finnegan, henderson, farabow, garrett & dunner, llp howard w. levine jennifer s. swan the...

Finnegan, Henderson, Farabow, Garrett & Dunner, LLP

Howard W. LevineJennifer S. Swan

The purpose of these slides is to raise issues for academic discussion in a developing area of the law. They do not make definitive statements on the current status of the law and do not represent the views of FHFGD or any of its past, present, or future clients.

United States Patent Law and Polymorphs

Overview of U.S. Patent Law What is a patent?

What is required to get a patent?

Why are polymorphs patentable?

Infringement of Patents Cases relating to polymorphs

District court’s decision in SB v. Apotex

The Appellate decision in SB v. Apotex

Overview of Presentation

A Patent Is a Contract Between the Patent Holder and the Government. A patent provides the

government, and thus the general public, with a detailed disclosure of the “invention.”

In return for this disclosure, the patent holder receives a 20 year monopoly.

What is a Patent?

UNITED STATES PATENTNo. 6,999,999

To

John Q. Public

A Patent Does Not Give Anyone (even the Patent Owner!) the Right to “Practice” the Invention.

What is a Patent?

Rather, a Patent Gives the Right to Exclude Others from:

makingusingoffering for saleselling, orimporting

the patented invention

What is a Patent?

Patents are provided for in the U.S. Constitution. “The Congress shall have

power….to promote the progress of…[the] useful arts, by securing for limited times to…inventors the exclusive right to their…discoveries.”

Laws governing the issuance of patents are in U.S.C. Title 35.

What is a Patent?

Title 35 U.S.C. Creates Rules for What is a Patentable Invention

What is a Patent?

U.S. Patent 6,293,874

USER-OPERATED AMUSEMENT APPARATUS FOR KICKING THE USER’S BUTTOCKS

What is a Patent?

U.S. Patent 3,538,508

COMBINATION PILLOW AND CRASH HELMET

What is a Patent?

U.S. Patent Des. 302,693

INTEGRAL HANDSET TELEPHONE AND

FLIP-TOP SHOE

What is a Patent?

U.S. Patent 4,995,379

INSTANT FACE LIFT

What is a Patent?

U.S. Patent 5,708,983

INFLATABLE CHEESE WEDGE HAT

What is a Patent?

U.S. Patent 912,152

FIRE-ESCAPE

What is a Patent?

Requirements for patent:Utility (35 U.S.C. § 101)

Novelty (35 U.S.C. § 102)

Nonobviousness (35 U.S.C. § 103)

What is a Patent?

35 U.S.C. § 101 (Utility)“Whoever invents or discovers any new and useful process, manufacture, or composition of matter, or any useful improvement thereof, may obtain a patent thereof, subject to the conditions and requirements of this title.”

Requirements for Obtaining a Patent

UtilityExample of Inventions that are Patentable:

– Processes– Machines– Manufacture– Compositions of matter (Polymorphs)


UtilityExample of Inventions That Are Not Patentable:

– Products naturally occurring in nature– Scientific principles– Laws of nature– Mental processes


Polymorphs and § 101: SB v. Apotex

Case Involved Different Crystalline Forms of Paroxetine Hydrochloride SB demonstrated that one

crystal form converted to a more stable crystal form in the presence of seeds and sufficient water.

SmithKline Beecham v. Apotex, Nos. 03-1285, 2004 WL 868425 (Fed. Cir. April 25, 2004).


Appellate judge expressed the view that the claim covered subject matter that was unpatentable under section 101, because one crystal form converted to a more stable crystal form, without human intervention.

A “naturally occurring process”


However, the majority of judges hearing the case dismissed this view, because the crystal compound was a synthetic, man-made compound, and thus a “composition of matter” eligible for patent protection.

Novelty (35 U.S.C. § 102)Seven subsections

Focus on 102(a) and 102(b).


35 U.S.C. § 102(a) & (b)

Control whether an event or document qualifies as a potentially patent-defeating activity.

Potentially patent-defeating activities are described as “prior art.”

For “prior art” to invalidate a patent, it must describe every “element” of the claimed invention.



A A

B B

C C

What is the difference between 35 U.S.C. § 102(a) and 35 U.S.C. § 102(b)?


35 U.S.C. § 102(a) states:“A person shall be entitled to a

patent unless-(a) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant.”


35 U.S.C. § 102(b) states:“A person shall be entitled to a

patent unless-(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date the application for patent in the United States.”


35 U.S.C. § 102(a):Defines prior work by others that may

prevent an inventor from obtaining a patent.Such prior art includes:

– If the invention was used by others in the US, or– If the invention was already patented or described in a

printed publication in the US or another country.Use of an invention in Europe will not be

prior art under §102(a) unless the use was described in a printed publication or patented.


