United States Court of Appeals 

for the Federal Circuit ______________________ 

YEDA RESEARCH AND DEVELOPMENT CO., 

LTD.,

Appellant

v.

MYLAN PHARMACEUTICALS INC., AMNEAL 

PHARMACEUTICALS LLC,

Appellees

______________________ 

2017-1594, 2017-1595, 2017-1596

______________________ 

Appeals from the United States Patent and 

Trademark Office, Patent Trial and Appeal Board in 

Nos. IPR2015-00643, IPR2015-00644, IPR2015-

00830, IPR2015-01976, IPR2015-01980, IPR2015-

01981.

______________________ 

Decided: October 12, 2018

______________________ 

 WILLIAM M. JAY, Goodwin Procter LLP, Washington, DC, argued for appellant. Also represented by 

WILLIAM G. JAMES, II; ELIZABETH HOLLAND, New 

York, NY; DARYL L. WIESEN, Boston, MA; JOHN C.

O'QUINN, Kirkland & Ellis LLP, Washington, DC;

LESLIE M. SCHMIDT, New York, NY. 
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 DAVID LEE ANSTAETT, Perkins Coie, LLP, Madison, WI, argued for appellees. Appellee Mylan Pharmaceuticals Inc. also represented by SHANNON 

BLOODWORTH, ROBERT SWANSON, BRANDON MICHAEL 

WHITE, Washington, DC; DAN L. BAGATELL, Hanover, 

NH; CHRISTINA JORDAN MCCULLOUGH, Seattle, WA.

 ANTHONY JAMES FITZPATRICK, Duane Morris LLP, 

Boston, MA, for appellee Amneal Pharmaceuticals 

LLC. Also represented by VINCENT CAPUANO,

CHRISTOPHER S. KROON; PATRICK GALLAGHER, Boca 

Raton, FL.

______________________ 

Before REYNA, BRYSON, and STOLL, Circuit Judges.

REYNA, Circuit Judge.

In this consolidated appeal, Appellant Yeda Research & Development Co., Ltd. challenges the Patent 

Trial and Appeal Board’s final written decisions 

finding the claims of U.S. Patent Nos. 8,232,250, 

8,399,413, and 8,969,302 unpatentable as obvious in 

three inter partes review proceedings. We affirm the 

Board’s decisions.1

 

1 In a companion case decided today, Teva 

Pharmaceuticals USA, Inc. v. Sandoz Inc., No. 17-

1575 (Fed. Cir. Oct. 12, 2018), 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 U.S. Patent 

Nos. 8,232,250, 8,399,413, 8,969,302, and 9,155,776. 
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BACKGROUND

I. Patents at Issue

Yeda Research and Development Co., Ltd. 

(“Yeda”) is the assignee of U.S. Patents Nos. 

8,232,250, 8,399,413, and 8,969,302 (the ’250, ’413, 

and ’302 patents, 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. See 

J.A. 267, 279, 291. The earliest priority date of the 

Copaxone patents is August 20, 2009. Id.

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 postinjection 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 
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COPAXONE® 20mg/mL, a regimen consisting of the 

daily injection of 20mg GA. Daily GA injections were 

known to subject patients to discomfort, including 

side effects in the form of ISRs and IPIRs. J.A. 6956. 

For analyzing the obviousness of the Copaxone 

patents, a key limitation of the 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 relapsingremitting 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.

Certain claims of the ’250 and ’413 patents further require improved tolerability and/or reduced 

frequency of injection reactions in the claimed regimen as compared to 20mg daily. ’250 patent col. 17 l. 

24–col. 18 l. 6; ’413 patent col. 16 ll. 51–54. 

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

doses. ’250 patent col. 16 ll. 35–45, col. 17 l. 25–col. 

18 l. 6, col. 18 ll. 19–26; ’413 patent col. 16 ll. 26–36, 

col. 18 ll. 1–13, col. 18 ll. 14–28; ’302 patent col. 17 ll. 

4–12. Claim 1 of the ’302 patent does not specify any 
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particular interval between doses, but dependent 

claims 4 and 5 limit injections to certain combinations 

of days of the week, all with at least one day between 

injections, and 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.” ’302 patent col. 16 ll. 

37–41, col. 16 ll. 47–58, col. 17 ll. 4–12. 

II. Prior Art References

The first clinical trial for using GA to treat multiple sclerosis was in 1987 by Dr. Bornstein et al. 

(“Bornstein”),2 which was followed later by a Teva 

Phase III clinical trial in 1995. Both Bornstein and 

the Phase III trial tested 20mg GA daily. J.A. 7279–

80, 7282–85, 6895–7235. The 20mg/day dose was 

selected without performing conventional optimaldose-finding studies. J.A. 7239. 

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. 7284. Participants 

in both Bornstein and the Phase III trial reported 

ISRs and IPIRs as side effects. J.A. 7284, 6934. 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. 6934. A Phase III 

trial reviewer made recommendations for future 

researchers to explore dose-response and doseranging studies, asking “Is 20 mg the optimum dose? 

Are daily injections necessary?” J.A. 6956. 

 

2 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).
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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”), the FDA recommended that Teva 

“evaluate the necessity of daily [GA] injections as 

opposed to more infrequent intermittent 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. 7146. 

A 2002 study by Flechter et al.3 (“Flechter”) evaluated the treatment of RRMS with 20mg of GA administered every other day. J.A. 7236–40. 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. 7240. Flechter also noted that patient dropout rates decreased 

when GA was administered every other day as opposed to daily. J.A. 7240 (“It should be stressed that 

the dropout rate was lower in the alternate-day group 

than in the daily-injection regime (39.7% versus 

60.3%, p < 0.01).”).

