United States Court of Appeals 

for the Federal Circuit ______________________ 

IN RE: COPAXONE CONSOLIDATED CASES

---------------------------------------------------------------------------------

TEVA PHARMACEUTICALS USA, INC., TEVA 

PHARMACEUTICAL INDUSTRIES, LTD., TEVA 

NEUROSCIENCE, INC., YEDA RESEARCH AND 

DEVELOPMENT CO., LTD.,

Plaintiffs-Appellants

v.

SANDOZ INC., MOMENTA PHARMACEUTICALS 

INC., DR REDDY'S LABORATORIES LTD, DR 

REDDY'S LABORATORIES INC., MYLAN 

PHARMACEUTICALS INC., MYLAN INC., 

SYNTHON PHARMACEUTICALS, INC., SYNTHON 

B.V., SYNTHON S.R.O. BLANSKO, AMNEAL 

PHARMACEUTICALS LLC, AMNEAL 

PHARMACEUTICALS COMPANY GMBH, PFIZER 

INC.,

Defendants-Appellees

______________________ 

2017-1575

______________________ 

Appeal from the United States District Court for the 

District of Delaware in Nos. 1:14-cv-01171-GMS, 1:14-cv01172-GMS, 1:14-cv-01278-GMS, 1:14-cv-01419-GMS, 

1:15-cv-00124-GMS, 1:15-cv-00306-GMS, Judge Gregory 

M. Sleet.
2 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

______________________ 

Decided: October 12, 2018

______________________ 

 JOHN C. O'QUINN, Kirkland & Ellis LLP, Washington, 

DC, argued for plaintiffs-appellants. Also represented by 

LESLIE M. SCHMIDT, New York, NY; ELIZABETH HOLLAND, 

Goodwin Procter LLP, New York, NY; WILLIAM G. JAMES,

II, WILLIAM M. JAY, Washington, DC; DARYL L. WIESEN, 

Boston, MA.

 DEANNE MAYNARD, Morrison & Foerster LLP, Washington, DC, argued for defendants-appellees. Defendantsappellees Sandoz Inc., Momenta Pharmaceuticals Inc.

also represented by SETH W. LLOYD; WILLIAM A. RAKOCZY, 

MATTHEW V. ANDERSON, THOMAS EHRICH, ERIN FORBES,

CHRISTOPHER PATRICK GALLIGAN, DEANNE M. MAZZOCHI,

RACHEL WALDRON, Rakoczy Molino Mazzochi Siwik LLP, 

Chicago, IL. 

SHANNON BLOODWORTH, Perkins Coie, LLP, Washington, DC, argued for defendants-appellees. Defendantsappellees Mylan Pharmaceuticals Inc., Mylan Inc. also 

represented by ROBERT SWANSON, BRANDON MICHAEL 

WHITE; DAVID LEE ANSTAETT, Madison, WI; DAN L.

BAGATELL, Hanover, NH; CHRISTINA JORDAN 

MCCULLOUGH, Seattle, WA.

 FRANK D. RODRIGUEZ, Budd Larner, P.C., Short Hills, 

NJ, for defendants-appellees Dr. Reddy’s Laboratories 

Ltd, Dr. Reddy’s Laboratories Inc. Also represented by 

ELLEN TCHORNI LOWENTHAL, LOUIS HARRY WEINSTEIN. 

 EDWARD ANTHONY FIGG, Rothwell, Figg, Ernst & 

Manbeck, PC, Washington, DC, for defendants-appellees 

Synthon Pharmaceuticals, Inc., Synthon B.V., Synthon 

S.r.o. Blansko. Also represented by SETH EDWARD 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 3

COCKRUM, SHARON DAVIS, JENNIFER NOCK, BRETT ALAN 

POSTAL. 

 ANTHONY JAMES FITZPATRICK, Duane Morris LLP, 

Boston, MA, for defendants-appellees Amneal Pharmaceuticals LLC, Amneal Pharmaceuticals Company GmbH, 

Pfizer Inc. Also represented by VINCENT CAPUANO,

CHRISTOPHER S. KROON; PATRICK GALLAGHER, Boca Raton, 

FL.

______________________ 

Before REYNA, BRYSON, and STOLL, Circuit Judges.

REYNA, Circuit Judge. 

Plaintiffs-Appellants Teva Pharmaceuticals USA, 

Inc., Teva Pharmaceutical Industries, Ltd., Teva Neuroscience, Inc., and Yeda Research and Development Co., 

Ltd., appeal the decision of the United States District 

Court for the District of Delaware invalidating all asserted claims of patents directed to COPAXONE® 40mg/mL, a 

product marketed for treatment of patients with relapsing 

forms of multiple sclerosis. Because the district court 

correctly held the asserted claims invalid as obvious 

under 35 U.S.C. § 103, we affirm.1 

 

1 In a companion case decided today, Yeda Research 

& Development Co., v. Mylan Pharmaceuticals Inc., Nos. 

17-1594, 17-1595, 17-1596 (Fed. Cir. Oct. 12, 2018), Yeda 

Research and Development Co. appealed from the Patent 

Trial and Appeal Board’s final written decisions finding 

all claims of U.S. Patent Nos. 8,232,250, 8,399,413, and 

8,969,302 unpatentable as obvious in three related inter 

partes review proceedings.
4 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

BACKGROUND

I. Patents at Issue

Yeda Research & Development Co., Ltd. is the assignee of U.S. Patent Nos. 8,232,250, 8,399,413, 8,969,302, 

and 9,155,776 (the ’250, ’413, ’302, and ’776 patent, respectively), all entitled “Low Frequency Glatiramer 

Acetate Therapy.” The patents, collectively referred to as 

the “Copaxone patents,” share a common specification and 

claim priority to the same two provisional applications. 

J.A. 57–69. The earliest priority date of the Copaxone 

patents is August 20, 2009. J.A. 23. 

The Copaxone patents describe and claim 

COPAXONE® 40mg/mL, a treatment for relapsingremitting multiple sclerosis (“RRMS”). RRMS is a form of 

multiple sclerosis, an autoimmune disorder that causes 

the body’s immune system to attack the central nervous 

system. RRMS is characterized by unpredictable relapses 

followed by periods of remission with no new signs of 

disease activity. 

The active ingredient in COPAXONE® 40mg/mL is 

glatiramer acetate (“GA”), a synthetic mixture of polypeptides. GA is also known as “copolymer 1” or “Cop. 1.” 

COPAXONE® 40mg/mL is supplied as a single-dose 

prefilled syringe. Broadly, the treatment consists of the 

injection of 40mg of GA three times a week, abbreviated 

“40mg GA 3x/week.” Relevant to this appeal, side effects 

of GA injections include injection-site reactions (“ISRs”) 

and immediate post-injection reactions (“IPIRs”). ISRs 

are physical symptoms at the injection site, such as 

swelling or itchiness. IPIRs are reactions immediately 

following an injection, such as flushes, sweating, or palpitations. 

Prior to COPAXONE® 40mg/mL, in 1996 the Food and 

Drug Administration (“FDA”) approved COPAXONE®

20mg/mL, a regimen consisting of the daily injection of 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 5

20mg GA. Daily GA injections were known to subject 

patients to discomfort, including side effects in the form of 

ISRs and IPIRs. J.A. 20692. 

