United States Court of Appeals for the Federal Circuit 

2006-1507 

(Serial No. 08/405,454) 

IN RE JOHN B. SULLIVAN and FINDLAY E. RUSSELL 

Lawrence M. Green, Wolf, Greenfield & Sacks, P.C., of Boston, Massachusetts, 

argued for appellants. With him on the brief were Michael T. Siekman and Charles T.

Steenburg. 

 

Janet A. Gongola, Associate Solicitor, United States Patent and Trademark 

Office, of Arlington, Virginia, argued for the Director of the United States Patent and 

Trademark Office. With her on the brief was Stephen Walsh, Acting Solicitor. 

Appealed from: United States Patent and Trademark Office 

 Board of Patent Appeals and Interferences 

 
United States Court of Appeals for the Federal Circuit 

2006-1507 

(Serial No. 08/405,454) 

IN RE JOHN B. SULLIVAN and FINDLAY E. RUSSELL 

____________________ 

DECIDED: August 29, 2007 

____________________ 

Before NEWMAN, LOURIE, and GAJARSA, Circuit Judges. 

LOURIE, Circuit Judge. 

Sullivan and Russell (collectively “applicant”) appeal from the decision of the 

United States Patent and Trademark Office (“the PTO”) Board of Patent Appeals and 

Interferences (“the Board”) affirming the examiner’s final rejection of claims 40-42 and 

50 of application Serial No. 08/405,454 (“the ’454 application”) under 35 U.S.C. § 103 

as having been obvious over two prior art references. In re Sullivan, No. 2006-0220 

(B.P.A.I. Mar. 30, 2006). Because the Board failed to give any weight to the rebuttal 

evidence of record, we vacate the Board’s decision and remand for further proceedings. 

BACKGROUND 

 The subject matter of the appeal relates to an antivenom composition used to 

treat venomous bites from a snake of the Crotalus genus, i.e., a rattlesnake. An 
antivenom is created by injecting a small amount of the targeted venom into an animal 

such as a horse, sheep, goat, or rabbit. The animal will suffer an immune response to 

the venom, producing antibodies against the venom’s active molecule. Those 

antibodies can then be harvested from the animal’s blood and used to treat humans 

who have been injected with venom from a snake bite. 

A whole antibody molecule, commonly referred to as an immunoglobulin, can be 

thought of as a Y-shaped protein comprised of three fragments. The v-shaped portion 

of the Y-shaped protein is called a F(ab)2 fragment. When separated, each arm of the 

v-shaped portion is called, in turn, a Fab fragment. F(ab)2 and Fab fragments recognize 

and bind to specific antigens, such as the toxin in rattlesnake venom. The lower stem of 

the Y-shaped antibody is called the Fc fragment and is not involved in antigen binding. 

Diagrams of an antibody and its components are provided below for reference. The 

diagram on the left shows a whole antibody and indicates the Fc region and the Fab 

region. The Fab region can be considered a F(ab)2 fragment. The diagram on the right 

shows two Fab fragments that are separated from the Fc region. 

 

An intact antibody, F(ab)2, and Fab fragments have separate properties and 

utilities. Since 1969, most commercially available antivenom products have consisted 

of a class of whole antibodies, known as immunoglobulin G (“IgG”), but there have also 

2006-1507 2
been antivenom products that comprised only F(ab)2 fragments. Although antivenom 

products consisting of either IgG or F(ab)2 fragments are effective at binding to venom 

toxins, they often invoke adverse immune reactions in humans. Researchers did not 

experiment with antivenoms containing only Fab fragments because it was believed that 

their unique properties would prevent them from decreasing the toxicity of snake 

venom. Sullivan discovered, however, that Fab fragments are effective at neutralizing 

the lethality of rattlesnake venom, while reducing the occurrence of adverse immune 

reactions in humans. 

Applicant filed the ’454 application with claims directed to an antivenom 

composition comprising Fab fragments that bind specifically to venom from snakes of 

the Crotalus genus and a pharmaceutical carrier.1 Representative claim 40, as 

originally filed, reads as follows: 

An antivenom composition comprising Fab fragments which bind 

specifically to a venom of a snake of the Crotalus genus and which are 

essentially free from contaminating Fc as determined by 

immunoelectrophoresis using anti-Fc antibodies, and a pharmaceutically 

acceptable carrier. 