A prior art patent application, International Patent Application No. WO 2007/081975, Method of 

Treating Multiple Sclerosis (“Pinchasi”), was published in 2007. J.A. 6857–88. Pinchasi discloses a 

40mg GA, every other day dosing regimen for the 

treatment of RRMS. Pinchasi cites to the data from 

 

3 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).
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Cohen, another GA study, 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. 6876. 

III. State of the Art Reference

There is an additional reference relevant to this 

appeal, a 2009 study by Omar Khan4 (“Khan 2009”). 

J.A. 9331–32. Khan 2009 was published three weeks 

after August 20, 2009, the priority date of the asserted patents, and thus does not qualify as statutory 

prior art, but the study began two years earlier. J.A. 

9331–32. 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. 9331. 

Following the results of an earlier study, Khan 2008, 

showing 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 rater-blinded two-year 

study. J.A. 9331; see infra note 8. 

 

4 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).
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IV. Proceedings before the Board

Mylan Pharmaceuticals, Inc. (“Mylan”) filed petitions for inter partes review (“IPR”) in IPR2015-

00643, IPR2015-00644, and IPR2015-00830, challenging all claims of the ’250, ’413, and ’302 patents, 

respectively, on grounds pursuant to 35 U.S.C. §§ 102 

and 103. The Patent Trial and Appeal Board (the 

“Board”) instituted review of all claims of the Copaxone patents on two grounds: obviousness over 

Pinchasi in view of FDA’s 1996 SBOA, and over 

Pinchasi in view of Flechter.5 J.A. 644 (instituting 

 

5 In each of its Institution Decisions, the Board 

instituted on all claims but less than all grounds 

petitioned. See J.A. 644, 1720–21, 2710–11. The 

Supreme Court held in SAS Institute Inc. v. Iancu

that if the Director institutes IPR proceedings, the 

Board’s review must proceed “‘[i]n accordance with’ or 

‘in conformance to’ the petition,” including “‘each 

claim challenged’ and ‘the grounds on which the 

challenge to each claim is based.’” 138 S. Ct. 1348, 

1355–56 (2018) (alteration in original). Post-SAS, 

this court has held that remand to the Board can be 

appropriate to consider non-instituted grounds as well 

as non-instituted claims. See BioDelivery Scis. Int’l, 

Inc. v. Aquestive Therapeutics, Inc., 898 F.3d 1205, 

1208 (Fed. Cir. 2018) (collecting cases). 

At oral argument, Mylan stated that it did not 

seek remand on the grounds of partial institution in 

light of the Supreme Court’s decision in SAS. Oral 

Arg. at 6:12–7:05 (May 1, 2018), available at 

http://oralarguments.cafc.uscourts.gov/default.aspx?fl

=2017-1594.mp3. In the absence of a request for 

relief on the basis of SAS, we are not sua sponte 

obliged to act on the SAS error in this case. See PGS 
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IPR on the ’250 patent), 1720–21 (’413 patent), 2710–

11 (’302 patent). Subsequently, Amneal Pharmaceuticals LLC filed for each patent substantially identical 

petitions to those already filed by Mylan, and moved 

to join Mylan’s proceedings. The Board subsequently 

consolidated Amneal Pharmaceuticals’ petitions with 

those already filed by Mylan. J.A. 894–898, 1970–74, 

3489–95. Amneal Pharmaceuticals and Mylan are 

collectively referred to as “Petitioners.” 

The Board’s analysis of the independent claims 

was similar for all three patents. The Board first 

noted that Pinchasi discloses every limitation of the 

independent claims of the Copaxone patents, except 

for the dosing regimen of three doses per seven day 

period. The Board found that a person of ordinary 

skill in the art (“POSITA”) would have been motivated to use a 40mg dose, crediting the testimony of 

Petitioners’ expert, Dr. Green, who noted that 

Pinchasi demonstrated increased efficacy of 40mg GA

compared to 20mg with no significant difference in 

side effects, and citing Cohen,6 a study which con-

 

Geophysical AS v. Iancu, 891 F.3d 1354, 1362–63 

(Fed. Cir. 2018). 

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

Dose-Comparison Study of Glatiramer Acetate in 

Relapsing-Remitting MS, 68 Neurology 939, 939–44 

(2007). 

Cohen, published in 2007, was a “Randomized, 

double-blind, dose-comparison study of glatiramer 

acetate in relapsing-remitting MS.” J.A. 6889–94. 

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. 6889. Cohen also noted that the onset of action 
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cluded that daily administration of 40mg GA was 

effective, safe, and well tolerated. In reaching this 

finding, the Board also found that FORTE,7 a phase 

III clinical trial comparing 40mg GA and 20mg GA, 

would not have taught away from using 40mg because 

it did not criticize, discredit, or discourage the 40mg 

GA dose. 

The Board next considered whether there was a 

motivation to modify Pinchasi’s 40mg every other day 

 

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

J.A. 6894. ISRs were the most frequent adverse event 

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

6892–93. IPIRs occurred more frequently in the 40mg

group than the 20mg group. J.A. 6892–93. Cohen 

thus concluded that the overall safety and side effect 

profile of the 40mg GA dose was “similar” to the 20mg 

dose, but “was associated with a greater incidence of 

certain adverse effects.” J.A. 6894. 7 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);

J.A. 11532–40.

The FORTE study evaluated the safety, tolerability, and efficacy of 40mg GA compared to 20mg GA, 

and concluded that there are “[n]o significant differences in efficacy measures between GA 20mg and GA 

40mg,” and that the 40mg dose has a “[g]ood safety 

and tolerability profile” with “no unexpected adverse 

effect with the high dose.” J.A 11532–40. FORTE 

also confirmed a finding from an earlier study, Cohen, 

that the 40mg dose provides an earlier onset of action. 