For analyzing the obviousness of the Copaxone patents in this case, a key limitation of the asserted claims 

is the administration of a 40mg GA dose in three subcutaneous injections over seven days. Claim 1 of the ’250 

patent is representative: 

1. A method of alleviating a symptom of relapsing-remitting multiple sclerosis in a human 

patient suffering from relapsing-remitting multiple sclerosis or a patient who has experienced a 

first clinical episode and is determined to be at 

high risk of developing clinically definite multiple 

sclerosis comprising administering to the human 

patient a therapeutically effective regimen of 

three subcutaneous injections of a 40 mg dose of 

glatiramer acetate over a period of seven days 

with at least one day between every subcutaneous 

injection, the regimen being sufficient to alleviate 

the symptom of the patient. 

’250 patent col. 16 ll. 35–45.

Apart from claim 1 of the ’302 patent,2 all asserted independent claims require at least one day between doses. 

’250 patent col. 16 ll. 35–45, col. 17 l. 25–col. 18 l. 6; ’413 

patent col. 16 ll. 26–36, col. 18 ll. 14–28; ’302 patent 

col. 17 ll. 4–12; ’776 patent col. 16 ll. 35–50, col. 16 l. 61–

col. 17 l. 19, col. 17 ll. 37–54, col. 17 l. 65–col. 18 l. 22. 

 

2 Claim 1 of the ’302 patent does not specify any 

particular interval between doses. ’302 patent col. 16 ll. 

37–41. Independent claim 10 of the ’302 patent requires 

that the injection be administered “three times per week 

with at least one day between every subcutaneous injection.” Id. col. 17 ll. 4–12. 
6 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

Certain dependent claims of the ’250, ’413, and ’776

patents further require improved tolerability and/or 

reduced frequency of injection reactions in the claimed 

regimen as compared to a 20mg GA daily regimen. See, 

e.g., ’250 patent col. 17 ll. 21–24, col. 18 ll. 7–15; ’413 

patent col. 16 ll. 51–54; ’776 patent col. 16 ll. 51–54, col 17 

l. 65–col. 18 l. 25.. 

The ’776 patent contains additional limitations, namely, the requirement that the 40mg GA 3x/week regimen 

“reduce[] severity of injection site reactions” compared to 

a 20mg daily regimen, as seen in claim 1: 

1. A method of treating a human patient suffering from a relapsing form of multiple sclerosis, 

while inducing reduced severity of injection site 

reactions in the human patient relative to administration of 20 mg of glatiramer acetate s.c. daily, 

the method consisting of one subcutaneous injection of 1 ml of a pharmaceutical composition comprising 40 mg of glatiramer acetate on only each 

of three days during each week of treatment with 

at least one day without a subcutaneous injection 

of the pharmaceutical composition between each 

day on which there is a subcutaneous injection, 

wherein the pharmaceutical composition is in a 

prefilled syringe, and wherein the pharmaceutical 

composition further comprises mannitol and has a 

pH in the range 5.5 to 7.0, so as to thereby treat 

the human patient with reduced severity of injection site reactions relative to administration of 

20 mg of glatiramer acetate s.c. daily. 

’776 patent col. 16 ll. 35–50 (emphasis added).
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 7

II. Prior Art References

The first clinical trial for using GA to treat multiple 

sclerosis took place in 1987 by Dr. Bornstein et al. (“Bornstein”),3 which was followed by a Teva Phase III clinical 

trial in 1995. Both Bornstein and the Phase III trial 

tested 20mg GA daily. J.A. 20378–84, 20464–20782. 

Since GA was developed in an expedited manner under 

orphan drug status in the United States at a time when 

no other disease modifying multiple sclerosis treatments 

were available, the 20mg/day dose was selected without 

performing conventional optimal-dose-finding studies. 

J.A. 24967.

The Bornstein study showed that GA administered 

subcutaneously for two years at a daily dose of 20mg 

“produced clinically important and statistically significant 

beneficial effects.” J.A. 20383. Participants in both 

Bornstein and the Phase III trial reported ISRs and IPIRs 

as side effects. J.A. 20383, 20480. The Phase III trial 

noted “adverse experience” as the main reason contributing to patient dropout, and “[t]he most common adverse 

event associated with dropout was injection site reaction.” 

J.A. 20480. A Phase III trial reviewer made recommendations for future researchers to explore dose-response and 

dose-ranging studies, asking “Is 20 mg the optimum dose? 

Are daily injections necessary?” J.A. 20502.

In 1996, following both Bornstein and the Phase III 

clinical trial, FDA approved Teva’s New Drug Application 

(“NDA”) for COPAXONE® 20mg, 20mg GA injected daily. 

In its 1996 Summary Basis of Approval (“SBOA”), FDA 

recommended that Teva “evaluate the necessity of daily 

[GA] injections as opposed to more infrequent intermit-

 

3 Murray B. Bornstein et al., A Pilot Trial of COP 1 

in Exacerbating-Remitting Multiple Sclerosis, 317 New 

Eng. J. Med. 408, 408–14 (1987).
8 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

tent administration of the drug” because the daily dosing 

regimen “seems like it would subject the patient to an 

excessive amount of discomfort if it is not necessary to 

maintain efficacy.” J.A. 20692. 

A 2002 study by Flechter et al.4 (“Flechter”) evaluated 

the treatment of RRMS with 20mg of GA administered 

every other day. J.A. 20436–40. Flechter concluded that 

“alternate-day treatment with Copolymer 1 is safe, well 

tolerated, and probably as effective as daily Copolymer 1 

in reducing relapse rate and slowing neurologic deterioration.” J.A. 20440. Flechter also noted that patient dropout rates decreased when GA was administered every 

other day as opposed to daily. J.A. 20440 (“It should be 

stressed that the dropout rate was lower in the alternateday group than in the daily-injection regime (39.7% 

versus 60.3%, p < 0.01).”).

Cohen,5 published in 2007, was a “double-blind, dosecomparison study of glatiramer acetate in relapsingremitting MS.” J.A. 20388–95. Cohen compared daily 

subcutaneous injections of 20mg and 40mg GA dosages, 

and concluded that the 40mg dose may be “more effective” 

than the 20mg dose “in reducing MRI activity and clinical 

relapses.” J.A. 20389. Cohen also noted that the onset of 

action of the 40mg dose is more rapid compared to 20mg. 

J.A. 20394. ISRs were the most frequent adverse event 

for both doses, occurring at roughly equal rates. J.A. 

20392–93. IPIRs occurred more frequently in the 40mg 

group than the 20mg group. Id. Cohen thus concluded 

 

4 Shlomo Flechter et al., Copolymer 1 (Glatiramer 

Acetate) in Relapsing Forms of Multiple Sclerosis: Open 

Multicenter Study of Alternate-Day Administration, 25 

Clinical Neuropharmacology 11, 11–15 (2002).

5 J.A. Cohen et al., Randomized, Double-Blind, 

Dose-Comparison Study of Glatiramer Acetate in Relapsing-Remitting MS, 68 Neurology 939, 939–44 (2007). 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 9

that the overall safety and side effect profile of the 40mg 

dose was “similar” to the 20mg dose, but “was associated 

with a greater incidence of certain adverse effects.” J.A. 

