NOTE: This disposition is nonprecedential.

United States Court of Appeals 

for the Federal Circuit ______________________ 

GENZYME CORPORATION, SANOFI-AVENTIS U.S., 

LLC,

Plaintiffs-Appellees

v.

DR. REDDY'S LABORATORIES, LTD., DR. 

REDDY'S LABORATORIES, INC., TEVA 

PHARMACEUTICALS USA INC,

Defendants-Appellants

______________________ 

2016-2206, 2016-2207

______________________ 

Appeals from the United States District Court for the 

District of Delaware in Nos. 1:13-cv-01506-GMS, 1:13-cv01508-GMS, Judge Gregory M. Sleet.

______________________ 

Decided: December 18, 2017

______________________ 

 PAUL HENRY BERGHOFF, McDonnell, Boehnen, Hulbert & Berghoff, LLP, Chicago, IL, argued for plaintiffsappellees. Also represented by ALISON JAMEEN BALDWIN,

PAULA FRITSCH, JAMES LEE LOVSIN, JEREMY E. NOE, KURT 

WILLIAM RHODE; JEFFREY B. BOVE, Ratner Prestia, Wilmington, DE.
2 GENZYME CORPORATION v. DR. REDDY’S LABORATORIES, LTD. 

 MARTIN B. PAVANE, Cozen O’Connor, New York, NY, 

argued for all defendants-appellants. Defendantsappellants Dr. Reddy’s Laboratories, Ltd., Dr. Reddy’s 

Laboratories, Inc. also represented by MARILYN NEIMAN. 

 ELAINE BLAIS, Goodwin Procter LLP, Boston, MA, for 

defendant-appellant Teva Pharmaceuticals USA Inc. Also 

represented by EMILY L. RAPALINO; MICHAEL B. COTTLER,

NATASHA ELISE DAUGHTREY, ALEXANDRA D. VALENTI, New 

York, NY; WILLIAM M. JAY, Washington, DC.

______________________ 

Before MOORE, PLAGER, and CHEN, Circuit Judges.

CHEN, Circuit Judge. 

This consolidated set of appeals arises from a HatchWaxman action brought by Genzyme Corporation and 

Sanofi-Aventis U.S. LLC (collectively, Genzyme) against 

Dr. Reddy’s Laboratories, Ltd., Dr. Reddy’s Laboratories, 

Inc., and Teva Pharmaceuticals USA, Inc. (collectively, 

DRL). After a bench trial, the district court held, inter 

alia, that DRL failed to prove that claim 19 of U.S. Patent 

No. 7,897,590 (the ’590 Patent) is invalid for obviousness. 

We affirm. 

BACKGROUND

Stem cells are immature blood cells that reside in the 

bone marrow, where they can develop into mature blood 

cells, including white blood cells. Although stem cells are 

normally present in the blood in very small numbers, they 

can be “mobilized” from the bone marrow into the peripheral blood under certain conditions. 

I. The ’590 Patent

Genzyme developed a method for mobilizing and harvesting stem cells by sequentially administering two drug 

products. Specifically, the ’590 Patent makes use of a 
GENZYME CORPORATION v. DR. REDDY'S LABORATORIES, LTD. 3

regimen comprising a combination of granulocyte-colony 

stimulating factor (G-CSF) and plerixafor1 to increase the 

number of stem cells in the blood for collection. See ’590 

Patent, col. 3 l. 34–col. 4 l. 27. 

Under normal conditions, stem cells are anchored to 

the bone marrow at least in part through a bond between 

a particular receptor (CXCR-4) located on the stem cell 

and a protein (SDF-1) produced in the bone marrow. See

id. at col. 2 ll. 31–63. Plerixafor releases the stem cells 

into the bloodstream by disrupting that bond. 

Claim 19 of the ’590 Patent is the only claim at issue 

in this set of appeals. It recites a “method to obtain 

progenitor and/or stem cells” by (1) administering G-CSF 

to a subject; (2) administering plerixafor or a pharmaceutically acceptable salt thereof to the subject, in an amount 

effective to mobilize the progenitor and/or stem cells; and 

(3) harvesting the progenitor and/or stem cells. See ’590 

Patent, claim 19. 

II. Procedural History

Following a four-day bench trial before the district 

court, the parties submitted proposed findings of facts and 

conclusions of law. J.A. 63. DRL filed a motion under 

Fed. R. Civ. P. 52(c) for a judgment on partial findings on 

its affirmative defense and counterclaim asserting invalidity of claim 19 of the ’590 Patent. J.A. 64. 

