCSF or erythropoietin ;(b) Surfactant(s)(c) Fatty acid(s); and

(d) Enteric material,wherein said components (a), (b) and (c) are

mixed in liquid phase and lyophilized prior tocombination with component (d).

Case Study I: Erythropoietin (Amgen)


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U.S. Pat. No. 5,856,298 Effective filing date = 10/13/89 (17-year

term) Claim 1: An isolated biologically active

erythropoietin isoform having a singleisoelectric point and having a specificnumber of sialic acids per molecule, saidnumber selected from the group

consisting of 1-14 . . . .


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U.S. Pat. No. 7,217,689 Effective filing date = 10/13/89 (17 year

term) Claim 1: An analog of human

erythropoietin . . . comprising an aminoacid sequence which differs from theamino acid sequence of humanerythropoietin . . . by having one or more

additional glycosylation site(s) ascompared to human erythropoietin.


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U.S. Pat. No. 5,661,125 Effective filing date = 08/06/92 (almost 9

years after first patent) (17-year term) Claim 1: A stable pharmaceutical

composition comprising a solution of atherapeutically effective amount of erythropoietin and a preservative selectedfrom the group consisting of benzyl

alcohol, a paraben and phenol or amixture thereof.


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Case Study I: Erythropoietin (Amgen) U.S. Pat. Pub. No. 2006/0264377

Effective filing date = 4/7/00 If issues will expire 4/7/2020 Claim 1: A pharmaceutical composition

comprising:(a) A substantially homogenous preparation of mono-

PEGylated NESP , said mono-PEGylated NESPconsisting of a polyethylene glycol moietyconnected to a NESP moiety solely at the N-terminus thereof;

(b) Fewer than 5% non-pegylated NESP molecules;and

(c) A pharmaceutically acceptable diluent, adjuvantor carrier.

(NESP is a hyperglycosylated EPO analog havingfive changes in the amino acid sequence of rHuEPO which provide for two additionalcarbohydrate chains)


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Case Study II: Growth Hormone (Novo)

U.S. Pat. No. 5,633,352

Effective filing date = 12/9/83 (17-year term) Claim 1: Biosynthetic ripe human growthhormone from pituitary derived human growthhormone.

U.S. Pat. No. 5,547,696 Effective filing date = 10/13/94 (17-year term) Claim 1: A pharmaceutical formulation comprising

a growth hormone in the amount of about 0.1mg/ml to about 40 mg/ml and valine at aconcentration up to about 100 mM.


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U.S. Pat. No. 5,552,385 Effective filing date = 6/5/95 Claim 1: A pharmaceutical formulation

comprising a growth hormone and Lys-Gly-Asp-Ser (SEQ ID No: 1).

U.S. Pat. No. 6,117,984 Effective filing date = 7/12/91

Claim 1: Divalent cation crystals of humangrowth hormone (hGH) or derivativesthereof.


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U.S. Pat. No. 5,849,704

Effective filing date = 12/16/92 Claim 1: A pharmaceutical composition in theform of a lyophilized powder comprising a growthhormone or a derivative thereof and histidine or histidine derivative . . . .

U.S. Pat. No. 6,022,858 Effective filing date = 1/28/92 Claim 1: A pharmaceutical formulation comprising

a human growth hormone pretreated with zinc salt for at least one hour before addition of other components to the formulation and optionallycontaining lysine or calcium ion.


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Conclusions

Patent life-cycle management is the strategicuse of patents to maintain product exclusivityand revenue stream over the life of acommercially valuable drug or biologic

Successful companies will have fully integratedpatent life-cycle and product life cycle programs

Companies should consider strategic patentingboth before and after marketing approval

Formulation patents are particularly effective atextending exclusivity

Effective patent life-cycle management requirescareful attention to the timing of filings and thecontent of the application


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The Role of Formulations in Biologics Patent Protection

Thank You

Timothy J. Shea, Jr.Elizabeth Haanes

Sterne, Kessler, Goldstein & Fox, P.L.L.C.

(202) 772-8679

biologics patent protection

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