The examiner rejected the claim under 35 U.S.C. § 103 as being obvious over 

Sullivan2 in view of Coulter3 and two additional references. In the first appeal to the 

 1

 In the patent application as initially filed, there were also claims directed to 

a process for isolating the Fab fragments. The examiner required a restriction of the 

claims, and the inventors initially pursued the set of process claims. Those claims 

ultimately matured into U.S. Patent 4,849,352. 

2

 J.B. Sullivan, Jr. & F.E. Russell, Isolation and Purification of Antibodies to 

Rattlesnake Venom by Affinity Chromatography, 25 Proc. W. Pharmacology Soc. 185, 

185-92 (1982). 

3

 Alan Coulter & Rodney Harris, Simplified Preparation of Rabbit Fab 

Fragments, 59 J. Immunological Methods 199, 199-203 (1983). 

2006-1507 3
Board, the Board affirmed the rejection of claim 40 as being obvious, but only relied 

upon Sullivan and Coulter for its rejection. In re Sullivan, No. 2001-1255 (B.P.A.I. Jan. 

29, 2003). The Board found that Sullivan teaches whole antibodies purified from horse 

serum for use against venom from rattlesnakes, but fails to teach the use of Fab 

fragments. The Board also found that Coulter discloses a method for producing Fab 

fragments in place of whole antibodies. The Board noted that Coulter further teaches 

using Fab fragments in enzyme immunoassays (“EIAs”)4 to detect textilotoxin, a kind of 

snake toxin from the venom of the Australian brown snake. Also, Coulter teaches that 

Fab fragments used in EIAs yielded results similar to those obtained with whole IgG. 

Based upon those teachings, the Board agreed with the examiner that all the 

limitations of claim 40 were disclosed in Sullivan and Coulter. The Board concluded 

that a person of ordinary skill in the art would have been motivated to produce Fab 

fragments for use in EIAs to detect the venom from rattlesnakes because Coulter 

teaches that Fab fragments are able to detect textilotoxins. The Board further stated 

that the term “antivenom” in the preamble could not render claim 40 patentable over 

Sullivan and Coulter, reasoning that “the mere statement of new use, in this case ‘an 

antivenom’ for an otherwise old or obvious composition, cannot render a claim to the 

composition patentable.” Sullivan, No. 2001-1255, slip op. at 9. The Board also held 

that, although it was not previously addressed, Coulter discloses collecting Fab 

fragments in a phosphate buffered saline (“PBS”), which is a pharmaceutically 

 4

 An EIA is a biochemical test that measures the level of a substance in a 

biological sample, such as serum or urine, using the reaction of an antibody to its 

antigen. Based on the amount of antibody detected, the amount of substance bound to 

the antibody can be determined. 

2006-1507 4
acceptable carrier. The Board concluded that the asserted claims were prima facie 

obvious over the combination of Sullivan in view of Coulter. 

The Board stated that since its decision contained a new ground of rejection, the 

applicant could either move for reconsideration by the Board or return to prosecution 

before the examiner.5 Applicant chose to return to prosecution before the examiner. 

Applicant then amended claim 40 to its current form, adding language to the preamble 

and to the end of the claim. Amended claim 40 reads as follows, with the underlined 

portions identifying the portions of the claim that were added: 

An antivenom pharmaceutical composition for treating a snakebite victim, 

comprising Fab fragments which bind specifically to a venom of a snake of 

the Crotalus genus and which are essentially free from contaminating Fc 

as determined by immunoelectrophoresis using anti-Fc antibodies, and a 

pharmaceutically acceptable carrier, wherein said antivenom 

pharmaceutical composition neutralizes the lethality of the venom of a 

snake of the Crotalus genus. 

 The examiner rejected amended claims 40-42 and 506

 under 35 U.S.C. § 103 as 

obvious over the combination of Sullivan and Coulter. The examiner found that the 

additional language in claim 40 did not render the claim patentable. The examiner 

reasoned that the originally claimed composition contained the same components as 

the amended claimed composition. The examiner issued a final rejection, and applicant 

appealed to the Board. In the second appeal to the Board, the Board noted that there 

 5

 Under 37 C.F.R. § 41.50(b)(1), when the Board issues a new ground of 

rejection, an applicant may “[s]ubmit an appropriate amendment of the claims so 

rejected . . . and have the matter reconsidered by the examiner, in which event the 

proceeding will be remanded to the examiner. . . . Should the examiner reject the 

claims, appellant may again appeal to the Board pursuant to this subpart.” 