The district court concluded that claim 19 was not invalid for obviousness and entered a final judgment enjoining DRL from commercially manufacturing, using, 

offering for sale, selling, or importing its generic products 

before expiration of the ’590 Patent. J.A. 1–30. 

 

1 Plerixafor (also known as JM-3100 and AMD3100) is the active chemical ingredient in Mozobil® and 

Genzyme’s ANDA products. See J.A. 6-9.
4 GENZYME CORPORATION v. DR. REDDY’S LABORATORIES, LTD. 

DRL timely appealed. J.A. 2334–37. We have jurisdiction under 28 U.S.C. § 1295(a)(1). 

DISCUSSION

The determination of obviousness is a legal conclusion

based on underlying facts. Allergan, Inc. v. Sandoz Inc., 

726 F.3d 1286, 1290–91 (Fed. Cir. 2013). After a bench 

trial, we review the district court’s factual findings for 

clear error and its conclusions of law de novo. Honeywell 

Int’l, Inc. v. United States, 609 F.3d 1292, 1297 (Fed. Cir.

2010). 

A patent claim is invalid for obviousness if “the differences between the claimed invention and the prior art are 

such that the claimed invention as a whole would have 

been obvious before the effective filing date of the claimed

invention to a person having ordinary skill in the art to

which the claimed invention pertains.” 35 U.S.C. § 103.

The “underlying factual considerations in an obviousness analysis include the scope and content of the prior 

art, the differences between the prior art and the claimed

invention, the level of ordinary skill in the art, and any 

relevant secondary considerations[,]” which include

“commercial success, long-felt but unsolved needs, failure

of others, and unexpected results.” Allergan, 726 F.3d at

1290–91 (citations omitted). Patent invalidity must be 

established by clear and convincing evidence. Microsoft

Corp. v. i4i Ltd. P’ship, 564 U.S. 91, 95, 131 S.Ct., 180 

L.Ed.2d 131 (2011).

As part of its obviousness challenge, DRL presented, 

inter alia, the following prior art: (1) Hendrix et al., 

Pharmacokinetics and Safety of AMD-3100, a Novel 

Antagonist of the CXCR-4 Chemokine Receptor, in Human 

Volunteers, 44:6 ANTIMICRO. AGTS. AND CHEMO. 1667–73 

(Jun. 2000) (Hendrix); (2) International Patent Application Publication No. WO 00/45814 (WO ’814); and (3) U.S. 

Patent No. 5,824,304 (the ’304 Patent). 
GENZYME CORPORATION v. DR. REDDY'S LABORATORIES, LTD. 5

I. Hendrix in combination with the ’304 Patent

DRL’s first § 103 challenge to the ’590 Patent is based 

on a combination of Hendrix and the ’304 Patent. Hendrix focused on evaluating the safety and pharmacology of 

plerixafor for treating HIV. J.A. 18. The authors of 

Hendrix reported an increase in white blood cells (WBCs) 

in the peripheral blood of all subjects after an administration of plerixafor. J.A. 12286. To explain this phenomenon, Hendrix observed the following: (1) Chemokines such 

as stromal cell-derived factor 1 (SDF-1) are produced 

locally in tissue, and their primary purpose is the trafficking and chemoattraction of lymphocytes; (2) the CXCR-4 

cell receptor is widely expressed;2 and (3) in experiments, 

plerixafor has been shown to “completely inhibit” binding 

of SDF-1 to CXCR-4. J.A. 12288. From these observations, Hendrix hypothesized that “binding of [plerixafor] 

to CXCR4 may inhibit the chemotactic effects of SDF-1α, 

causing release of WBCs from the endothelium and/or 

stem cells from bone marrow.” Id. 

The ’304 Patent teaches a method for increasing the 

number of stem cells in the peripheral blood by administering a blocking agent of VLA-4 antigens. The VLA-4 

block agent releases stem cells from the marrow to the 

peripheral blood by inhibiting the VLA-4 receptor on stem 

cells, thereby disrupting the tether between the receptor 

and its natural ligand, VCAM-1, found in the marrow. 

J.A. 2617–20; J.A. 12819; J.A. 12834. The ’304 Patent 

also teaches that G-CSF mobilized stem cells from the 

marrow to the peripheral blood by stimulating production 

of such cells in the marrow. J.A. 12834; J.A. 12836. 