J.A. 11540. 
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regimen. The Board noted that the difference between the challenged claims (6 doses over 2 weeks) 

and Pinchasi (7 doses over 2 weeks) was only one less 

injection every two weeks. The Board then found 

motivation to eliminate one injection every other 

week to increase patient compliance, relying in part 

on Petitioners’ expert Dr. Green, who testified that 

decreasing the frequency of injections helps with 

patient adherence to a treatment regimen, and FDA’s 

1996 SBOA, which recommended that the necessity of 

daily injections, as opposed to less frequent administration, be evaluated. The Board further relied on 

other prior art references, including Flechter, Khan 

2008,8 and Caon,9 which showed that alternate-day 

 

8 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 RelapsingRemitting Multiple Sclerosis, 14 Multiple Sclerosis 

S296, S296 (2008). 

This 2008 study by Omar Khan and others (“Khan 

2008”) compared the effect of daily versus every other 

day administration of 20mg GA subcutaneous injections for the treatment of RRMS. J.A. 7252. The 

study abstract noted that although the recommended 

dose for treating RRMS is daily 20mg GA injections, 

“the optimal dose remains unknown” and there is 

“considerable interest in alternate dosing regimens of 

GA” because daily injections “can be challenging for 

long-term patient compliance.” J.A. 7252. 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. 7252. Additionally, after the first two years elapsed, patients in 

each group were given the option to continue or 
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dosing of 20mg was safe, well-tolerated, as effective as 

daily 20mg, reduced injection reactions, and that 

patients in the daily-injection group preferred less

frequent dosing. The Board also found Khan 2009 

probative of the fact that POSITAs were motivated to 

investigate dosing regimens of GA with fewer injections to improve patient compliance. 

Having found a motivation in the prior art to pursue a less frequent dosing regimen, the Board found 

that a POSITA would have a reasonable expectation 

of success in administering 40mg GA three times per 

week in light of testimony that GA was “a forgiving 

drug,” and that combining a 40mg dose with threetimes-a-week administration produced a weekly dose 

virtually identical to the FDA-approved regimen of 

20mg GA daily. The Board then concluded that, in 

light of the evidence presented, a POSITA would have 

had a reason to modify Pinchasi’s dosing regimen of 

40mg GA every other day to 40mg GA 3x/week, thus 

 

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. 

9 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). 

The Caon reference, 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. 7253. 
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rendering the claimed 40mg 3x/week limitation 

obvious. 

The Board also considered additional limitations

for each patent, including limitations requiring improved tolerability, reduced frequency of adverse 

reactions, and specific injection schedules, and also 

found them obvious in light of the prior art. With 

regard to the objective indicia of nonobviousness, the 

Board concluded that the objective indicia were

insufficient to overcome the primary findings of 

obviousness. And finally, for similar but less detailed 

reasons as for Pinchasi/SBOA, the Board concluded 

that the claims are unpatentable over the combination of Pinchasi and Flechter. 

Yeda moved for rehearing. The Board issued revised final written decisions that reached the same 

results. Mylan Pharm. Inc. v. Yeda Research & Dev. 

Co., IPR2015-00643, No. 90, at 40 (P.T.A.B. Dec. 2, 

2016) (“’250 patent FWD”); Mylan Pharm. Inc. v. Yeda 

Research & Dev. Co., IPR2015-00644, No. 91, at 41

(P.T.A.B. Dec. 2, 2016) (“’413 patent FWD”); Mylan 

Pharm. Inc. v. Yeda Research & Dev. Co., IPR2015-

00830, No. 85, at 37 (P.T.A.B. Dec. 2, 2016) (“’302

patent FWD”). Yeda appeals the Board’s reliance on 

Khan 2009 and its obviousness decisions. We have 

jurisdiction pursuant to 28 U.S.C. § 1295(a)(4)(A). 

DISCUSSION

We review decisions of the Board under the 

standard of the Administrative Procedure Act (APA). 

Novartis AG v. Torrent Pharm. Ltd., 853 F.3d 1316, 

1323 (Fed. Cir. 2017). We hold unlawful and set aside 

the actions of the Board if they are “not in accordance 

with law” or “unsupported by substantial evidence.” 5 

U.S.C. § 706. 
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I. Khan 2009

Yeda contends that its due process rights and the 

APA were violated because it did not have notice of, 

and an opportunity to respond to, Khan 2009. Yeda 

also argues that the Board violated 35 U.S.C. § 311(b) 

by relying on Khan 2009, which does not qualify as 

statutory prior art. 

Khan 2009 was first introduced as part of the reply declaration of Dr. Green, Petitioners’ expert. In 

its patent owner response, Yeda had argued that, as 

of the priority date, a POSITA would have believed 

that more frequent than daily administrations of GA 

would have been the best way to enhance efficacy. 

J.A. 758. In his reply declaration, Dr. Green responded that “[n]umerous prior art references suggested 

further investigation of less frequent dosing regimens 

prior to 2009.” J.A. 9529 ¶ 29. After citing other 

prior art references, namely the SBOA, Flechter, 

Khan 2008, and Caon, Dr. Green discussed Khan 

2009, noting that “before the priority date, POSAs 

had completed a clinical trial investigating 20 mg 

administered twice weekly, for a total weekly dose of 

only 40 mg.” J.A. 9532 ¶ 32. Dr. Green concluded 

that “the Khan 2009 reference demonstrates that—

counter to what Patent Owner claims—POSAs were 

motivated before the priority date to explore less 

frequent alternative dosing regimens.” J.A. 9532–33 

¶ 32. 

