NOTE: This disposition is nonprecedential.

United States Court of Appeals 

for the Federal Circuit ______________________ 

UNIVERSITY OF MARYLAND BIOTECHNOLOGY 

INSTITUTE,

Appellant

v.

PRESENS PRECISION SENSING GMBH,

Cross-Appellant

______________________ 

2016-2745, 2017-1057

______________________ 

Appeals from the United States Patent and Trademark Office, Patent Trial and Appeal Board in No. 

95/000,615.

______________________ 

Decided: November 3, 2017

______________________ 

 RENE A. VAZQUEZ, Sinergia Technology Law Group, 

PLLC, Leesburg, VA, argued for appellant.

 MICHAEL STEVEN CULVER, Millen, White, Zelano & 

Branigan PC, Arlington, VA, argued for cross-appellant.

______________________ 

Before LOURIE, O’MALLEY, and TARANTO, Circuit Judges.
2 UNIV. OF MD. BIOTECH v. PRESENS PRECISION SENSING GMBH

LOURIE, Circuit Judge. 

The University of Maryland Biotechnology Institute 

(“Maryland”) appeals from the inter partes reexamination 

decision of the United States Patent and Trademark 

Office (“PTO”) Patent Trial and Appeal Board (“the 

Board”) affirming the examiner’s rejection of claims 1, 3–

6, 9–11, 13–16, 19, and 20 (“the claims”) of U.S. Patent 

6,673,532 (“’532 patent”) as obvious under 35 U.S.C. § 103 

(2006).1 Presens Precision Sensing GmbH v. Univ. of Md. 

Biotechnology Inst., No. 2015-006297, 2015 WL 9581532 

(P.T.A.B. Dec. 29, 2015) (“Decision”), reh’g denied, 

(P.T.A.B. July 29, 2016). Because the Board did not err in 

holding the claims invalid as obvious, we affirm. 

BACKGROUND

Maryland owns the ’532 patent, which covers methods 

of measuring parameters in cell culture. Cell culture is a 

widely used technique to cultivate cells in vitro. Parameters such as glucose, pH, and carbon dioxide and oxygen 

levels affect the viability of cell cultures. Consequently, 

monitoring such parameters is important in optimizing 

cell culture conditions. See, e.g., ’532 patent col. 1 ll. 47–

64. 

The ’532 patent discloses an optical method of monitoring various cell culture parameters. The method 

implements four key components: (1) a cultivation vessel; 

(2) a sensor; (3) an excitation source; and (4) a detector. 

Id. col. 5 ll. 1–5. Cells are grown in a cultivation vessel 

that includes sensors which selectively bind to certain 

analytes. The sensors are light-sensitive, so when an 

 

1 Because the application of the ’532 patent was filed 

before March 16, 2013, the pre-Leahy-Smith America 

Invents Act version of § 103 applies. See Pub L. No. 112-

29, 125 Stat. 284 (2011); 35 U.S.C. § 103 (2006). 
UNIV. OF MD. BIOTECH v. PRESENS PRECISION SENSING GMBH 3

excitation source such as a light-emitting diode (“LED”)

shines on the sensors, the sensors emit light corresponding to the concentration of the relevant analytes. Detectors such as photomultiplier tubes then measure the light 

emitted by the sensors. Id. col. 4 l. 57–col. 5 l. 10. 

Appellee Presens Precision Sensing (“Presens”) petitioned for inter partes reexamination of the ’532 patent, 

which the PTO granted. Claim 1 of the ’532 patent, as 

amended during reexamination, is representative and 

reads as follows: 

1. A method of measuring at least two cultivation 

parameters in a cell culture, comprising:

(a) providing a cultivation vessel, wherein the cultivation vessel comprises, walls that define a single continuous volume or a non-planar surface 

that defines a single continuous volume, and at 

least two types of optical chemical sensors positioned within the single continuous volume;

(b) placing a continuous culture medium within 

the single continuous volume of the cultivation 

vessel such that the continuous culture medium is 

in contact with at least one of the walls that define the single continuous volume of the cultivation vessel or the non-planar surface that defines 

the single continuous volume of the cultivation 

vessel, wherein the optical chemical sensors are 

positioned such that they are in contact with the 

continuous culture medium;

(c) establishing a cell culture in the continuous 

culture medium;

(d) exciting the optical chemical sensors to generate emission and/or light absorption, wherein the 

optical chemical sensors are excited using at least 

one excitation source per optical chemical sensor; 
4 UNIV. OF MD. BIOTECH v. PRESENS PRECISION SENSING GMBH

(e) detecting the emission and/or absorption generated by the at least two optical chemical sensors 

in (d) by at least one detector for each type of optical chemical sensor used; and

(f) analyzing the detected emission and/or absorption detected in (c) to assess the at least two cultivation parameters measured.

J.A. 646–47, 1005.