6

 According to Sullivan, the claims stand or fall together. Thus, the Board 

limited its discussion to representative independent claim 40. Similarly, we only discuss 

claim 40. 

2006-1507 5
were only two differences between original claim 40 and amended claim 40: (1) the 

recitation of intended use that states that the pharmaceutical composition is for treating 

a snakebite victim, and (2) the functional limitation that requires the pharmaceutical 

composition to neutralize the lethality of the venom of a rattlesnake. The Board 

addressed each amendment in turn. 

With regard to the first amended portion, the Board again stated that a statement 

of a new use for an otherwise old or obvious composition cannot render a claim to the 

composition patentable. The Board noted that the phrase, “an antivenom 

pharmaceutical composition for treating a snakebite victim,” simply states the intended 

use for the invention. Sullivan, No. 2006-0220, slip op. at 11. The Board also noted 

that “all the elements of appellants’ claimed composition are accounted for in the prior 

art relied upon on this record.” Id. at 13. Thus, the Board held that the amended 

preamble did not render the claim patentable. 

Most relevant to the resolution of the appeal, the Board then stated in a footnote: 

“The remainder of appellants [sic] arguments on this record, in addition to the 

Declarations of record, relate to the use of the claimed composition as an antivenom. 

Since we have placed not [sic] weight on the intended use of appellants’ composition 

we do not address these arguments or the Declarations.” Id. at 13 n.7. 

The Board then considered the second amended portion of the claim, which 

includes the limitation of neutralizing the lethality of the rattlesnake venom. The Board 

found that Coulter teaches that neutralization tests performed in mice showed that 

whole antibodies and Fab fragments were equivalent in their neutralizing ability. 

Accordingly, the Board found that the additional requirement that the composition of 

2006-1507 6
claim 40 neutralize the lethality of the venom of a rattlesnake did not render the claim 

patentable. The Board thus held that the composition taught by the combination of 

Sullivan and Coulter would have been expected by a person of ordinary skill in the art at 

the time the invention was made to neutralize the lethality of the venom of a rattlesnake. 

Applicant timely appealed, and we have jurisdiction pursuant to 28 U.S.C. 

§ 1295(a)(4)(A). 

DISCUSSION 

 The determination whether an invention would have been obvious under 35 

U.S.C. § 103 is a legal conclusion based on underlying findings of fact. In re Kotzab, 

217 F.3d 1365, 1369 (Fed. Cir. 2000). We review the Board’s legal conclusion of 

obviousness de novo and its underlying factual determinations for substantial evidence. 

In re Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000). “Substantial evidence requires 

the reviewing court to ask whether a reasonable person might find that the evidentiary 

record supports the agency’s conclusion.” On-Line Careline, Inc. v. Am. Online, Inc., 

229 F.3d 1080, 1085 (Fed. Cir. 2000). 

 On appeal, applicant argues that the Board failed to establish that the claimed 

composition was prima facie obvious over Sullivan in view of Coulter. Applicant 

specifically argues that a person having ordinary skill in the art would not have been 

motivated to combine Sullivan and Coulter to achieve the result of “neutralizing the 

lethality of the rattlesnake venom.” Applicant argues that Coulter teaches using Fab 

fragments to detect, rather than treat, venom. Applicant further argues that, even if the 

Board had shown that the invention was prima facie obvious, the Board erred by 

ignoring extensive rebuttal evidence. According to applicant, the Board failed to 

2006-1507 7
consider three expert declarations on the ground that they only describe the intended 

use of the composition. Applicant contends that the declarations describe how the prior 

art taught away from using Fab fragments to neutralize rattlesnake venom, how a 

person having ordinary skill in the art would not have known how to use Fab fragments 

to neutralize rattlesnake venom, and how Fab fragment antivenom exhibits an 

unexpected property. Moreover, applicant contends that the rebuttal evidence relates to 

objective indicia of nonobviousness, and that the Board erred as a matter of law by 

failing to consider that evidence. 

The Director of the PTO responds that the Board correctly determined that the 

claimed composition was prima facie obvious over Sullivan in view of Coulter. The 

Director asserts that all the limitations of claim 40 are taught by Sullivan and Coulter 

and that the motivation to combine those references is found in the references 

themselves and the knowledge of those skilled in the art. According to the Director, the 

amendments to claim 40 merely relate to the use of the claimed product and do not 

render the claim patentable because a new use of an obvious composition is not 

patentable. The Director also submits that the Board did consider the declarations and 

correctly gave them no weight because they only relate to the use of the claimed 

composition. The Director also contends that applicant’s argument as to secondary 

considerations such as unexpected results and commercial success is being raised for 

the first time on appeal and should be deemed waived. 