We first consider whether Yeda’s due process 

rights were violated. “[T]he introduction of new 

evidence in the course of the trial is to be expected in 

inter partes review trial proceedings and, as long as

the opposing party is given notice of the evidence and 

an opportunity to respond to it, the introduction of 

such evidence is perfectly permissible under the 

APA.” Genzyme Therapeutic Prods. LP v. Biomarin 
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Pharm. Inc., 825 F.3d 1360, 1366 (Fed. Cir. 2016). 

Here, Yeda received notice of Khan 2009 in Dr. 

Green’s reply declaration, attached to Petitioners’ 

reply. Yeda deposed Dr. Green after receiving his 

reply declaration; he discussed Khan 2009 in that 

deposition and was questioned about it. J.A. 11164–

65, 11176–79. Yeda also moved to exclude Khan 2009 

as irrelevant, which the Board denied. J.A. 1153–54; 

see also ’250 patent FWD, at 35–36. Yeda could have, 

but did not, address Khan 2009 at the oral hearing or 

seek leave to file a surreply to substantively respond 

to Khan 2009, as encouraged by our precedent. See 

Genzyme, 825 F.3d at 1368. 

Based on this record, Yeda received proper notice 

of and an opportunity to respond to Khan 2009—an 

opportunity Yeda took advantage of when it moved to 

exclude the study. But Yeda contends that it had no 

notice that the Board “might rely extensively” on 

Khan 2009 and make it “an essential part of its 

obviousness analysis.” Appellant’s Reply Br. 27. 

Thus, although Yeda frames its argument as being 

about due process, it really only challenges the 

Board’s use of Khan 2009.

In its final written decisions, the Board acknowledged that Khan 2009 does not qualify as statutory 

prior art, but because the study began two years 

before the priority date of the Copaxone patents, the 

Board concluded that Khan 2009 is “probative of the 

fact that those skilled in the art were motivated to 

investigate dosing regimens of GA with fewer injections to improve patient compliance.” ’250 patent 

FWD, at 15; see also ’413 patent FWD, at 17; ’302 

patent FWD, at 16. With one exception, discussed 

below, the Board’s use of Khan 2009 falls squarely 

within this stated purpose of providing evidence of the 

motivation of a POSITA to explore less frequent 

dosing regimens as of the priority date. See ’250 
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patent FWD, at 15, 18, 36; ’413 patent FWD, at 16–17, 

19; ’302 patent FWD, at 16, 18. 

Yeda contends that the Board relied on Khan 

2009 to supplement gaps in the prior art in violation 

of 35 U.S.C. § 311(b). Section 311(b) provides that the 

Board may consider the patentability of challenged 

claims “only on the basis of prior art consisting of 

patents or printed publications.” We note that, before 

the Board, Yeda only sought to exclude Khan 2009 on 

the ground that it was irrelevant, and thus its argument regarding § 311(b) is arguably waived. J.A. 

1153–54. However, § 311(b) is unrelated to the question of whether the Board’s reliance on Khan 2009 

was proper. While Khan 2009 indisputably does not 

qualify as prior art, § 311(b) only addresses prior art 

and is silent on the question of other evidence. The 

question before us, therefore, is whether the Board 

may consider non-prior art evidence, such as Khan 

2009, in considering the knowledge, motivations, and 

expectations of a POSITA regarding the prior art.

Based on the statutory scheme, the PTO’s own 

regulations, and prior Board decisions, the Board can 

rely on evidence other than just prior art. The statute 

permits IPR petitioners to rely on evidence beyond 

the asserted prior art. Section 312(a)(3) of Title 35 

specifies that a petition should include both “copies of 

patents and printed publications that the petitioner 

relies upon,” and “affidavits or declarations of supporting evidence and opinions.” So do the regulations. 

See 37 C.F.R. § 42.104(b) (describing the content of 

the petition, including both “the patents or printed 

publications relied upon for each ground,” and “supporting evidence relied upon to support the challenge”). The Board has recognized that non-prior art 

evidence of what was known “cannot be applied, 

independently, as teachings separately combinable” 

with other prior art, but “can be relied on for their 
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proper supporting roles, e.g., indicating the level of 

ordinary skill in the art, what certain terms would 

mean to one with ordinary skill in the art, and how 

one with ordinary skill in the art would have understood a prior art disclosure.” Dominion Dealer Sols., 

LLC v. AutoAlert, Inc., IPR2014-00684, 2014 WL 

5035359, at *5 (P.T.A.B. Oct. 6, 2014). 

In this regard, Dr. Green’s reliance on Khan 2009 

is permissible, as it supports and explains his position 

that a POSITA would have thought less frequent 

dosing worthy of investigation as of the priority date. 

We note that Dr. Green also relied on multiple prior 

art references—namely the SBOA, Flechter, Khan 

2008, and Caon—in support of this opinion. J.A. 9532 

¶ 32. With one exception, the Board’s use of Khan 

2009 is in line with Dr. Green’s narrow interpretation, and does not constitute error. See ’250 patent 

FWD, at 15 (“Khan 2009 is probative of the fact that 

those skilled in the art were motivated to investigate 

dosing regimens of GA with fewer injections to improve patient compliance.”); id. (“Khan 2009 concludes: ‘This study provides further evidence that GA 

administered less frequently than daily may be as 

efficacious and better tolerated than GA administered 

daily.’” (emphasis added)); id. at 18 (mentioning Khan 

2009 as one of many studies of less frequent dosing, 

undermining the opinion of Yeda’s expert that a 

POSA would want to administer more than once 

daily)10; id. at 35 (“[Khan 2009] reflects that, before 

 

10 We recognize that, in this instance, the Board 

included Khan 2009 at the end of a string citation 

listing “[n]umerous prior art references studying less 

frequent dosing.” ’250 patent FWD, at 18 (emphasis 

added); ’413 patent FWD, at 18 (same); ’302 patent 

FWD, at 18 (same). Having considered the Board’s 
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the ’250 patent invention, those skilled in the art 

were motivated to investigate dosing regimens with 

less frequent than daily injections”); ’413 patent FWD, 

at 16–17 (same as ’250 patent FWD, at 15); ’302 

patent FWD, at 16 (same).