The examiner rejected the claims as, inter alia, obvious over Shabbir B. Bambot et al., Potential Applications 

of Lifetime-Based, Phase-Modulation Fluorimetry in 

Bioprocess and Clinical Monitoring, 13 Trends in Biotechnology 106 (1995) (“Bambot”), and Bernhard H. Weigl 

et al., Optical Triple Sensor for Measuring pH, Oxygen 

and Carbon Dioxide, 32 J. Biotechnology 127 (1994) 

(“Weigl”). 

Bambot described optical methods of measuring analytes such as glucose, pH, and oxygen and carbon dioxide 

levels in bioreactors. The methods implemented the same 

set of components as the ’532 patent. Various cultivation 

vessels housed sensors excitable by several types of excitation sources, and the sensors’ emissions could be measured by several different detectors. 

Similarly, Weigl described a triple sensor device for 

measuring pH, oxygen, and carbon dioxide in a cultivation 

vessel. However, in Weigl the sensors were located in 

individual flow-through units outside the cultivation 

vessel. Each unit had a dedicated excitation source and 

detector. Given the teachings of Bambot and Weigl in 

combination, the examiner concluded that the claims of 

the ’532 patent would have been obvious over the references at the time the invention was made. 

The Board affirmed the examiner’s obviousness rejection. The Board agreed that Bambot taught placing 

sensors inside a cultivation vessel, and also disclosed 
UNIV. OF MD. BIOTECH v. PRESENS PRECISION SENSING GMBH 5

multiple types of sensors, detectors, and excitation 

sources. Furthermore, the Board found that Weigl taught 

monitoring multiple parameters using a separate detector 

and excitation source for each type of sensor. Consequently, the Board concluded that “it would have been 

obvious to arrange more than one sensor inside a cultivation vessel and [use] the light excitation and detection 

means described in Bambot for each one.” Decision, 2015 

WL 9581532, at *13.

Maryland appealed, and we have jurisdiction under

28 U.S.C. § 1295(a)(4)(A). 

DISCUSSION

Our review of a Board decision is limited. In re Baxter 

Int’l, Inc. 678 F.3d 1357, 1361 (Fed. Cir. 2012). We review 

the Board’s legal determinations de novo, In re Elsner, 

381 F.3d 1125, 1127 (Fed. Cir. 2004), but we review the 

Board’s factual findings underlying those determinations 

for substantial evidence, In re Gartside, 203 F.3d 1305, 

1316 (Fed. Cir. 2000). A finding is supported by substantial evidence if a reasonable mind might accept the evidence as adequate to support the finding. Consol. Edison 

Co. v. NLRB, 305 U.S. 197, 229 (1938). 

The legal conclusion of obviousness turns on the familiar Graham factors, including the teachings of the 

prior art and the differences between those teachings and 

the claimed invention. Graham v. John Deere Co., 383 

U.S. 1, 17–18 (1966). In assessing obviousness, we must 

“look with care at a patent application that claims as 

innovation the combination of two known devices according to their established functions.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). However, we also 

exercise caution before holding a claimed invention obvious when combining references would violate the principle of operation of the modified reference. See In re 

Mouttet, 686 F.3d 1322, 1332 (Fed. Cir. 2012) (discussing 

In re Ratti, 270 F.2d 810, 813 (CCPA 1959)). This is 
6 UNIV. OF MD. BIOTECH v. PRESENS PRECISION SENSING GMBH

because a person of ordinary skill generally would not be 

motivated to modify a reference by contradicting its basic 

teachings, see id., or by making it “inoperable for its 

intended purpose,” In re Gordon, 733 F.2d 900, 902 (Fed. 

Cir. 1984). 

Maryland argues that because Weigl’s sensors are positioned outside the cultivation vessel, Weigl cannot be 

modified in view of Bambot without “completely 

chang[ing] the fundamental principle of operation of 

Weigl.” Appellant’s Br. 20. When such a modification of a 

reference is necessary, Maryland contends, it does not 

support a determination of obviousness under Ratti, 270 

F.2d at 813. 

Presens responds that Maryland misinterprets the 

Board’s reliance on Weigl. According to Presens, the 

Board did not conclude that claim 1 was obvious by modifying the configuration of Weigl’s sensors; rather, the 

Board, citing the examiner’s finding, relied on Weigl for 

measuring multiple parameters and using a separate 

detector and excitation source for each sensor. Presens 

argues that the Board’s obviousness holding was based on 

Bambot’s sensor configuration, not Weigl’s, so Maryland’s 

application of Ratti is misplaced. 