Thus, by administering G-CSF and a VLA-4 blocking 

agent, mobilization is achieved. Id.

 

2 The CXCR-4 receptor is not unique to stem cells 

and can be on found on blood cells that are more mature. 

J.A. 2591.
6 GENZYME CORPORATION v. DR. REDDY’S LABORATORIES, LTD. 

DRL argues that the only difference between the 

claimed invention and the ’304 Patent is that the ’304 

Patent does not teach that the blocking agent can be 

plerixafor. But that would have been obvious, DRL 

argues, because Hendrix expressly suggested that 

plerixafor could function as a blocking agent for releasing 

stem cells from the marrow. 

The district court, however, found that Hendrix was 

not analogous art. J.A. 19–20. Whereas Hendrix focused 

on HIV treatment, the ’590 Patent focused on mobilizing 

stem cells for subsequent harvest and transplantation. 

Although the parties agreed that a person of ordinary 

skill in the art would have been aware of the need for a 

better stem cell mobilizing regimen, they disputed the 

likelihood that CXCR-4 (and using plerixafor as a CXCR-4 

antagonist) would become the object of research as a stem 

cell mobilizing agent. J.A. 18. The Court found that 

Defendants failed to show that a POSA would have pursued CXCR-4 over the field of cytokines and other possible 

stem cell mobilizers. J.A. 19. Without a specific focus on 

CXCR-4, the district court concluded that Hendrix would 

not have been reasonably pertinent to an ordinarilyskilled artisan focused on harvesting stem cells. Id. 

But even if Hendrix were deemed analogous art, the 

district court found that Hendrix would not have rendered 

claim 19 obvious. J.A. 20. The district court expressly 

rejected DRL’s position that it was “reasonably predictable in October 2000 that plerixafor would mobilize stem 

cells in sufficient numbers for harvesting and tranplantation.” J.A. 23. It also found that the evidence established 

a “history of failure in the field[.]” Id. 

While we have carefully considered the findings below 

and all of the parties’ arguments, we discuss principally 

the parties’ dispute over whether a person of skill in the 

art would have had a “reasonable expectation of success” 

in achieving the claimed invention by combining the prior 
GENZYME CORPORATION v. DR. REDDY'S LABORATORIES, LTD. 7

art. See Insite Vision Inc. v. Sandoz Inc., 783 F.3d 853, 

859 (Fed. Cir. 2015). “Whether a person of ordinary skill 

in the art would narrow the research focus to lead to the 

invention depends on the facts.” Id. at 860. Here, the 

district court found that a skilled artisan would not have 

had a reasonable expectation of success that plerixafor 

would mobilize stem cells. DRL has not shown that this 

determination was clearly erroneous. 

As noted, the ’304 Patent discloses that blocking the 

receptor VLA-4 with an antibody can result in mobilization of stem cells. J.A. 12834. To render the ’590 Patent

obvious, DRL combines this teaching with the use of 

plerixafor in Hendrix to argue that plerixafor can mobilize 

stem cells in the same way – i.e., by blocking CXCR-4, a 

different receptor, and disrupting the connection between 

CXCR-4 and SDF-1. 

The record, however, shows that CXCR-4 is in a completely different family of receptors than VLA-4. The ’304 

Patent never mentions CXCR-4, SDF-1, or plerixafor. It 

explains that the stem cell mobilization seen with VLA-4 

antagonists is “due to the specific blocking of VLA-4.” 

J.A. 12839. Further, DRL’s expert testified that a typical 

stem cell has around one hundred different types of 

receptors on its surface. J.A. 2679; 3261–62. The district 

court, noting the parties’ arguments and evidence, agreed 

with Genzyme that “the ’304 Patent’s discussion of VLA-4 

antibody blocking agents would not have rendered obvious claim 19, which covers CXCR-1 and not VLA-4.” J.A. 

21–22. There is no evidence that VLA-4 localizes stem 

cells in the marrow like the CXCR-4/SDF-1 bond, and no 

expectation that CXCR-4 and VLA-4 would behave similarly concerning mobilization. 

Although Hendrix hypothesized in an isolated sentence, without explanation, that plerixafor may cause 

stem cell mobilization, the rest of the seven-page article

focused on the elevation of WBC counts. Hendrix men-
8 GENZYME CORPORATION v. DR. REDDY’S LABORATORIES, LTD. 

tioned SDF-1 and its function of attracting lymphocytes, 

not stem cells. J.A. 12288. The discussion of CXCR-4 

being widely expressed was also directed to different 

types of WBCs rather than stem cells. Id. A skilled 

artisan would have recognized that Hendrix never tested 

for the presence of stem cells. J.A. 2877–78. The primary 

speculation in Hendrix for the phenomenon associated 

with elevated WBC counts was “demargination,” which 

refers to the release of WBCs from the endothelium. J.A.