35 U.S.C. § 102(b)Defines what activities by the inventor himself

may invalidate a patent.An invention cannot be

– patented or described in a printed publication in the United States or foreign country

– used in public or offered for sale in the United States

More than one year before filing the patent application IN THE UNTIED STATES

This one year period is called the “critical period.”


35 U.S.C. § 103 (Non-obviousness)“A patent may not be obtained…if

the differences between the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains.”

Question is how closely the invention as a whole resembles the prior art.


Non-obviousness Structurally similar chemical

compounds held non- obvious if the compound has “unexpected results.”

Novel polymorphs can be patented without showing unexpected properties

Reason: one of ordinary skill cannot predict the structures, properties, or how to make a novel crystal form.


Patent Office rejected a claim to crystalline anhydrous ATMP as obvious over a reference that disclosed amorphous ATMP.

Patent Office: “no patentably significant change in properties or utility.”

C.C.P.A. reversed: “[W]e are not convinced that the references . . . would lead one of ordinary skill . . . to expect that ATMP could exist in a crystalline, anhydrous form . . . ."

In re Irani, 427 F.2d 806 (C.C.P.A. 1970)

Polymorphs and §103: In re Irani

"We think the board failed to address itself to other factors which must be given weight in determining whether the subject matter as a whole would have been obvious, namely, whether the prior art suggests the particular structure or form of the compound or composition as well as suitable methods of obtaining that structure or form."

In re Cofer, 354 F.2d 664, 668 (C.C.P.A. 1966)

Polymorphs and §103: In re Cofer

The patentability of a claim directed to a chemical compound "derives from the structure of the claimed compound in relation to prior compounds.”

“The relevance to patentability of the properties . . . exhibited by the compound is limited to assessing the significance of the structural distinctions of the claimed compound over the prior art."

Zenith Labs., Inc. v. Bristol-Myers SquibbCo., 19 F.3d 1418, 1422 (Fed. Cir. 1994)

Polymorphs and §103: Zenith

35 U.S.C § 112

What must be included in the patent itself:

1) Specification2) Claims


The Specification Must Contain:“a written description of the

invention

. . . in such full, clear, and exact terms as to enable any person skilled in the art to which it pertains . . . to make and use the [invention], and

shall set forth the best mode contemplated by the inventor of carrying out his invention.”

35 U.S.C. §112: Specification

The Claims Applicant “shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.”

35 U.S.C. §112: Claims

The Claims Similar to a fence around a piece of property.

Claim defines the metes and bounds of a patent holder’s property.


Intellectual

Property

Claim


Intellectual Property

Claim

Infringer


Intellectual Property

Claim

InfringerFHFG&D


PolymorphsClaims often Limited by Analytical

Data. – X-ray powder Diffraction Patterns, – Infrared Spectra– DSC

Be Wary of How Much Data to Include in a Claim.


Claim was directed to a “Monohydrate Compound”

Defined by a X-ray Powder Diffractogram, that incorporated into the claim 37 relative intensities.

Zenith Labs., Inc. v. Bristol-Myers SquibbCo., 19 F.3d 1418, 1422 (Fed. Cir. 1994)


Zenith Labs. v. Bristol-Myers Squibb Co., 19 F.3d 1418 (Fed. Cir. 1994) Federal Circuit found no

infringement BMS's reference sample possessed a

different X-ray diffraction pattern than that claimed in the patent.

Only 22 lines corresponded to the lines of the patent claim: "15 of the lines recited in the claim (representing about 40% of the total) were not considered by the [district] court in its comparison."

Infringement

Thus, it is Critically Important to Consider Issues of Infringement When Drafting Claims.

The more detailed the claim, the less property your fence covers and the easier it becomes for other companies to avoid infringement.

Infringement

Infringement: SB v. Apotex

“Crystalline Paroxetine HCl Hemihydrate” New crystalline form of paroxetine

hydrochloride

Contains a 2:1 ratio of paroxetine hydrochloride to water bound in the crystalline structure

“We can’t predict the existence of paroxetine hydrochloride hemihydrate . . . or even if we could, how to make it or what its properties would be.” Testimony of Professor Joel Bernstein.


SmithKline Beecham Corp. v. Apotex Corp., 247 F.Supp.2d 1011 (N.D.Ill. 2003)

Apotex filed an ANDA for approval to market paroxetine hydrochloride anhydrate

SB argued that Apotex’s anhydrate converts to paroxetine hydrochloride hemihydrate


Factors Causing Conversion

Water

Seeds of Hemihydrate

Heat

Force


"Solid-State forms of paroxetine hydrochloride,” Int’l J. of Pharm. 42 (1988) “ . . . a batch of Form II [anhydrate]

which was stable at all conditions showed rapid and complete conversion when 'spiked' with levels from 1% to 5% of Form I [hemihydrate] and stored at 37ºC / 75% RH for 7 days."

experiments with paroxetine HCl tablets demonstrating conversion of anhydrate to hemihydrate


Anhydrate Hygroscopic "HYGROSCOPIC MATERIAL STORE

UNDER NITROGEN IN SEALED CONTAINERS AND AVOID EXPOSURE TO MOISTURE."