We agree with Presens that Maryland misapplies Ratti. A person of ordinary skill is “not an automaton,” KSR, 

550 U.S. at 421, limited to physically combining references, see Mouttet, 686 F.3d at 1332 (citing In re Etter, 

756 F.2d 852, 859 (Fed. Cir. 1985) (en banc)). Even 

assuming that extra-vessel sensors are a “basic principle” 

of Weigl, Ratti, 270 F.2d at 813, that principle is independent of Weigl’s pertinence to the Board’s obviousness 

determination. The Board found that Weigl taught 

measuring multiple parameters and using a separate 

detector and excitation source for each sensor. Substantial evidence supports that finding. Figure 1 of Weigl 

depicts a separate detector and excitation source for each 
UNIV. OF MD. BIOTECH v. PRESENS PRECISION SENSING GMBH 7

sensor membrane. J.A. 366. Weigl described each flowthrough unit as “independent,” id., and implemented

different types of excitation sources and detectors for 

different sensors, J.A. 367, 369.

The Board’s findings regarding Weigl are consistent 

with Bambot’s principle of operation, as substantial 

evidence also supports the Board’s findings that Bambot

taught intra-vessel sensors in addition to multiple types 

of sensors, detectors, and excitation sources, and that 

Bambot suggested measuring multiple analytes in cultivation vessels. For example, Bambot disclosed oxygen 

sensors embedded within cultivation vessels, J.A. 130, 

and stated that the oxygen sensors “performed satisfactorily in a bioreactor environment,” J.A. 128–29. Bambot 

also described other optical sensors for pH, carbon dioxide, and glucose, multiple types of excitation sources such 

as blue LEDs and red laser diodes, and multiple detectors 

such as photomultiplier tubes and semiconductor detectors. J.A. 127–30. In its conclusion, Bambot indicated 

that measurement of “oxygen (and other analytes)” in 

cultivation vessels was feasible, J.A. 132, and proposed a 

separate “multianalyte sensing system,” J.A. 131. 

Unlike in Ratti, we cannot say here that the “suggested combination of references would require a substantial 

reconstruction and redesign of the elements shown” in 

Bambot, or a “change in [its] basic principles.” 270 F.2d 

at 813. Rather, Bambot and Weigl taught every element 

of the claimed invention and the combination of the 

references accords with their teachings. “The combination of familiar elements according to known methods is 

likely to be obvious when it does no more than yield 

predictable results.” KSR, 550 U.S. at 416. That is the 

case here. Consequently, the Board did not err in concluding that combining Bambot with Weigl rendered the 

claims obvious, regardless of Weigl’s extra-vessel sensors. 
8 UNIV. OF MD. BIOTECH v. PRESENS PRECISION SENSING GMBH

Maryland also argues that Weigl teaches away from 

the claimed invention because: (1) Weigl’s carbon dioxide 

sensor is unstable; (2) each of Weigl’s flow-through units 

has only one sensor, not multiple sensors; (3) Weigl’s 

various outlets are inconsistent with the claimed invention’s “continuous volume” limitation; and (4) Weigl’s 

device is “invasive” because it requires extra-vessel sensors. 

Presens responds that Maryland’s teaching away arguments are not supported by the references’ teachings or 

improperly attempt to distinguish Weigl from technical 

features not in the claims. 

We agree with Presens that Maryland’s teaching 

away arguments do not demonstrate Board error. Like its 

argument based on the positioning of Weigl’s sensors, 

Maryland’s teaching away arguments narrowly focus on 

Weigl’s physical arrangement. But “mere disclosure of 

alternative designs does not teach away.” In re Fulton, 

391 F.3d 1195, 1201 (Fed. Cir. 2004). Rather, teaching 

away requires “clear discouragement” from implementing 

a technical feature. In re Ethicon, Inc., 844 F.3d 1344, 

1351 (Fed. Cir. 2017). 

Maryland directs us to no such discouragement. Substantial evidence supports the Board’s finding that a 

person of ordinary skill would not be limited to Weigl’s 

unstable carbon dioxide sensor, but would instead look to 

Bambot’s alternative carbon dioxide sensor. The same is 

true regarding Weigl’s flow-through units, outlets, and 

alleged invasiveness, as the Board’s finding that Bambot 

taught cultivation vessels with sensors embedded inside, 

which did not require flow-through units or outlets, is 

supported by substantial evidence. See supra at 7. While 

Weigl did adopt an “alternative design[]” to Bambot,

Fulton, 391 F.3d at 1201, it did not provide “clear discouragement” from monitoring carbon dioxide with a stable
UNIV. OF MD. BIOTECH v. PRESENS PRECISION SENSING GMBH 9

sensor or from using intra-vessel sensors, Ethicon, 844 

F.3d at 1344. 

We have considered Maryland’s remaining arguments 

and find them unpersuasive.

CONCLUSION

Because the Board did not err in concluding that the 

combination of Bambot and Weigl renders the claims of 

the ’532 patent obvious, we affirm. As such, we do not 

reach Presens’s conditional cross-appeal. 

AFFIRMED