2882. This emphasis on demargination is consistent with 

how an independent group of contemporary researchers 

perceived Hendrix. J.A. 13245. 

The district court’s finding that stem cell mobilization 

was highly unpredictable at the time of the invention also 

runs counter to an expectation of success. J.A. 23. In 

particular, there was great uncertainty about the role of 

SDF-1 or CXCR-4, if any, in the process of stem cell 

mobilization. J.A. 27. CXCR-4 antagonists were only 

studied in the HIV field, and there was a history of failure 

resulting from the investigation of more than a dozen 

candidates in the search for a better stem cell mobilization agent. J.A. 23. No one had ever mobilized stem cells 

with any CXCR-4 antagonist, let alone plerixafor.3 And 

there were many different cytokines and growth factors 

that were the subject of research for a skilled artisan

looking for a better stem cell mobilizer. The district court

 

3 DRL’s reliance on various secondary references 

(Aiuti, Mohle, Peled, and Ma) to establish the CXCR4/SDF-1 connection does not call for a different result in 

this case. Some of the references focused on the migration

of stem cells to the marrow, the opposite of mobilization of 

stem cells from the bone marrow into the peripheral 

blood. None of the papers report any in vivo experiments 

demonstrating that manipulation of either CXCR-4 or 

SDF-1 mobilizes stem cells. 
GENZYME CORPORATION v. DR. REDDY'S LABORATORIES, LTD. 9

weighed all evidence and assessed the credibility of witnesses. Its view that there was no reasonable expectation 

of success, based on the evidence presented at trial on a 

combination of Hendrix and the ’304 Patent, was not 

clearly erroneous.

II. WO ’814 in combination with the ’304 Patent

DRL’s alternative basis for invalidating the ’590 Patent is the combination of the WO ’814 Patent and the 

’304 Patent. Like Hendrix, “WO ’814 does not disclose 

information about using plerixafor to mobilize stem cells, 

but instead reveals the relationship between plerixafor 

and white blood cell elevation.” J.A. 22. As the district 

court explained, DRL’s argument that WO ’814 would 

have led a skilled artisan to use plerixafor to mobilize 

stem cells “depends upon the assumption that a [person of

ordinary skill in the art] would have known that white 

blood cells are a proxy for stem cells.” J.A. 22. But the 

record included ample evidence showing that an increased 

WBC count did not necessarily correlate to stem cell 

mobilization. J.A. 2906–9; J.A. 2870. 

Ultimately, the deficiency regarding the combination 

of Hendrix and the ’304 Patent also undercuts the combination of WO ’814 and the ’304 Patent. As noted, sufficient evidence supports the district court’s finding of a

lack of a reasonable expectation of success. It is also 

significant that a gap exists between using plerixafor to 

enhance WBC counts and for stem cell mobilization. DRL 

attempted to bridge that gap with the ’304 Patent by 

analogizing plerixafor’s antagonism of CXCR-4 to the 

stem cell-mobilizing effect of the ’304 Patent’s anti-VLA-4 

antibody. But the district court considered and reasonably rejected this analogy. J.A. 22 (“[T]he court is not 

persuaded . . . that the ’304 Patent would teach a POSA to 

use plerixafor as a CXCR-4 blocking agent, simply because plerixafor is an agent like an anti-VLA-4 blocking 

agent.”). 
10 GENZYME CORPORATION v. DR. REDDY’S LABORATORIES, LTD. 

CONCLUSION

After reviewing the record surrounding the prior art 

and analyzing the arguments of the parties, we conclude 

that the district court’s factual conclusions regarding an 

insufficient reasonable expectation of success were not 

clearly erroneous. That evidence is sufficient to uphold 

the district court’s determination against the arguments 

DRL has presented for reversal, and we need not review 

the district court’s analysis of secondary considerations

that, if sound, could only further undermine DRL’s argument for obviousness. 

We have considered DRL’s remaining arguments but 

find them unpersuasive. For the foregoing reasons, we 

affirm the district court’s holding that the ’590 Patent is 

not invalid. 

AFFIRMED