We agree with applicant that the Board improperly failed to consider the rebuttal 

evidence and we therefore vacate the Board’s decision and remand for the Board to 

consider the declarations. It is well settled that the PTO “bears the initial burden of 

2006-1507 8
presenting a prima facie case of unpatentability. . . . However, when a prima facie case 

is made, the burden shifts to the applicant to come forward with evidence and/or 

argument supporting patentability.” In re Glaug, 283 F.3d 1335, 1338 (Fed. Cir. 2002). 

Rebuttal evidence is “merely a showing of facts supporting the opposite conclusion.” In 

re Piasecki, 745 F.2d 1468, 1472 (Fed. Cir. 1984). Evidence rebutting a prima face 

case of obviousness can include: “evidence of unexpected results,” Pfizer, Inc. v. 

Apotex, Inc., 480 F.3d 1348, 1369 (Fed. Cir. 2007), evidence “that the prior art teaches 

away from the claimed invention in any material respect,” In re Peterson, 315 F.3d 

1325, 1331 (Fed. Cir. 2003), and evidence of secondary considerations, such as 

commercial success and long-felt but unresolved needs, WMS Gaming, Inc. v. Int’l 

Game Tech., 184 F.3d 1339, 1359 (Fed. Cir. 1999). When a patent applicant puts forth 

rebuttal evidence, the Board must consider that evidence. See In re Soni, 54 F.3d 746, 

750 (Fed. Cir. 1995) (stating that “all evidence of nonobviousness must be considered 

when assessing patentability”); In re Sernaker, 702 F.2d 989, 996 (Fed. Cir. 1983) (“If, 

however, a patent applicant presents evidence relating to these secondary 

considerations, the board must always consider such evidence in connection with the 

determination of obviousness.”). 

For purposes of this appeal, we assume that the Board established a prima facie 

case of unpatentability under § 103. There was no showing of unpatentability under 

§ 102, as the subject matter of claim 40 was not described in either Sullivan or Coulter. 

We accept, however, that a prima facie case of obviousness was established because 

Sullivan teaches whole antibodies for use against rattlesnake venom and Coulter 

teaches using Fab fragments to detect venom of a different snake. It was not 

2006-1507 9
unreasonable for one skilled in the art of snake venom to consider that a Fab fragment 

of a whole antibody that neutralizes one type of venom might be used to neutralize the 

venom of another species. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. __, 2007 WL 

1237837, at *13 (2007) (stating that “if a technique has been used to improve one 

device, and a person of ordinary skill in the art would recognize that it would improve 

similar devices in the same way, using the technique is obvious unless its actual 

application is beyond his or her skill”). 

Accepting that there was a prima facie obviousness case, however, there was 

rebuttal evidence. While the Director argues that that evidence only relates to use of an 

obvious composition, that is incorrect. Whether the composition would have been 

obvious cannot be determined without considering evidence attempting to rebut the 

prima facie case. 

We therefore turn our attention to the Board’s consideration, or lack thereof, of 

the rebuttal evidence submitted by applicant. Upon our review of the record, we find 

that there were three pieces of evidence in the record that the applicant submitted to the 

PTO to rebut a prima facie finding of obviousness. First, in response to the examiner’s 

first Office Action that rejected the originally filed claims, applicant relied upon and 

submitted a declaration by Dr. Damon Smith, an expert involved in developing 

antivenoms for different snake species. That declaration discusses the state of the prior 

art for antivenoms and discusses why, since 1969, the only commercially available 

antivenom products included either intact IgG or F(ab)2 fragments. The declaration 

further discusses why those skilled in the art would not have expected Fab fragments to 

2006-1507 10
effectively neutralize venom. That declaration therefore is relevant as evidence that the 

prior art taught away from the claimed invention. 