20394. 

Teva’s own prior art patent application, International

Patent Application No. WO 2007/081975, Method of 

Treating Multiple Sclerosis (“Pinchasi”), was published 

shortly after the Cohen study. J.A. 20925–56. Pinchasi 

discloses a 40mg GA, every other day dosing regimen for 

the treatment of RRMS. Pinchasi cites to the data from 

Cohen to conclude that “[t]he increased efficacy observed 

with 40 mg/day GA in reducing MRI-measured disease 

activity and relapse rate indicates that it is well tolerated 

and can improve the treatment of RRMS patients. The 

improvement in efficacy, however, is not accompanied by 

a corresponding increase of adverse reactions which 

would be expected upon a doubling of the administered 

dose.” J.A. 20944. 

The FORTE study,6 published in 2008, evaluated the 

safety, tolerability, and efficacy of 40mg GA compared to 

20mg GA. J.A. 20411, 20414–22. FORTE concluded that

both the 40mg and 20mg doses “were equally effective in 

reducing clinical relapses and MRI activity,” and that the 

40mg dose has a “safety profile similar to that observed in 

previous studies of 20mg GA.” J.A. 20411. FORTE also 

confirmed Cohen’s finding that the 40mg dose provided an 

earlier onset of action. J.A. 20422 (noting a “[t]rend for 

an earlier effect of high [40mg] dose on MRI activity”).

 

6 Giancarlo Comi, Jeffrey A. Cohen, Massimo Filippi for the FORTE Study Group, Results from a Phase III, 

One-Year, Randomized, Double-Blind, Parallel-Group, 

Dose-Comparison Study with Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis, 14 Multiple Sclerosis S299, S299–S301 (2008). 
10 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

A 2008 study by Omar Khan and others7 (“Khan 

2008”) compared the effect of daily versus every other day 

administration of 20mg GA subcutaneous injections for 

the treatment of RRMS. J.A. 20883. The study abstract 

noted that although the recommended dose for treating 

RRMS is daily 20mg GA injections, “the optimal dose 

remains unknown” and that there is “considerable interest in alternate dosing regimens of GA” because daily 

injections “can be challenging for long-term patient compliance.” J.A. 20883. Thirty patients were randomly 

assigned to receive 20mg GA dosed daily or every other 

day. After two years, there were “no differences” between 

the two groups in relapse rate or disease progression. 

J.A. 20883. Additionally, after the first two years elapsed, 

patients in each group were given the option to continue 

or switch groups, and were monitored for an additional 

two years. Every patient in the daily group opted to 

switch to every other day administration. After four 

years, there was no difference between the crossover 

group and the group that was always dosed every other 

day. The Caon reference,8 published in 2009, reports the 

same data from the Khan 2008 study, but further noted 

that “[i]njection related lipoatrophy was significantly less” 

in the every other day group. J.A. 20386. 

 

7 Omar Khan et al., Randomized, Prospective, 

Rater-Blinded, Four-Year, Pilot Study to Compare the 

Effect of Daily Versus Every-Other-Day Glatiramer Acetate 

20 Mg Subcutaneous Injections in Relapsing-Remitting 

Multiple Sclerosis, 14 Multiple Sclerosis S296, S296

(2008).

8 Christina Caon et al., Randomized, Prospective, 

Rater-Blinded, Four Year Pilot Study to Compare the 

Effect of Daily Versus Every Other Day Glatiramer Acetate 

20 mg Subcutaneous Injections in RRMS, 72 Neurology

(Suppl. 3) A317 (2009).
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 11

III. State of the Art References

There are two additional references relevant to this 

appeal, a 2009 study by Omar Khan9 (“Khan 2009”) and 

Teva’s own Glatiramer Acetate Low-frequency Administration (“GALA”) Phase III trial of 40mg GA administered three times per week. J.A. 23904–05, J.A. 8246–

8417. Khan 2009 and GALA were both published after 

August 20, 2009, the priority date of the asserted patents, 

and thus do not qualify as statutory prior art. 

The district court admitted the Khan 2009 reference 

for the limited purpose of showing the state of the art at 

the time of the invention. In re Copaxone Consolidated 

Cases, No. 14-1171-GMS, 2017 WL 401943, at *14 (D. Del. 

Jan. 30, 2017). Khan 2009 was published three weeks 

after August 20, 2009, the priority date of the Copaxone 

patents, but the study began two years earlier. J.A. 

23904–05. The study abstract noted that “[t]here is 

considerable interest in studying a more patient friendly 

dosing regimen of GA that may be as efficacious and 

better tolerated than daily GA.” J.A. 23904. Following 

the results of Khan 2008, which showed that alternate 

day administration of GA appears to be as effective as 

daily administration, Khan 2009 compared 20mg GA

administered twice a week to 20mg GA administered 

daily in a pilot, prospective, randomized, and raterblinded two-year study. J.A. 23904. 

Concerning GALA, the district court recognized that 

the GALA trial protocol does not qualify as prior art. In 

re Copaxone, 2017 WL 401943, at *20. Instead, the dis-

 

9 O. Khan et al., Glatiramer Acetate 20mg Subcutaneous Twice-Weekly Versus Daily Injections: Results of a 

Pilot, Prospective, Randomised, and Rater-Blinded Clinical and MRI 2-Year Study in Relapsing-Remitting Multiple Sclerosis, 15 Multiple Sclerosis S249, S249–50 (2009).
12 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

trict court admitted GALA as an admission by Teva to 

inform on the motivations of those having ordinary skill 

in the art at the time of the invention. In its submission 

to FDA, Teva explained that, after the FORTE study 

demonstrated that the 40mg dose was equally effective as 

the 20mg dose, “the natural next step [was] to reduce the 

dosing regimen of GA and find the optimal regimen that 

[would] improve the convenience of treatment and reduce 

the burden and adverse events associated with daily 

subcutaneous injections.” J.A. 8266. Citing the smallscale studies with 20mg GA in the prior art, such as Khan 

2008, GALA noted that results “demonstrated effects in 

relapse rate reduction which were comparable to daily 

injections of GA 20mg, suggesting a lower injection frequency can be considered.” J.A. 8266, 8352. The GALA 

protocol selected a dosing regimen of 40mg GA 3x/week, 

in part because “the subjects will receive approximately 

the same weekly dose, given by 3 subcutaneous injections 

instead of with a daily injection frequency of 7 injections.” 

J.A. 8266. 

IV. Proceeding Below

This appeal arises out of five consolidated district 

court cases. The Defendants-Appellees in this case are 

generic drug manufacturers who (prior to the expiration 

of the Copaxone patents) submitted Abbreviated New 

Drug Applications (“ANDAs”) to FDA for approval to 

engage in the manufacture and sale of generic versions of 

COPAXONE® 40mg administered 3 times per week. In re 

Copaxone, 2017 WL 401943, at *1–10. Appellants Teva 

Pharmaceuticals USA, Inc., Teva Pharmaceutical Industries, Ltd., Teva Neuroscience, Inc., and Yeda Research 

and Development Co., Ltd. (collectively, “Teva”) sued 

Appellees in the United States District Court for the 

District of Delaware, alleging that their respective ANDA 

filings infringed claims 1, 5, 13–17 of the ’250 patent, 

claims 1, 7, 15, and 20 of the ’413 patent, claims 1, 10, and 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 13

11 of the ’302 patent, and claims 1, 2, 5, 6, 9, 12, 16, and 

17 of the ’776 patent. Id. 