In one instance, the Board relied on Khan 2009 

for a different purpose, namely, in deciding whether a 

POSITA would have had a reasonable expectation of 

success of a thrice-weekly regimen. ’250 patent FWD, 

at 21 (“[A]s discussed above, nearly two years before 

the priority date of the ’250 patent, Khan 2009 commenced its study on 20 mg GA administered twice-aweek, further evincing that an ordinary artisan would 

have had a reasonable expectation of success in 

pursuing a 40 mg, three-times-weekly GA dosing 

regimen.”). To the extent that this reliance was error, 

we conclude that it was harmless error. Khan 2009 

was the last piece of evidence in a lengthy analysis, in 

which the Board also relied on Flechter, Khan 2008, 

Caon, Pinchasi, and testimony from Dr. Green in 

finding a POSITA would have had a reasonable 

expectation of success in the claimed regimen. Even 

if the Board’s reliance on Khan 2009 was improper, it 

is harmless error because substantial evidence otherwise supports the Board’s conclusion. 

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 

 

decision as a whole, and in particular the portion 

discussing how Khan 2009 is not statutory prior art, 

’250 patent FWD, at 15–16, we conclude that the 

Board’s characterization of Khan 2009 as being prior 

art was a simple oversight, constituting harmless 

error. 
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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 skill in the art.” 35 U.S.C. § 103(a) 

(2006).11 

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 nonobviousness. 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). 

On appeal, Yeda disputes the Board’s conclusion 

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. Yeda also appeals the 

invalidation of the ’250 patent’s claims relating to 

increased tolerability, the ’413 patent’s claims relating to decreased frequency of side effects, and the ’302 

patent’s claims relating to specific-day dosing regi-

 

11 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 preAIA § 103 applies. Id. § 3(n)(1), 125 Stat. at 293.
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mens. Yeda does not appeal on the objective indicia of 

nonobviousness. We address each argument in turn.

A. 40mg GA 3x/week Dosing Regimen

Yeda contends that the Board erred as a matter of 

law in finding the claimed 40mg GA 3x/week dosing

regimen obvious. Specifically, Yeda claims that, in 

finding that a POSITA had a reasonable expectation 

of success, the Board disregarded inherent uncertainties associated with GA. Yeda also argues that the 

Board engaged in hindsight bias, considered the 

obviousness of individual claim elements separately 

rather than the claimed invention as a whole, and 

failed to account for the “minimum effective dose” 

principle in considering what the prior art taught 

POSITAs. 

We first consider Yeda’s argument that the Board 

erred as a matter of law in finding a reasonable 

expectation of success of the claimed regimen by 

disregarding certain uncertainties associated with 

GA, namely the fact that GA’s pharmacokinetic and 

pharmacodynamic (“pk/pd”) profile, mechanism of 

action, optimal dose, and active species are all unknown. Yeda contends that this case is “indistinguishable” from In re Cyclobenzaprine Hydrochloride 

Extended-Release Capsule Patent Litigation, 676 F.3d 

1063 (Fed. Cir. 2012), and argues that a reasonable 

expectation of success is categorically impossible in 

the absence of a pk/pd profile. Appellant’s Opening 

Br. 38–39. 

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 

reasonable-expectation-of-success analysis, reasoning 
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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 determinations without pk/pd data. There, the court’s

error was relying on bioequivalence alone, without 

any evidence in the prior art teaching or suggesting a 

therapeutically effective formulation to one skilled in 

the art, such as pk/pd data. Here, however, the Board 

committed no such error; the record is replete with 

prior art that would have taught or suggested a 

therapeutically effective formulation to a POSITA. 

The Board pointed to clinical studies that taught the 

effectiveness of 20mg daily (Copaxone® 20mg), 20mg 

every other day (Flechter, Khan 2008, Caon), and 

40mg daily (Cohen, FORTE), and the Pinchasi application, which suggested that 40mg every other day

would be therapeutically effective. See ’250 patent

FWD, at 12–14, 20; ’413 patent FWD, at 16–18, 21–22;

’302 patent FWD, at 15–16, 20, 29–30. 

Further, the evidence considered by the Board reveals that pk/pd data was largely irrelevant to the 

invention. The Board credited testimony from Petitioners’ expert Dr. Green, who testified that POSITAs 

considered GA to be a “forgiving drug,” with a wide 

range of likely efficacious doses. E.g., ’250 patent

FWD, at 16–17. Yeda itself argued to the Board that 

the “plasma half-life of GA . . . is irrelevant to the 

pharmaceutical effect of the drug,” and that “GA 
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cannot be measured in the plasma and no PK/PD 

correlation is even possible.” J.A. 772 (citation omitted). In light of Yeda’s own representations to the 

Board that “the standard small molecule textbook 

pharmacokinetic principles . . . cannot be used to 

predict the therapeutic effects of GA,” id., we decline 

to find error in the Board’s obviousness decision 

simply because it lacked pk/pd data. 

