Antonio J. Grillo-López

Patent Trials and Appeals Board

Aug 28, 2019

13524837 - (D) (P.T.A.B. Aug. 28, 2019)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/524,837 06/15/2012 Antonio J. Grillo-López P04644-US-5 8212
9157 7590 08/28/2019
GENENTECH, INC.
1 DNA WAY
SOUTH SAN FRANCISCO, CA 94080
EXAMINER
KOLKER, DANIEL E
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
08/28/2019 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
docketing-uspto-d@gene.com
pair_roche@firsttofile.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________________

Ex parte ANTONIO J. GRILLO-LOPEZ1
____________________

Appeal 2018-006082
Application 13/524,837
Technology Center 1600
____________________

Before JEFFREY N. FREDMAN, TAWEN CHANG, and DAVID COTTA,
Administrative Patent Judges.

CHANG, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of treating patients with relapsed low grade or follicular lymphoma,
which have been rejected as anticipated and obvious. We have jurisdiction
under 35 U.S.C. § 6(b).
We AFFIRM, but designate our affirmance as a new ground of
rejection.

1 Appellant identifies the Real Party in Interest as Biogen Inc. (Appeal Br.
3.)
Appeal 2018-006082
Application 13/524,837

2
STATEMENT OF THE CASE
“The invention relates to the use of anti-CD20 antibodies or fragments
thereof in the treatment of B-cell lymphomas, particularly the use of such
antibodies and fragments in combined therapeutic regimens.” (Spec. 1:14–
16.)
Claims 15–17 are on appeal and reproduced below:
15. A method of treating patients with relapsed low grade or
follicular lymphoma comprising administering rituximab at a
dose of 375mg/m2 intravenously once weekly for a total of four
infusions administered on days 1, 8, 15, and 22, wherein the
initial infusion rate is 50 mg/h on day 1, and the initial infusion
rate on days 8, 15, and 22 is faster than 50 mg/h if no toxicity
was seen during the infusion on day 1.

16. A method of treating patients with relapsed low grade or
follicular lymphoma comprising administering rituximab at a
dose of 375mg/m2 intravenously once weekly for a total of four
infusions administered on days 1, 8, 15, and 22, wherein the
initial infusion rate is 50 mg/h on day 1, and the initial infusion
rate on days 8, 15, and 22 is faster than 50 mg/h if no toxicity
was seen during the infusion on day 1, and wherein infusions
are interrupted if an adverse event occurs and resumed once the
adverse event subsides.

17. A method of treating patients with relapsed low grade or
follicular lymphoma comprising administering chimeric anti-
CD20 monoclonal antibody at a dose of 375mg/m2
intravenously once weekly for a total of four infusions
administered on days 1, 8, 15, and 22, wherein the initial
infusion rate is 50 mg/h on day 1, and the initial infusion rate
on days 8, 15, and 22 is faster than 50 mg/h if no toxicity was
seen during the infusion on day 1, and wherein infusions are
interrupted if an adverse event occurs and resumed once the
adverse event subsides, and wherein the chimeric anti-CD20
comprises a light chain variable region comprising the amino
acid sequence in SEQ ID NO: 1 and a heavy chain variable
Appeal 2018-006082
Application 13/524,837

3
region comprising the amino acid sequence in SEQ ID NO: 2,
and human gamma 1 heavy-chain and kappa light-chain
constant region sequences.
(Appeal Br. 26–27 (Claims App.).)
The Examiner rejects claims 15–17 under pre-AIA 35 U.S.C. § 102(b)
as being anticipated by the prescribing information for RITUXAN®, dated
November 1997. (Ans. 5.)
The Examiner rejects claims 15–17 under pre-AIA 35 U.S.C. § 103(a)
as being unpatentable over the public hearing transcript of the nineteenth
meeting of the Biological Response Modifiers Advisory Committee, which
is a part of the Food and Drug Administration’s Center for Biological
Evaluation and Research, held on July 25, 1997 (hereinafter “FDA
Transcript”). (Id.)
I.
Issue
The Examiner has rejected claims 15–17 as anticipated by the
November 1997 prescribing information for RITUXAN®, a brand name
under which rituximab is sold. The Examiner finds that the claimed
invention are only entitled to priority to the filing date of the instant
application, June 15, 2012, because “the scope of the inventions of claims
15–17 are not disclosed in the parents applications to which priority is
claimed.” (Ans. 3.) The Examiner finds that the November 1997
prescribing information for RITUXAN® discloses the methods of claims
15–17. (Id.)
Appellant does not dispute that the November 1997 prescribing
information for RITUXAN® discloses the methods of claims 15–17.
Appeal 2018-006082
Application 13/524,837