Following a Markman hearing, the district court entered a claim construction order. In re Copaxone 40 Mg, 

No. 14-1171-GMS, 2016 WL 873062, at *1–2 (Mar. 7, 

2016) (“Claim Construction Order”). Relevant to this 

appeal, the district court construed the ’250 and ’413 

patents’ “sufficiency”10 terms and the ’776 patent’s “reduced frequency of relapses”11 and “effectiveness”12 terms 

as non-limiting statements of intended effect. Id. at *1 & 

nn.1–2.

The district court held a seven-day bench trial during 

which it considered the invalidity of the asserted claims of 

the Copaxone patents. The district court found that a 

40mg GA dose was explicitly disclosed in references that 

predate the Copaxone patents, specifically Cohen, 

Pinchasi, and FORTE. In re Copaxone, 2017 WL 401943, 

at *14. The court rejected Teva’s arguments that Cohen 

and FORTE taught away from a 40mg dose, and that a 

person of ordinary skill in the art (“POSITA”) would have 

thought that 20mg was the optimal dose. Id. at *14–15. 

The district court also found that, as of the priority date, 

POSITAs knew that daily injections were difficult to 

tolerate based on the 1996 FDA SBOA, Flechter, and 

 

10 E.g., ’250 patent col. 16 ll. 44–45 (“the regimen being sufficient to alleviate the symptom of the patient”); 

’413 patent col. 16 ll. 35–36 (“the regimen being sufficient 

to reduce the frequency of relapses in the patient”).

11 E.g., ’776 patent col. 17 ll. 20–22 (“which reduces 

brain atrophy and for reducing the frequency of relapses 

by 30% or more as compared to placebo in a human population”). 

12 E.g., ’776 patent col. 17 ll. 39–40 (“which is as effective as administration of 20 mg of glatiramer acetate 

s.c. daily”). 
14 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

Khan 2008. Id. at *15–16. Relying in part on trial testimony, the district court found that POSITAs were familiar with the adverse reactions, pain, and treatment 

adherence problems associated with daily injections, and 

would have been motivated to pursue less frequent dosing 

with a reasonable probability of success. Id. at *16. The 

district court found that Pinchasi is the closest prior art 

because it discloses a dosing regimen that differs from the 

claimed regimen by only one dose every two weeks. Id. at 

*17.

In light of these factual findings, the district court 

concluded that a 40mg GA 3x/week dosage would be 

obvious to try, noting that there were only two tested 

dosage amounts in the prior art—20mg and 40mg—and

that researchers were pursuing less frequent dosing 

regimens while recognizing there are a limited number of 

days in a week on which to test frequency. See id. at *19. 

The court recognized that obvious-to-try logic is not 

always appropriate, but found that “[h]ere, there was 

market pressure to solve a known problem—the fact that 

many MS patients could not tolerate daily injections—and 

there were a finite number of predictable solutions that a 

person of ordinary skill in the art would have good reason 

to pursue.” Id. The district court cited to Khan 2009, 

Teva’s GALA study, and trial testimony as evidence of the 

motivations of POSITAs at the time of the invention, and 

noted evidence and testimony supporting the proposition 

that a dosing schedule based on three predetermined days 

each week is preferable for patients over an every other 

day schedule. Id. at *20. The district court highlighted 

testimony from Dr. Green that a regimen of injections on 

three pre-determined days of each week is more convenient for patients and has better patient adherence than an 

every other day regimen, in which the days on which 

patients inject differ depending on the week. Id. The 

district court also noted a study showing that Rebif®, an 

injectable MS treatment dosed three times a week, has 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 15

increased patient adherence compared to the daily 20mg 

GA regimen. Id. 

In light of additional testimony that a POSITA would 

expect the number of ISRs to decrease as the number of 

injections per week decreased, as well as disclosures in 

Flechter, Khan 2008, and Caon, the district court held 

obvious the dependent claims of the ’250 and ’413 patents 

requiring that the 40mg GA 3x/week regimen reduce the 

frequency of ISRs and IPIRs as compared to a 20mg/day 

regimen. Id. at *17–18. The district court also found 

obvious claim 15 of the ’250 patent, which requires the 

claimed method improve tolerability as compared to a 

20mg/day regimen. Id. at *17. The court further determined the claims of the ’776 patent to be obvious in light 

of Caon and expert evidence presented at trial. Id. at 

*22–23. Finally, the court considered objective indicia of 

nonobviousness, and concluded that none of them warranted a finding of nonobviousness of the Copaxone 

patents. Id. at *25.

Following its analysis, the district court held all asserted claims of the Copaxone patents invalid as obvious 

under § 103. Teva appeals the district court’s claim 

construction and obviousness decisions. We have jurisdiction pursuant to 28 U.S.C. § 1295(a)(1). 

DISCUSSION

I. Claim Construction

Claim construction seeks to ascribe the “ordinary and 

customary meaning” to claim terms as a person of ordinary skill in the art would have understood them at the 

time of invention. Phillips v. AWH Corp., 415 F.3d 1303, 

1312–14 (Fed. Cir. 2005) (en banc) (citing Vitronics Corp. 

v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)). 

Where the district court’s claim construction relies only on 

intrinsic evidence, as is the case here, the construction is 

a legal determination reviewed de novo. Poly-Am., L.P. v. 
16 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

API Indus., Inc., 839 F.3d 1131, 1135–36 (Fed. Cir. 2016) 

(citing Teva Pharm. USA, Inc. v. Sandoz, Inc., 135 S. Ct. 

831, 841 (2015)). 

Teva contends that the district court erroneously construed certain claim terms as non-limiting and disregarded them for nonobviousness purposes. Teva points to the 

“sufficiency” terms of the ’250 and ’413 patents as being 

limiting. Claim 1 of the ’250 patent recites “A method of 

alleviating a symptom of relapsing-remitting multiple 

sclerosis . . . comprising administering to the human 

patient a therapeutically effective regimen . . . , the regimen being sufficient to alleviate the symptom of the patient.” ’250 patent col. 16 ll. 35–45 (emphasis added). 

Similarly, claims 1 and 20 of the ’413 patent both recite 

“[a] method . . . comprising administering to the human 

patient a therapeutically effective dosage regimen . . . , 

the regimen being sufficient to reduce the frequency of 

relapses in the patient.” ’413 patent col. 16 ll. 26–36, 

col. 18 ll. 14–27 (emphasis added). Teva also contests the 

district court’s construction of the “reduced frequency of 

relapse” terms and “effectiveness” terms in the ’776 

patent as non-limiting. For example, claim 5 of the 

’776 patent describes “a method for reducing the frequency of relapses”; claims 6, 16, and 17 contain similar limitations. ’776 patent col. 16 ll. 61–65, col. 17 ll. 20–22, 65–

66, col. 18 ll. 23–25. Claim 12 describes “[a] method for 

improving the tolerability of glatiramer acetate treatment 

of a human patient suffering from a relapsing form of 

multiple sclerosis which is as effective as administration 

of 20 mg of glatiramer acetate s.c. daily,” and claims 16 

and 17 contain similar limitations. Id. col. 17 ll. 36–40

(emphasis added), col. 17 l. 65–col. 18 l. 5, col. 18 ll. 23–

25. 