Yeda makes challenges to the Board’s factual 

findings concerning reasonable expectation of success, 

none of which we find persuasive. Although Yeda 

contests the Board’s finding that GA is a “forgiving 

drug,” leading POSITAs to have a reasonable expectation in administering 40mg GA 3x/week, this conclusion is supported by substantial evidence, including 

Dr. Green’s expert testimony. ’250 patent FWD, at 

18–19. The Board’s finding that the uncertainty 

around GA’s mechanism of action would motivate a 

POSITA to stick to dosing regimens with existing 

clinical support, such as 20mg and 40mg, is supported 

by substantial evidence from Dr. Green. Id. at 18. 

Because “the expectation of success need only be 

reasonable, not absolute,” we find no error in these 

findings. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 

1364 (Fed. Cir. 2007). 

Next, Yeda argues that the Board improperly considered the claimed dose amount and the claimed 

frequency separately, “manipulat[ing] both parameters at the same time,” without finding an affirmative 

reason to combine them. Appellant’s Opening Br. 45, 

48. We disagree. The Board’s analysis began with 

Pinchasi, which it found disclosed every claim element except the requirement to inject 40mg GA 

3x/week, as opposed to every other day. ’250 patent 

FWD, at 10. The only difference between the prior art 

and the claimed invention was, therefore, the difference between thrice weekly and every other day 
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administration. We do not read the Board’s decision 

as manipulating both parameters simultaneously, but 

rather, as considering the claimed regimen in the 

context of the prior art regimens, both in terms of 

dose size and frequency. 

Nor do we find, as Yeda urges, that the Board improperly engaged in hindsight by starting its analysis 

with Pinchasi as the closest prior art reference. 

Appellant’s Reply Br. 3–4. At the outset, we note that 

this argument was raised by Yeda for the first time in 

its reply brief, and thus is waived. And while we have 

previously cautioned against relying on hindsight bias 

in selecting a lead prior art reference after the fact, 

we find no hindsight in the Board’s analysis. See, e.g., 

WBIP, LLC v. Kohler Co., 829 F.3d 1317, 1337 (Fed. 

Cir. 2016) (“The real question is whether that skilled 

artisan would have plucked one reference out of the 

sea of prior art . . . .”); Ortho-McNeil Pharm., Inc. v. 

Mylan Labs., Inc., 520 F.3d 1358, 1364 (Fed. Cir. 

2008). Here, far from a “sea of prior art,” the references before the Board presented a finite and known 

pool of dose and frequency options easily traversed to 

show obviousness. See KSR Int’l Co. v. Teleflex Inc., 

550 U.S. 398, 421 (2007) (“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.”). The dosages in the prior art that had clinical 

support for being effective and safe consisted of only 

two: 20mg and 40mg. The prior art disclosed both 

daily and every other day administration, and the

Board found a motivation for both less frequent 

injections and a thrice-weekly regimen specifically. 

’250 patent FWD, at 13–16. Given the small field of 

prior art references with clinical support, we find no 

clear error in the Board’s finding that the “[p]otent 
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and promising activity in the prior art” would have 

encouraged a POSITA to traverse the experimental 

options to produce this invention. See Daiichi Sankyo 

Co. v. Matrix Labs., Ltd., 619 F.3d 1346, 1354 (Fed. 

Cir. 2010); Ortho-McNeil, 520 F.3d at 1365. 

The Board thoroughly addressed Yeda’s arguments to the contrary, namely, that a POSITA would 

not use 40mg of GA on any dosing schedule, would not 

have used a 3x/week dosing regimen, and that there 

would not have been a reasonable expectation of 

success of 40mg GA 3x/week being therapeutically 

effective. See ’250 patent FWD, at 11. In so doing, the 

Board found that a POSITA would have been motivated to use 40mg, id. at 11–13, that a POSITA would 

have been motivated to use a 3x/week dosing regimen, 

id. at 13–16, and that a POSITA would have had a 

reasonable expectation of success in using 40mg GA 

3x/week to be therapeutically effective, id. at 16–22. 

Given these findings, and given that the difference 

between the claimed invention and the prior art is 

only one dose per two week period, the Board did not 

need to articulate a further motivation to combine the 

40mg dose and the 3x/week schedule. 

Yeda makes other arguments attacking the 

Board’s fact finding regarding motivation to combine. 

For instance, Yeda points to Cohen, which reported a 

slightly higher rate of adverse effects in 40mg compared to 20mg doses, as evidence that a POSITA 

would not have been motivated to inject 40mg doses. 

However, the Board also considered the FORTE 

study, which noted that the higher 40mg dose “maintained the favorable safety and tolerability profile” of 

20mg GA. ’250 patent FWD, at 12–13. Yeda also 

contests Dr. Green’s testimony relating to Rebif®, 

another RRMS drug that uses a 3x/week dosing 

regimen. Yeda argues that it was improper to rely on 

Rebif as proof of efficacy, in that GA and Rebif have 
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different mechanisms of action. However, Dr. Green 

did not rely on Rebif to demonstrate GA’s efficacy, but 

rather for the point that patients adhered well to 

Rebif’s regimen of thrice-weekly injections, suggesting 

that a 3x/week GA injection regimen would improve 

patient compliance. Id. at 16; J.A. 6628–29 ¶ 53. We 

have considered Yeda’s other arguments to this effect 

and find them unpersuasive. 

Finally, Yeda argues that the Board erred in failing to consider the “minimum effective dose” principle. According to Petitioners’ expert, Dr. Peroutka, 

the minimum effective dose is the lowest dose of a 

drug that will achieve a desired effect, and in general, 

is preferred unless higher doses lead to increased 

efficacy with an acceptable amount of side effects. 