Laboratory Studies Samples of anhydrate converted to high

percentages of hemihydrate overnight

Stability Studies Batches of anhydrate converted to

almost entirely hemihydrate when stored at 40ºC and 75% humidity within one month

Evidence from Apotex Documents


Polymorphic Study of batches used to make Defendants' ANDA tablets

Batches stored at 25°C, 60±5% RH

Initial 9 months

Batch 1 Anhydrate 100%

Water content .96%

Hemihydrate 3%

Water content 3.87%


Water content .70%

Hemihydrate 6%

Water content 4.06%


Water content .63%

Hemihydrate 28%

Water content 4.26%


Apotex Arguments

Seeding is “Junk Science” Mechanism not understood

Not widely accepted


“Well, I submit that if one believes in Santa Claus we might believe in these seed crystals . . . .”

Counsel For NovoPharm, Inc.Glaxo v. NovoPharm Trial August 9, 1993


Bulk Supplier improved process Manufacturing steps

Improved storage bags less permeable to water

But, tablet manufacturer . . . Tablets at normal humidity

Sprays tablets with aqueous coating (88% water)

Apotex Arguments (cont.)


District Court rejected Apotex’s attacks on seeding Apotex's contention "that there

is no scientific basis for believing that seeding occurs . . . is obviously wrong."

"Many scientific phenomena are identified before their causal mechanism is understood."


District Court finds that anhydrateconverts to hemihydrate “[T]he greater the heat . . . and the

humidity, the likelier is conversion . . . .” “[T]he presence of hemihydrate seeds in a

batch of anhydrate is likely, provided [normal humidity and temperature], to produce conversion within a short time"

“[G]reater humidity, temperature, or pressure" can convert anhydrate to hemihydrate in amounts greater than a few percent

“[G]iven enough humidity, heat, etc., conversion [to the hemihydrate form] may continue until it reaches 100 percent"


District Court’s Conclusions

Apotex “probably will be 'making' at least some hemihydrate crystals and therefore infringing, at least prima facie, patent 723 . . . ."

“Some conversion from anhydrate to hemihydrate is likely to occur in a seeded facility in which the anhydrate is exposed to air; BCI's plant is seeded; and the anhydrate manufactured there is exposed to nondehumidified air before it leaves the plant.”


District Court still Ruled Against SB

The ‘723 patent notes that hemihydrate is not hygroscopic and thus has certain manufacturing benefits

District court limited claim 1 to only “commercially significant” amounts of hemihydrate

“High double digits to contribute any commercial value”

SB did not establish Apotex will make “high double digits” amounts


Equitable Defense of Seeding? District Court found that SB

was responsible for seeds of hemihydrate

Thus, district court found that Apotex was not responsible for the hemihydrate in its product


SB’s Position on Appeal

Claim 1 contains only four words: “Crystalline Paroxetine Hydrochloride Hemihydrate”

Claim not limited to “high double digit” amounts of hemihydrate

District court found Apotex will likely market “some” hemihydrate

SB should win


Apotex Position on Appeal

District Court’s claim construction correct

Attacks District Court’s findings concerning conversion as clearly erroneous

“In sum, the district court’s apparent fascination with the seeding theory led it to a finding that smacks of alchemy, not chemistry.”


The Federal Circuit Agreed with SB’s Claim Construction “[T]he specification discusses the

superior handling properties of the hemihydrate form that improve the manufacture of PHC. Those references, however, do not redefine the compound in terms of commercial properties, but emphasize that the new compound exhibits favorable characteristics.”


The Federal Circuit Agreed with SB’s Claim Construction “[N]othing in the ‘723 patent limits

that structural compound to its commercial embodiments.”


The Federal Circuit Agreed with SB’s Claim Construction “Thus, reading claim 1 in the

context of the intrinsic evidence, the conclusion is inescapable that the claim encompasses, without limitation, PHC hemihydrate―a crystal form of paroxetine hydrochloride that contains one molecule of bound water for every two molecules of paroxetine hydrochloride in the crystal structure.”


The Federal Circuit Agreed with SB that Apotex will infringe “SmithKline's Experts Applied

the Disappearing Polymorph Theory to Show that Apotex’s PHC anhydrate tablets inevitably convert to hemihydrate when combined with moisture, pressure, and practically ubiquitous PHC seeds.”


THE END

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