The district court construed these terms to be nonlimiting statements of intended effect, holding that those 

terms are “strikingly similar to those in the patents in 

Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc., 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 17

246 F.3d 1368 (Fed. Cir. 2001).” Claim Construction 

Order, 2016 WL 873062, at *2 n.2. In Bristol-Myers, the 

court held that certain terms were non-limiting because 

they “merely express[ed] a purpose” and “only state[d] an 

intended result of the claimed method.” 246 F.3d at 

1374–75. The court stated that express dosage amounts 

are material claim limitations, but statements of intended 

results from their administration, such as “an antineoplastically effective amount,” “does not change those 

amounts or otherwise limit the claim.” Id. at 1375. Claim 

language without any bearing on the claimed methods 

should be deemed non-limiting when it does not result in 

“a manipulative difference in the steps of the claim.” Id. 

at 1376.

We see no meaningful difference between the claims 

in Bristol-Myers and those at issue here. The phrase “the 

regimen being sufficient to reduce the frequency of relapses in the patient” does not change the express dosing 

amount or method already disclosed in the claims, or 

otherwise result in a manipulative difference in the steps 

of the claims. The claims are clear that the dosing has to 

be “therapeutically effective regimen”; the addition of “the 

regimen being sufficient to” be therapeutically effective is 

superfluous, does not change the claimed method or 

require any additional required structure or condition for 

the claims, and is therefore non-limiting. 

Teva argues that the “‘sufficiency’ terms were added 

during prosecution to overcome rejections.” Appellants’ 

Opening Br. 74. Teva overstates the intrinsic record. 

Claim 1 of the ’250 patent was amended to overcome a 

§ 112 rejection based on the examiner’s read of the claims 

prior to amendment as permitting only a single seven-day 

period of administration, rather than an ongoing treatment regimen. See J.A. 26417–18, 26464–65 (same, for 

the ’413 patent). The claim was amended to replace the 

ambiguous “therapeutically effective dose” with “therapeutically effective regimen of,” as follows: 
18 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

1. (Currently Amended) A method of alleviating a symptom of relapsing-remitting multiple 

sclerosis in a human patient suffering from relapsing-remitting multiple sclerosis or a patient 

who has experienced a first clinical episode and is 

determined to be at high risk of developing clinically definite multiple sclerosis comprising administering to the human patient a therapeutically 

effective regimen of three subcutaneous injections 

of a therapeutically effective 40mg dose of glatiramer acetate over a period of seven days with at 

least one day between every subcutaneous injection, the regimen being sufficient so as to thereby 

alleviate the symptom of the patient.

J.A. 26430. 

“As amended the claims cannot be reasonably construed to read on only a single seven day period of administration, at least because the claims as amended require 

a ‘regimen.’” J.A. 26436; see also J.A. 26483 (same, for the 

’413 patent). Given this evidence, the addition of “a 

therapeutically effective regimen” would have alone been 

sufficient to overcome the rejection, and thus we are 

unpersuaded by Teva’s contention that addition of the 

“regimen being sufficient . . .” term was necessary or 

relevant to the examiner’s approval. Accordingly, we find 

no error in the district court’s construction. 

II. Obviousness under 35 U.S.C. § 103

Under 35 U.S.C. § 103(a), a patent may not be obtained “if the differences between the subject matter 

sought to be patented and the prior art are such that the 

subject matter as a whole would have been obvious at the 

time the invention was made to a person having ordinary 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 19

skill in the art.” 35 U.S.C. § 103(a) (2006).13 Obviousness 

is a question of law with underlying factual findings 

relating to the scope and content of the prior art; the 

differences between the claims and the prior art; the level 

of ordinary skill in the pertinent art; and any secondary 

considerations of non-obviousness. ZUP, LLC v. Nash 

Mfg., Inc., 896 F.3d 1365, 1371 (Fed. Cir. 2018) (citing 

Graham v. John Deere Co. of Kan. City, 383 U.S. 1, 17–18 

(1966)). The inherent teaching of a prior art reference is a 

question of fact. Par Pharm., Inc. v. TWI Pharm., Inc., 

773 F.3d 1186, 1194 (Fed. Cir. 2014). 

After a bench trial, we review a district court’s conclusions of law de novo and its findings of fact for clear error. 

Senju Pharm. Co. v. Lupin Ltd., 780 F.3d 1337, 1341 (Fed. 

Cir. 2015). A factual finding is clearly erroneous if the 

Court is left with “the definite and firm conviction that a 

mistake has been committed.” United States v. U.S. 

Gypsum Co., 333 U.S. 364, 395 (1948). 

On appeal, Teva disputes that the 40mg GA 3x/week

dosing regimen disclosed in the Copaxone patents would 

have been obvious to a person of skill in the art. Teva 

also appeals the invalidation of claim limitations in the 

’250 and ’413 patents relating to improved tolerability and 

reduced frequency of adverse effects, and the invalidation 

of the ’776 patent’s claims relating to reduced severity of 

 

13 Congress amended § 103 when it passed the 

Leahy-Smith America Invents Act (AIA). Pub. L. 

No. 112–29, § 3(c), 125 Stat. 284, 287 (2011). Because the 

applications that led to the patents at issue have never 

contained a claim having an effective filing date on or 

after March 16, 2013 (the effective date of the statutory 

changes enacted in 2011), or a reference under 35 U.S.C. 

§§ 120, 121, or 365(c) to any patent or application that 

ever contained such a claim, the pre-AIA § 103 applies. 

Id. § 3(n)(1), 125 Stat. at 293.
20 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

injection site reactions. Teva does not appeal on the 

objective indicia of nonobviousness. We address each 

argument in turn. 

A. 40mg GA 3x/week Dosing Regimen

Teva contends that the district court erred in finding 

the claimed 40mg GA 3x/week dosing regimen obvious. 

Specifically, Teva argues that the district court impermissibly relied on hindsight and an improper “obvious to try” 

analysis, and analyzed the obviousness of individual 

claim elements, rather than the invention as a whole. 

Teva further maintains that the district court’s decision is 

at odds with this court’s decision in In re Cyclobenzaprine 

Hydrochloride Extended-Release Capsule Patent Litigation, 676 F.3d 1063 (Fed. Cir. 2012). 

We first address Teva’s contention that the district 

court engaged in an impermissible “obvious to try” analysis. In KSR, the Supreme Court endorsed the use of an 

“obvious to try” analysis in certain cases:

When there is a design need or market pressure to 

solve a problem and there are a finite number of 

identified, predictable solutions, a person of ordinary skill has good reason to pursue the known 

options within his or her technical grasp. If this 

leads to the anticipated success, it is likely the 

product not of innovation but of ordinary skill and 

common sense. In that instance the fact that a 

combination was obvious to try might show that it 

was obvious under § 103.

KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). 

We have previously identified two categories of impermissible “obvious to try” analyses that run afoul of 

KSR and § 103: when what was “obvious to try” was (a) to 

vary all parameters or try every available option until one 

succeeds, where the prior art gave no indication of critical 

parameters and no direction as to which of many possibil-
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 21

ities is likely to be successful; or (b) to explore a new 

technology or general approach in a seemingly promising 

field of experimentation, where the prior art gave only 

general guidance as to the particular form or method of 

achieving the claimed invention. See In re Kubin, 561 

F.3d 1351, 1359 (Fed. Cir. 2009) (quoting In re O’Farrell, 

853 F.2d 894, 903 (Fed. Cir. 1988)). 

This case falls into neither of the two impermissible 

categories. Here, the prior art focused on two critical 

variables, dose size and injection frequency, and provided 

clear direction as to choices likely to be successful in 

reducing adverse side effects and increasing patient 

adherence. As of the priority date, only two GA dose sizes 

had been shown to be effective, safe, and well-tolerated: 

20mg and 40mg. Concerning frequency, the 1996 FDA 

SBOA, Flechter, and Khan 2008 all encouraged POSITAs 

to pursue a less frequent than daily dosing regimen; these 

references indicated that less frequent injections of GA 

were just as effective as daily injections, and less frequent 

injections improved patient adherence and reduced adverse reactions. The district court also properly relied on

Khan 2009 not as statutory prior art, but for the fact that 

POSITAs were interested in pursuing less frequent dosing 

regimens. In re Copaxone, 2017 WL 401943, at *14. 

Given this motivation, a POSITA had only a limited 

number of permutations of dose and frequency to explore 

that were not already disclosed in the prior art. Because 

a thrice-weekly 40mg injection would result in a total 

weekly dose very close to that in the already-approved

daily 20mg injection—120mg/week versus 140mg/week—

the district court found a POSITA would have had a 

reasonable expectation of success in pursuing the thriceweekly dose frequency in terms of effectiveness, patient 

adherence, and FDA approval. Id. at *19 (quoting Allergan, Inc. v. Sandoz Inc., 726 F.3d 1286, 1291 (Fed. Cir. 

2013) (“The potential for FDA approval also may properly 

be considered, as it was here, in determining whether one 
22 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

of ordinary skill would be motivated to develop a drug 

product and whether there was skepticism regarding the 

efficacy of such a product.”)). The district court gave 

appropriate weight to the testimony of Dr. Green regarding patient compliance with thrice-weekly administrations and the Rebif® regimen, noting that “[e]ven though 

Rebif® is a different MS drug with a different mechanism 

of action, . . . those in the art would still be motivated to 

try dosing GA three times a week based on the higher 

rates of patient adherence to the Rebif® therapy.” Id. at 

*20.

Teva faults the district court for “narrowing the universe” of possible GA regimens and using hindsight and 

the GALA protocol to reach its obviousness conclusion. 

Appellants’ Opening Br. 42 (arguing the district court 

limited a POSITA to “two dosing options (40mg and

20mg), two regimens (1x/week and 3x/week), and one form 

(injections)”). We disagree; the district court had ample 

evidence besides hindsight and the disclosures in GALA 

on which to find a thrice-weekly dosing regimen of 40mg 

GA obvious to try. See In re Copaxone, 2017 WL 401943, 

at *17–22. Although the universe of potential GA doses is 

theoretically unlimited, the universe of dosages in the 

prior art that had clinical support for being effective and 

safe consisted of only two doses: 20mg and 40mg. Even if 

there were multiple injection frequencies not yet tested in

the prior art—1x, 2x, 3x a week etc.—these still represent 

a limited number of discrete permutations. 

This is not a situation where the prior art gave no direction in how to reach a successful result; the prior art 

clearly indicated that less frequent doses should be explored (i.e., moving away from the daily, “7x/week” dose 

towards less frequent doses) and that higher doses, while 

maintaining the same weekly dose (i.e., moving from 

20mg daily to 40mg every other day), could increase 

efficacy while not affecting adverse reactions. Furthermore, the district court made factual findings specifically 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 23

in support of thrice-weekly injections. E.g., id. at *19 

(total weekly dose of 40mg GA 3x/week is very close to the 

total weekly dose for the approved daily 20mg GA regimen); id. at *20 (“[A] skilled artisan would be motivated 

to try regimens close in total milligrams per week to the 

regimens already approved by the FDA and known to be 

effective.”); id. (finding motivation to pursue a 3x/week 

regimen based on patient adherence rates in the Rebif®

therapy). And contrary to Teva’s argument that the court 

assumed without support that GA must be injected, the 

district court did not err in not considering other forms of 

GA. Evidence considered by the district court reveals that 

an oral version of Copaxone was proven to be ineffective 

by 2005. Id. at *23; J.A. 4016. We recognize that the 

prior art did not conclusively teach that a regimen of 

40mg GA 3x/week would be effective. However, 

“[c]onclusive proof of efficacy is not necessary to show 

obviousness. All that is required is a reasonable expectation of success.” Hoffmann-La Roche Inc. v. Apotex Inc., 

748 F.3d 1326, 1329, 1331 (Fed. Cir. 2014); see also In re 

O’Farrell, 853 F.2d at 903 (“Obviousness does not require 

absolute predictability of success.”). 

Nor do we find merit in Teva’s argument that the district court separately analyzed the 40mg dose limitation 

and the 3x/week limitation, without considering them 

together “except to conclude that the mash-up would be 

obvious to try.” Appellants’ Opening Br. 55. We note that 

the district court spent considerable time discussing why

the combination of a 40mg dose administered 3x/week 

would be obvious to try. See In re Copaxone, 2017 WL 

401943, at *19. And while “[t]he determination of obviousness is made with respect to the subject matter as a 

whole, not separate pieces of the claim,” SanofiSynthelabo v. Apotex, Inc., 550 F.3d 1075, 1086 (Fed. Cir. 

2008), this court has previously employed the same frequency-and-dosage-amount approach to obviousness used 

by the district court here. In Hoffmann-La Roche, 748 
24 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

F.3d at 1329, the court considered whether it would have 

been obvious at the time of invention to select a once a 

month oral dosing regimen of 150mg of ibandronate to 

treat osteoporosis. The court first discussed how the prior 

art taught that infrequent dosing, such as monthly dosing, was preferred. Id. at 1329–31. The court then separately discussed why a POSITA would have selected a 

150mg dose, before considering the limitations together 

and concluding that “[a]t the very least, the 150mg dose 

was obvious to try.” Id. at 1331–33. Teva makes no 

convincing argument why a similar approach is inappropriate here. 

Teva makes numerous challenges to factual findings 

by the district court, none of which we find persuasive. 