4
However, Appellant contends that the claims are entitled to the priority date
of August 11, 1998 and that the November 1997 prescribing information is
thus not prior art under 35 U.S.C. § 102(b). Appellant further contends that
the Grillo-Lopez Declaration2 effectively establishes that the invention
antedates November 1997 under 37 C.F.R. § 1.131, and that the prescribing
information is therefore also not prior art under 35 U.S.C. § 102(a).
The issues with respect to this rejection are (1) whether the instant
application is entitled to the priority date of August 11, 1998 and, if so, (2)
whether the Grillo-Lopez Declaration establishes that the invention
antedates the November 1997 prescribing information for RITUXAN®.
Analysis
Pre-AIA 35 U.S.C. § 102(b)
On balance, we find that Appellant has the better arguments.
Provisional Application 60/096,180, the application to which priority is
claimed, includes a partial copy of the McLaughlin reference.3 The
Examiner asserts that McLaughlin is “limited to specific infusion rates for
days 8,[ ]15,[ ]22 for the dose of 375[mg]/[m2] of administered antibody,”

2 Declaration of Antonio J. Grillo-Lopez, M.D. under 37 C.F.R. § 1.131
(Mar. 4, 2013) (“Grillo-Lopez Declaration”).
3 Peter McLaughlin, Rituximab Chimeric Anti-CD20 Monoclonal Antibody
Therapy for Relapsed Indolent Lymphoma: Half of Patients Respond to a
Four-Dose Treatment Program, 16 J. CLINICAL ONCOLOGY 2825 (1998)
(“McLaughlin”). We note that the copy of McLauglin submitted as part of
the provisional application omits the Acknowledgement and References
sections and also numbers its pages starting from page one (rather than page
2825). Because the Examiner in his analysis appears to cite to the page
numbers of the McLaughlin reference itself rather than to the copy included
as part of the provisional application, we do so as well to maintain
consistency.
Appeal 2018-006082
Application 13/524,837

5
(i.e., “an infusion rate resulting in mean administration of times of 3.5, 3.3
and 3.3 hours respectively”), whereas the claims “encompasses any rate
faster than 50 mg/h” on days 8, 15, and 22 if no toxicity was seen during the
infusion on day 1. (Ans. 3–4.)
We are not persuaded. As Appellant points out, McLaughlin teaches
intravenously administering, to patients with relapsed low grade or follicular
lymphoma, 375 mg/m2 of rituximab once a week for a total of four infusions
(days 1, 8, 15, and 22), as recited for instance in claim 15. (McLaughlin
2825, right column; 2826, left column.) McLaughlin further teaches that
“[t]he initial rate was 50 mg/h, with subsequent infusion rate increase if no
toxicity was seen.” (Id. at 2826, left column.) Moreover, although
McLaughlin discloses that in its study actual mean durations of the infusions
were 3.5, 3.3, and 3.3 hours, respectively for days 8, 15, and 22
(McLaughlin 2828–2829), the First Levy Declaration4 explains that a skilled
artisan would understand a safe infusion rate to be patient-dependent and
thus would not read McLaughlin narrowly as only disclosing these specific
infusion rates for days 8, 15, and 22. (First Levy Decl. ¶ 17.)
In light of McLaughlin’s general disclosure to increase subsequent
infusion rates from the initial rate of 50 mg/h if no toxicity were seen, as
well as the discussion in the First Levy Declaration, we disagree with the
Examiner that a skilled artisan would understand McLaughlin’s disclosure to
be limited to the subsequent infusion rates actually used in the study (i.e.,
infusion rates resulting in mean infusion durations of 3.5, 3.3, and 3.3 hours
on days 8, 15, and 22).

4 Declaration of Ronald Levy under 37 C.F.R. § 1.132 (Nov. 22, 2016)
(“First Levy Declaration”).
Appeal 2018-006082
Application 13/524,837

6
In response to the First Levy Declaration, the Examiner emphasized
that
there is no disclosure in McLaughlin et al. that the 375[mg]/
[m2] of administered antibody can be delivered at any and all
rates faster than 50 mg/h. For example, the limitation
encompass delivery of all of the antibody in 15 minutes or one
hour wherein such infusion rates are not disclosed in
McLaughlin et al.
(Id. at 4.) In short, the Examiner asserts that the provisional application fails
to provide a written description of the full scope of the infusion rate claimed
(i.e., faster than 50 mg/h).
We are not persuaded because, as discussed above, McLaughlin in
fact generally discloses increasing subsequent infusion rates from the initial
rate of 50 mg/h if no toxicity were seen, without placing an upper limit on
the subsequent infusion rate. (McLaughlin 2826, left column.) To the
extent the Examiner is asserting that McLaughlin does not enable a skilled
artisan to make or use the full scope of the invention, the Examiner has not
provided persuasive evidence contradicting statements in the First Levy
Declaration that a skilled artisan would be able to determine the appropriate
infusion rate for a given patient in light of McLaughlin’s disclosure. Cf.
Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005) (“It is not necessary
that every permutation within a generally operable invention be effective in
order for an inventor to obtain a generic claim.”).
Accordingly, we find that, on the record before us, the claims on
appeal are entitled to the priority date of August 11, 1998, the filing date of
the ’180 provisional application.
Appeal 2018-006082
Application 13/524,837