Mylan Pharm. Inc. v. Yeda Research & Dev. Co., 

IPR2015-00643, Ex. 1003, ¶ 44 (P.T.A.B. Mar. 3, 

2015) (“Peroutka Decl.”). Based on this principle, 

Yeda argues that following the FORTE study—which 

concluded that the GA 40 mg dose did not demonstrate increased efficacy in reducing the relapse rate, 

J.A. 11308—a POSITA “would have had no motivation to pursue a 40mg dose, on any schedule.” Appellant’s Opening Br. 52. Yeda argues that the Board’s 

failure to address minimum effective dose is legal 

error.

Although the Board did not address the minimum 

effective dose principle by name in its decisions, these 

omissions do not constitute reversible error. First, as 

an initial matter, the Board is “not require[d] . . . to 

address every argument raised by a party or explain 

every possible reason supporting its conclusion.” 

Synopsys, Inc. v. Mentor Graphics Corp., 814 F.3d 

1309, 1322 (Fed. Cir. 2016), overruled on other 

grounds by Aqua Prods., Inc. v. Matal, 872 F.3d 1290, 

1296 n.1 (Fed. Cir. 2017) (en banc). And while agencies are required to address “important aspect[s] of 
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the problem,” Motor Vehicle Mfrs. Ass’n of U.S., Inc. v. 

State Farm Mut. Auto Ins. Co., 463 U.S. 29, 43 (1983),

here, minimum effective dose is mentioned only 

briefly in Yeda’s patent owner responses, in a single 

paragraph discussing Petitioners’ expert, Dr. Peroutka. See J.A. 752, 1828, 3365. As we have said numerous times, failure to explicitly discuss every 

fleeting reference or minor argument does not alone 

establish that the Board did not consider it. See 

Novartis, 853 F.3d at 1328 (citing cases). 

Second, the record on appeal indicates that the 

Board considered the minimum effective dose principle. At oral argument, the Board discussed the effect 

of less frequent dosing on dose size. Yeda’s counsel 

argued that, under the minimum effective dose principle, a POSITA would have “no reason to go to 

40[mg].” J.A. 1352. In response, the Board queried 

whether, if a POSITA would have been motivated to 

move to less frequent dosing, “doesn’t it open up the 

world of possibilities again that we can start with 20 

and 40 and then start all over and figure out which is 

the proper less frequent dosing?” J.A. 1352; see also 

J.A. 1353–54. Further, Yeda’s reliance on the minimum effective dose principle in its response was in 

support of its position that FORTE taught away from 

using 40mg. See Mylan Pharm. Inc. v. Yeda Research 

& Dev. Co., IPR2015-00643, No. 26, at 17–19 

(P.T.A.B. Nov. 20, 2015) (patent owner response) 

(discussing minimum effective dose under the subheading: “After the FORTE trial, a POSA would not 

have used a 40 mg dose of GA to treat MS”). The 

Board expressly addressed whether FORTE taught 

away from a 40mg dose in the final written decisions. 

See, e.g., ’250 patent FWD, at 13 (“Because nothing in 

FORTE criticizes, discredits, or discourages the use of 

40 mg of GA, we determine that FORTE does not 

teach away from the use of 40 mg of GA.”). 
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In light of the foregoing, we conclude that substantial evidence supports the Board’s reliance on the 

clinical data and its conclusion that a POSITA would 

be motivated to combine Pinchasi’s 40mg every other 

day dose with a less frequent dosing regimen, such as 

3x/week, and would have had a reasonable expectation of success in therapeutic effectiveness and patient compliance. Accordingly, we affirm the Board’s 

finding that the 40mg GA 3x/week regimen is obvious 

in light of the prior art. 

B. Increased Tolerability Claims

Claim 15 of the ’250 patent, from which claims 

16–18 depend, requires that the claimed 40mg GA 

3x/week regimen improve tolerability as compared to 

the daily 20mg regimen. ’250 patent col. 17 l. 24–col. 

18 l. 6. In the ’250 patent, “tolerability” “relates to 

the level of discomfort associated with GA treatment,” 

and “is associated with the frequency and severity of 

post injection reactions and injection site reactions.” 

Id. col. 7 ll. 33–37.

Yeda argues that the Board did not sufficiently 

address the tolerability limitations of claims 15–18 of 

the ’250 patent. We disagree, and find that substantial evidence supports the Board’s finding that a 

POSITA, considering the prior art teachings as a 

whole, had a reason to switch from 20mg GA daily to 

a 40mg GA 3x/week regimen, and would have known 

that doing so would increase the tolerability of the GA 

regimen as compared to 20mg GA daily. ’250 patent 

FWD, at 25. The Board pointed to Khan 2008 and 

Caon, which reported that 20mg every other day had 

increased tolerability over 20mg daily, including 

significantly less lipoatrophy, as showing that every 

other day dosing decreases injection-related side 

effects. Id. at 24–25. 
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Yeda now claims that the Board disregarded other 

prior art references that contradict Khan 2008 and 

Caon, including Flechter and FORTE. Concerning 

Flechter, the Board concluded that Flechter does not 

show that every other day administration is less 

tolerable than daily administration. Id. at 33–34. 

This conclusion was based on the Board’s rejection of 

testimony of Yeda’s expert, Dr. Ziemssen, who compared Flechter with another study, Meiner, on the 

grounds that cross-study comparisons are not reliable. 