For instance, Teva argues that Cohen and FORTE teach 

away from using 40mg GA. The district court, however,

found that the decision to include 40mg in the later 

FORTE study indicates that Cohen did not teach away 

from trying 40mg. In re Copaxone, 2017 WL 401943, at

*15. The district court further noted although the FORTE 

study ostensibly “failed” at meeting its stated goal of 

establishing that 40mg/day was 30% more effective than 

20mg/day, FORTE still found that 40mg was equally 

effective with “no unexpected adverse effect,” and thus did 

not teach away. Id. We see no clear error in these findings. See Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d 

731, 738 (Fed. Cir. 2013) (“A reference does not teach 

away, however, if it merely expresses a general preference 

for an alternative invention but does not criticize, discredit, or otherwise discourage investigation into the invention claimed.”). Nor are we swayed by Teva’s arguments 

that the district court misread Khan 2008 and Caon in 

suggesting that patients in the 20mg/day group switched 

to 20mg every other day to reduce discomfort associated 

with daily injections. The district court cited extensive 

testimony clearly showing that POSITAs “were familiar 

with the adverse reactions, pain, and treatment adher-
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 25

ence problems associated with daily injections.”14 In re 

Copaxone, 2017 WL 401943, at *16. Given the evidence 

presented, the district court’s finding that patients wanted to switch to the every other day regimen to reduce 

discomfort associated with daily injections is a reasonable 

conclusion and not clearly erroneous. 

Teva further contends that the district court erred in 

relying on Flechter for its finding that a POSITA would 

have been motivated to pursue a less than daily dosing 

regimen. We do not reach this argument given that the 

district court correctly found similar motivations in other 

references, such as the SBOA and Khan 2008. Teva also 

takes issue with the district court’s use of the Pinchasi 

reference. Although the court noted that “Pinchasi is the 

closest prior art,” id. at *17, this observation is not improper; courts are required to determine “the scope and 

content of prior art” and the “differences between prior art 

and claims.” PAR Pharm., 773 F.3d at 1193 (emphasis 

added). Contrary to Teva’s assertion that the district 

court gave no reason why a person of ordinary skill would 

have started with Pinchasi, the district court in fact 

 

14 See, e.g., J.A. 4676–77 (Kolodny deposition, describing needle fatigue associated with Copaxone 

20mg/day); J.A. 4869 (Dr. Green, describing Khan 2008: 

“It reveals clear and obvious patient preference for an 

every-other-day dosing regimen when compared to a daily

dosing regimen given the option.”); J.A. 4857 (Dr. Green: 

“As we discussed, most of the adverse events associated 

with the use of glatiramer acetate, and in fact the most 

troubling set of adverse events had to do with injection 

site reactions or immediate post-injection reactions. Both 

of those are tied to injections. So if you reduce the frequency of injections, well, it’s clearly obvious that you 

would reduce the frequency of those injection site reactions or immediate post-injection reactions.”).
26 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

addressed Pinchasi fourth in its discussion on the thrice 

weekly dosing limitation, after the SBOA, Flechter, and 

Khan 2008/Caon references. See In re Copaxone, 2017 WL 

401943, at *15–17. Teva raises additional arguments 

regarding factual findings made by the district court, 

none of which we find persuasive. 

Finally, this court’s decision in In re Cyclobenzaprine, 

676 F.3d at 1063, does not warrant a different outcome. 

Teva argues that prior to the invention, higher doses of 

GA were not necessarily known to be more effective, GA’s 

pharmacokinetic and pharmacodynamic (“pk/pd”) profile 

was and remains unknown, GA’s mechanism of action is 

still unknown, and the cause of patient’s reactions to 

injections of GA is unknown. Teva contends that the 

unpredictable nature of GA categorically precludes the 

obvious-to-try analysis employed by the district court. 

Appellants’ Opening Br. 50. 

In Cyclobenzaprine, we held that bioequivalence alone 

could not establish obviousness because “skilled artisans 

could not predict whether any particular PK profile, 

including a bioequivalent one, would produce a therapeutically effective formulation.” 676 F.3d at 1070. The court 

applied traditional motivation and reasonableexpectation-of-success analysis, reasoning that “[w]hile it 

may have been obvious to experiment with the use of the 

same PK profile [from an immediate-release formulation] 

when contemplating an extended-release formulation, 

there [wa]s nothing to indicate that a skilled artisan 

would have had a reasonable expectation that such an

experiment would succeed in being therapeutically effective.” Id. In Cyclobenzaprine, there were no prior art 

clinical studies to suggest what would be a therapeutically effective formulation. 

We do not read Cyclobenzaprine as establishing a rigid rule categorically precluding obviousness findings 

without pk/pd data. Further, Cyclobenzaprine is distin-
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 27

guishable in that, there, the obviousness proof relied 

entirely on the bioequivalence of certain pharmacokinetic 

profiles. Bioequivalence is not argued here; instead, 

obviousness is proven through human clinical studies 

establishing the safety, efficacy, and tolerability of GA at 

doses and dose frequencies similar to the claimed regimen. In this case, the evidence shows that pk/pd data 

was largely irrelevant to the invention. Numerous clinical studies in the prior art describe GA and its effects on 

the human body. Although the precise mechanism of GA 

is not known, it is known to be immunomodulating—i.e., 

it changes the immune system—and is not necessarily 

measurable in the bloodstream and its levels are not 

indicative of efficacy. See In re Copaxone, 2017 WL 

401943, at *21–22; J.A. 3998–99, 4886–87. Testimony 

was given at trial that pharmacokinetic studies for drugs 

like GA are less appropriate than for small molecule 

drugs, such as those at issue in Cyclobenzaprine. J.A. 

4886–87. GA was also known to be “forgiving,” in that 

occasional missed doses would not reduce efficacy, and 

that fact gave POSITAs further confidence in eliminating 

one dose every two weeks. J.A. 4848–49; 4884–85; 4732. 

Higher doses were clinically shown to be at least as 

effective as lower doses; Cohen shows, at the very least, 

that 40mg is as effective and well-tolerated as 20mg, but 

with a more rapid onset of action. Finally, Teva itself, in 

its 1996 application to FDA, indicated that pharmacokinetic studies “would be of limited value.” J.A. 20689. 

In light of the foregoing, we hold that the 40mg GA 

3x/week regimen is obvious in light of the prior art, and 

find no clear error in the conclusion that a POSITA would 

be motivated to combine the 40mg GA dose, which had 

proven efficacy, with a 3x/week frequency, which was 

desirable because the prior art indicated that less frequent administration increased patient adherence while 

maintaining efficacy.
28 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

B. Improved Tolerability and Reduced 

Frequency Limitations

Claims 14, 16, and 17 of the ’250 patent and claim 7 of 

the ’413 patent require that the 40mg GA 3x/week regimen reduce the frequency of ISRs and IPIRs relative to 

the daily 20mg GA regimen. Claim 15 of the ’250 patent, 

on which claims 16 and 17 depend, requires that the 

claimed regimen improve tolerability as compared to the

daily 20mg regimen. 

Teva argues that the prior art did not lead POSITAs 

to expect improved tolerability and reduced frequency of 

injection reactions from the claimed regimen compared to 

20mg GA daily. We disagree, and find no clear error in 

the district court’s findings regarding Khan 2008, Caon, 

and Flechter, all of which demonstrate that improved 

tolerability and less frequent injection reactions were 

expected from the claimed less frequent regimen, as 

compared to 20mg daily. See In re Copaxone, 2017 WL 

401943, at *17–18. Caon, for example, disclosed that the 

frequency of a severe injection-site reaction, lipoatrophy, 

was “significantly less” for the every-other-day patient 

group than for the daily group. J.A. 20386. Pinchasi 

recognized that a 40mg GA dose resulted in increased 

efficacy “not accompanied by a corresponding increase of 

adverse reactions.” J.A. 20944. The court also relied 

upon testimony from Dr. Green that reducing the frequency of injections was expected to reduce the number of 

injection-related reactions. 