The second piece of rebuttal evidence submitted to the PTO is a declaration by 

one of the inventors, Dr. John B. Sullivan. After the claims were finally rejected, 

applicant filed a continuation application in March 1995 and filed the second declaration 

by Dr. Sullivan. That declaration also discusses why those having ordinary skill in the 

art would not have expected Fab fragments to be useful as antivenoms. The 

declaration extensively explains the unique properties of whole antibodies and F(ab)2

fragments, including that the body does not clear them as quickly as it clears Fab 

fragments. Because venom remains in the body for an extended period of time and the 

body quickly clears Fab fragments, the declaration discusses why experts did not 

experiment with Fab fragments as an antivenom. Also, the declaration states that the 

success of equine-derived antivenom containing IgG results from its possessing an 

extra disulfide bond that allows IgG to bind to repeating protein antigens. A Fab 

fragment does not have such a bond, and the experts believed that Fab fragment 

antivenom would therefore not negate the toxic effects of venom. The declaration 

further explains that the inventors conducted experiments and clinical trials using Fab 

fragment antivenom and discovered, contrary to what the experts had believed, that it 

effectively neutralizes the toxicity of rattlesnake venom, while also decreasing the 

occurrence of adverse immune reactions in humans. This inventor’s declaration thus 

describes an unexpected property or result from the use of Fab fragment antivenom. 

The third piece of rebuttal evidence submitted by the applicant is a declaration by 

Dr. Russell, one of the inventors. The first version of this declaration appears to have 

2006-1507 11
been submitted after the first Office Action of the continuation application. The 

examiner considered it but found it unpersuasive to overcome a prima facie case of 

unpatentability. That declaration further discusses why those having ordinary skill in the 

art expected antivenoms comprising Fab fragments to fail. 

The Board failed to consider each of these declarations. The Board stated in a 

footnote that the declarations of record relate only to the use of the claimed composition 

as an antivenom, and thus the Board expressly declined to give any meaningful 

consideration to them. Sullivan, No. 2006-0220, slip op. at 13 n.7. As stated above, 

when an applicant puts forth relevant rebuttal evidence, as it did here, the Board must 

consider such evidence. The claimed composition cannot be held to have been obvious 

if competent evidence rebuts the prima facie case of obviousness. By failing to 

consider the submitted evidence, the Board thus committed error. That is not to 

suggest that the Board’s finding of obviousness must be overturned in light of the 

evidence; rather, the Board must give the declarations meaningful consideration before 

arriving at its conclusion. 

Moreover, the Board was mistaken to assert that the declarations only relate to 

the use of the claimed composition. The declarations do more than that; they purport to 

show an unexpected result from use of the claimed composition, how the prior art 

taught away from the composition, and how a long-felt need existed for a new 

antivenom composition. While a statement of intended use may not render a known 

composition patentable, the claimed composition was not known, and whether it would 

have been obvious depends upon consideration of the rebuttal evidence. Had the Board 

2006-1507 12
considered or reviewed the declarations in any meaningful way, it might have arrived at 

a different conclusion than it did. 

Furthermore, the Board’s focus on the intended use of the claimed composition 

misses the mark. The Board cites In re Zierden, 411 F.2d 1325 (CCPA 1969), for the 

proposition that a statement of a new use for an otherwise old or obvious composition 

cannot render a claim to the composition patentable. In that case, applicant conceded 

that his composition was distinguished from the composition disclosed in a prior art 

patent only by the statement of intended use. Our predecessor court held that that 

intended use for the known composition could not render the claim patentable. In this 

case, applicant does not concede that the only distinguishing factor of its composition is 

the statement of intended use and, in fact, extensively argues that its claimed 

composition exhibits the unexpected property of neutralizing the lethality of rattlesnake 

venom while reducing the occurrence of adverse immune reactions in humans. Such a 

use and unexpected property cannot be ignored. See In re Papesch, 315 F.2d 381, 391 

(CCPA 1963) (“From the standpoint of patent law, a compound and all of its properties 

are inseparable; they are one and the same thing. . . . There is no basis in law for 

ignoring any property in making such a comparison.”). The issue here is not whether a 

claim recites a new use, but whether the subject matter of the claim possesses an 

unexpected use. That unexpected property is relevant, and thus the declarations 

describing it should have been considered by the Board. 

Finally, we reject the Director’s argument that the applicant for the first time on 

appeal argues secondary considerations, such as unexpected results, and therefore 

that the argument should be considered waived. As discussed above, the applicant 

2006-1507 13
2006-1507 14

submitted the declarations to the examiner during prosecution, and the declarations 

extensively describe the unexpected property of Fab fragments neutralizing the lethality 

of rattlesnake venom and how this was not known in the prior art. Thus, we do not 

consider that argument to have been waived. 

CONCLUSION 

 For the foregoing reasons, we vacate the Board’s decision and remand for the 

Board to consider the declarations of record. 

VACATED and REMANDED