Having concluded elsewhere that Flechter makes no 

statement as to tolerability, there would be no reason 

for the Board to cite Flechter with respect to claims 

15 to 18. And although FORTE was not cited in this 

section, the Board earlier in the decision noted 

FORTE’s conclusion that the 40mg dose “maintained 

the favorable safety and tolerability profile of 

COPAXONE® 20mg.” Id. at 13. Because the Board 

found that an increased dose does not decrease tolerability and the evidence reveals that a POSITA would 

believe that decreased injection frequency would 

increase tolerability, we conclude that the Board’s 

decision is supported by substantial evidence and 

legally proper.

C. Reduced Frequency of ISRs and 

IPIRs Claims

Claim 7 of the ’413 patent depends on claim 1, 

and further requires that the claimed method reduce

the frequency of an IPIR or ISR relative to daily 

administration of 20 mg GA. ’413 patent col. 16 ll. 

51–54. The Board found all dependent claims of the 

’413 patent unpatentable as obvious in light of 

Pinchasi and the 1996 SBOA. ’413 patent FWD, at 

23–24. 

In finding claim 7 obvious, the Board adopted the 

reasoning in Dr. Green’s declaration discussing how 
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decreasing the frequency of injections decreases the 

frequency of reactions relative to 20mg daily. Id. at 

23 (citing Mylan Pharm. Inc. v. Yeda Research & Dev. 

Co., IPR2015-00644, Ex. 1004 ¶ 109 (Feb. 7, 2015) (“It 

would have been and is common sense that reducing 

the frequency of administration from 20 mg daily

would in turn decrease the frequency of injection site 

reactions and immediate post injection reactions.”)). 

The Board also considered, and rejected, Yeda’s 

argument that 40mg doses are associated with more 

injection site reactions, on the grounds that it was not 

supported by the prior art. Id. at 24. Moreover, in 

the paragraph discussing claim 7, the Board cited 

portions of Petitioners’ reply—which in turn relied on 

Khan 2008, Caon, Dr. Green’s testimony, and other 

evidence—discussing how less frequent dosing would 

increase tolerability by reducing ISRs. Id. (citing J.A. 

2117–20). 

Yeda faults the Board for not considering all of its 

arguments. “[W]e will uphold a decision of less than 

ideal clarity if the agency’s path may reasonably be 

discerned.” In re NuVasive, Inc., 842 F.3d 1376, 1383 

(Fed. Cir. 2016) (quoting Bowman Transp., Inc. v. 

Ark.-Best Freight Sys., Inc., 419 U.S. 281, 286 (1974)). 

Having reviewed the Board’s decision, we conclude 

that while the Board’s analysis regarding claim 7 is 

concise, it is supported by substantial evidence. 

We are further convinced that the Board did not 

err because the record is replete with Board findings 

that increased tolerability claims would be obvious. 

As in the ’250 patent, the ’413 patent defines tolerability to be associated with the frequency of ISRs and 

IPIRs. ’413 patent col. 7 ll. 28–32. And although 

claim 7 of the ’413 patent does not itself reference 

tolerability, the parties and the Board referred to 

claim 7 as concerning tolerability. See, e.g., J.A. 138 

(Board’s decision granting-in-part request for rehear-
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ing) (“We note that none of the claims, other than 

claim 7, recite any limitation regarding tolerability.”); 

J.A. 1371 (statement of Yeda’s counsel at oral argument) (“One set of claims have to do with the increased tolerability of the GA treatment, and what

I’m talking about now is ’250, claims 14 to 17, and 

’413, claim 7.” (emphasis added)). In light of the 

substantive overlap between the reduced frequency 

and the increased tolerability claims, and given our 

earlier holding that the Board did not err in finding 

the increased tolerability claims obvious, we affirm 

the Board’s finding regarding claim 7 of the ’413 

patent. See supra Discussion, section II.B. 

D. Specific Dosing Regimen Claims

Claims 4, 5, and 11 of the ’302 patent each specify 

a particular three-day schedule in a seven-day period 

on which GA injections are administered. For example, claim 4 of the ’302 patent requires that the three 

subcutaneous 40mg GA injections “are on three days 

each week selected from the group consisting of day 1, 

day 3 and day 5; day 1, day 3 and day 6; day 1, day 4 

and day 6; day 2, day 4 and day 6; day 2, day 4 and 

day 7; [day] 2, day 5 and day 7; and day 3, day 5 and 

day 7.” ’302 patent col. 16 ll. 47–52. 

In response to Yeda’s argument that Pinchasi did 

not disclose all elements of these claims, the Board 

explained that the question is not whether Pinchasi 

discloses administering 40mg of GA three times 

weekly to meet the further limitations of claims 4, 5, 

and 11, but rather, “we must look at what the prior 

art teaches as a whole.” ’302 patent FWD, at 22. In 

considering these specific dosing regimen claims, the 

Board adopted the reasoning of Dr. Green in his 

expert declaration, namely that “[c]hoosing specific 

days each week, such as Monday, Wednesday, and 

Friday, for example” is obvious, and that “choosing 
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specific days for injections increases patient adherence and compliance.” J.A. 6654 ¶ 107. The Board 

also adopted reasoning from the petition, including 

that “[t]he three specific days of the week are a matter of patient and physician choice from a limited 

number of possibilities.” J.A. 2590.

We see no error in the Board’s finding. “[A] court 

can take account of the inferences and creative steps 

that a person of ordinary skill in the art would employ.” KSR, 550 U.S. at 418. Having already found 

the 40mg GA 3x/week limitation obvious, merely 

identifying the specific days for the thrice-weekly 

regimen is the natural application of the method, with 

a finite number of identified and predictable solutions, and requires not innovation but ordinary skill 

and common sense. See id. at 421.

CONCLUSION

In light of the foregoing, we conclude that the 

Board did not err in finding all claims of the Copaxone patents unpatentable as obvious. 

AFFIRMED

COSTS

No costs.