Teva finds fault with the district court’s reference to

“common sense” in its reliance on Dr. Green’s testimony. 

During trial, Appellees’ expert Dr. Green testified that a 

POSITA would expect reducing the frequency of injections 

to be associated with enhanced overall tolerability of the 

regimen. J.A. 4911. In its post-trial briefing, Teva argued that Dr. Green’s testimony was conclusory and 

unsupported by the prior art. The district court rejected 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 29

this characterization, noting that “it is simply common 

sense that if a patient experiences adverse reactions from 

an injection, reducing the number of injections they 

receive would reduce the number of times they have a 

reaction.” In re Copaxone, 2017 WL 401943, at *17. The 

district court went on to identify additional evidence in 

the record to support Dr. Green’s statement, including 

evidence in the Khan 2008/Caon and Flechter studies, 

and testimony from Dr. Wolinksy, Teva’s own expert, who 

testified that he had prescribed COPAXONE® 20mg for 

use every other day, off-label use, for his patients who 

were “doing extremely well on the drug but [were] having 

trouble with injection site problems.” Id. We see no error 

in what is essentially a credibility determination, where 

the district court credited Dr. Green’s expert testimony, 

supported by other evidence in the record, that a reduction in the number of injections would result in less 

frequent reactions. See J.A. 4857.

Teva also argues that the district court erred by relying on Teva’s GALA protocol. The district court did not 

use GALA as invalidating prior art, but instead as evidence of a POSITA’s motivations and expectations when

reading the prior art at the time of the invention. In re 

Copaxone, 2017 WL 401943, at *20. With respect to the 

sufficiency limitations, the district court used GALA only 

for that limited purpose, noting Teva’s statement to FDA 

that “one may certainly expect a reduction in the frequency of such reactions with this new dose regimen, further

enhancing subject adherence to treatment.” Id. at *18 

(emphasis added) (quoting J.A. 8267). The district court’s 

reliance on GALA merely as confirmation of how a 

POSITA would understand FORTE, which is prior art, is 

not erroneous. 

C. Reduced Severity Claims of the ’776 Patent

The asserted claims of the ’776 patent contain additional limitations requiring that the 40mg GA 3x/week
30 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

regimen “reduce[s] severity of injection site reactions” 

compared to a 20mg daily regimen. See, e.g., ’776 patent 

col. 17 ll. 37–54; col. 17 l. 65–col. 18 l. 22. The parties 

stipulated that “severity” means “the intensity of a patient’s ISRs and/or IPIRs.” J.A. 1994. “Severity” appears 

in the specification of the ’776 patent only once in connection with injection site reactions, in the definition of 

“tolerability,” which means “associated with the frequency 

and severity of post injection reactions and injection site 

reactions.” ’776 patent col. 7, ll. 37–42 (emphasis added). 

“Tolerability influences the period that a patient can 

follow GA treatment.” Id. 

After reviewing the prior art, the district court concluded that the ’776 patent’s claims directed to reducing 

the severity of injection site reactions would have been

obvious. In re Copaxone, 2017 WL 401943, at *22. The 

district court broadly relied on two different types of 

evidence in reaching this conclusion: evidence and testimony relating to lipoatrophy and evidence relating to 

tolerability. 

Concerning the evidence relating to lipoatrophy, the 

district court pointed to trial testimony establishing that 

lipoatrophy, the loss of subcutaneous fat at the injection 

site, is a severe ISR, and Caon’s disclosure that 

“[i]njection related lipoatrophy was significantly less” on 

the 20mg every other day regimen than on the daily 20mg 

regimen. Id. The court also relied on Teva’s expert Dr. 

Fox, who testified that “if there is a decrease in the frequency of lipoatrophy, there would, by definition, then 

also be a decrease in the severity of the adverse events.” 

Id. We agree with the district court that this evidence

“provides a reasonable expectation to those skilled in the 

art that reducing the number of injections per week may 

also reduce the severity of injection site reactions.” Id. 

In addition to the evidence regarding lipoatrophy, the 

district court also pointed to a press release issued by 
TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 31

Teva summarizing FORTE, which admitted that the 

40mg dose “maintained the favorable safety and tolerability profile of COPAXONE® 20mg,” and testimony from the 

named inventor, Dr. Klinger, that “if a 40 mg three-timesa-week regimen improves patient tolerability, then it 

inherently has to reduce the frequency and severity of 

injection site reactions.” Id. at *23. Citing Dr. Klinger’s 

testimony, the district court correctly concluded that “it 

follows that the FORTE study showed that administering 

40mg of GA daily to patients did not increase the frequency or severity of injection site reactions.” Id. 

Teva contends that the district court erroneously conflated frequency with severity, and that evidence of reduced frequency of ISRs cannot prove reduced severity of 

ISRs. While we agree that the two concepts are distinct, 

we conclude that the district court did not err. Frequency 

and severity of ISRs are not interchangeable, but Dr. 

Fox’s testimony established that, in certain instances, 

they are related: 

Q. Doctor, is severity the same thing as frequency?

A. No, they’re related, but they are separate 

topics.

Q. How do they relate to one another?

A. There, as I mentioned before . . . , there 

are some events like lipoatrophy that 

would be considered to be more severe. So 

if there is a decrease in the frequency of 

lipoatrophy, there would, by definition, 

then also be a decrease in the severity of 

the adverse events.

Q. So do you consider these two concepts to 

be mutually exclusive?

A. No, they are not. They are related.
32 TEVA PHARMACEUTICALS USA, INC v. SANDOZ INC. 

J.A. 5523.

Caon showed that reducing the frequency of injections 

from daily to every other day resulted in “significantly 

less lipoatrophy,” a severe ISR. This statement in Caon 

can be read as indicating either that lipoatrophy occurred 

less frequently with less frequent injections—which, 

according to Dr. Fox’s testimony, “by definition” means 

reduced severity—or the expression of the lipoatrophy 

itself was less severe. It was not unreasonable for the 

district court to conclude from this evidence that a 

POSITA would think it obvious that the 40mg GA 

3x/week regimen, with its less frequent injections, would 

result in reduced severity of at least one ISR, lipoatrophy, 

particularly given Dr. Fox’s testimony endorsing the 

same. See Hoffman–La Roche, 748 F.3d at 1331 (holding 

that prior art references need only demonstrate “a reasonable expectation of success,” not “conclusive proof of 

efficacy”). 

Teva also disputes the district court’s reliance on the 

FORTE press release. However, given that the findings 

made by the district court in reaching its obviousness 

conclusion, based on the other evidence relied on by the 

court, were not clearly erroneous, we do not reach this 

argument. 

CONCLUSION

In light of the foregoing, we conclude that the district 

court did not err in invalidating all asserted claims of the 

Copaxone patents as obvious. 

AFFIRMED

COSTS

No costs.