7
Pre-AIA 35 U.S.C. § 102(a)
Because the prescribing information for RITUXAN® cited as prior art
by the Examiner is dated November 1997, less than one year before the
priority date of August 11, 1998, the prescribing information for
RITUXAN® is not prior art under pre-AIA 35 U.S.C. § 102(b). This does
not end our inquiry because, under pre-AIA 35 U.S.C. § 102(a),
RITUXAN® prescribing information may still be prior art if it predates
Appellant’s invention of the claimed subject matter.
Under 37 C.F.R. § 1.131, a party may file “an oath or declaration to
establish invention of the subject matter of the rejected claim prior to the
effective date of the reference.” 37 C.F.R. § 1.131(a) (2015). In order to
establish such prior invention,
[t]he showing of facts for an oath or declaration . . . shall be
such, in character and weight, as to establish reduction to
practice prior to the effective date of the reference, or
conception of the invention prior to the effective date of the
reference coupled with due diligence from prior to said data to a
subsequent reduction to practice.
37 C.F.R. § 1.131(b) (2015). We therefore turn next to a consideration of
whether the Grillo-Lopez Declaration5 shows that the invention of the
claimed subject matter antedates the November 1997 prescribing
information for RITUXAN®.
We again find that Appellant has the better arguments. Exhibit A of
the Grillo-Lopez Declaration is a report dated January 1997, which describes
a study conducted at 31 sites the United States and Canada between April
25, 1995 and April 19, 1996. (Grillo-Lopez Decl. ¶¶ 1–2, Ex. A cover page,

5 Declaration of Antonio J. Grillo-Lopez, M.D. under 37 C.F.R. § 1.131
(Apr. 17, 2017) (“Grillo-Lopez Declaration”).
Appeal 2018-006082
Application 13/524,837

8
xxv.) The study describes intravenously administering to patients with
relapsed low-grade or follicular lymphoma 375 mg/m2 of IDEC-C2B8
(rituximab) once weekly for four infusions. (Id. ¶¶ 2–3, Exhibit A cover
page, xxv, 15–16; see also id. at Exhibit A 38 (mean administered dose per
infusion of 373.5 mg/m2 (range 23.4–390.6 mg/m2) including incomplete
infusions).) The study states that
[t]he dose rate for the first IDEC-C2B8 infusion was to
be 50 mg/hour for the first hour. If no toxicity was seen,
the dose rate was allowed to be escalated in 50 mg
increments at 30-minute intervals to a maximum of 300
mg/hour. If the first IDEC-C2B8 dose was well
tolerated, the starting flow rate for subsequent infusions
was to be 100 mg/hour increasing to a maximum of 400
mg/hour.
(Id. at Ex. A 16; see also id. ¶¶ 3–4.) The study also states that “some patients
required slowing of infusion rate or temporary infusion interruption due to
infusion-related adverse events.” (Id. at Ex. A 38; see also id. at Ex. A 16.)
The Examiner has not disputed that the study described in Exhibit A
of the Grillo-Lopez Declaration constitutes conception and reduction to
practice of the invention of claims 15–17 prior to the effective date of the
cited reference (i.e., the November 1997 prescribing information for
RITUXAN®). However, the Examiner argues that “the Grillo-Lopez
declaration is defective in that it states in paragraph 1 that invention was
conceived and reduced to practice in the US whilst page xxv of materials
filed in said declaration states that study took place in the US and Canada.”
(Ans. 9–10.)
We are not persuaded. Although Dr. Grillo-Lopez does not
specifically state that part of the study took place in Canada, we do not find
the statement in his declaration to be inaccurate because part of the study
Appeal 2018-006082
Application 13/524,837

9
also took place in the United States. (Grillo-Lopez Decl. Ex. A xxv (study
took place in 31 sites in the United States and Canada).) Furthermore,
Canada is a NAFTA country. 37 C.F.R. § 1.131(a) permits prior invention
to be established in a non-U.S. NAFTA country after December 8, 1993, and
the study at issue took place after that date. (Id. (study took place between
April 25, 1995 and April 19, 1996).)
Accordingly, we reverse the Examiner’s rejection of claims 15–17 as
anticipated by the November 1997 prescribing information for RITUXAN®.
II.
Issue
The Examiner has rejected claims 15–17 as obvious over FDA
Transcript. The Examiner finds that the FDA Transcript teaches all of the
limitations of the claims except that it does not specifically teach that “the
initial infusion rate [for rituximab] on day 8, 15, 22 was greater than 50
mg/hour if no toxicity was seen on day 1.” (Ans. 6.) However, the
Examiner finds that a skilled artisan would have been motivated to practice
the claimed method with a reasonable expectation of success, because
“increasing the infusion rate results in a faster treatment for the patient” and
the FDA Transcript teaches that “the antibody is administered at an initial
intravenous rate of 50 mg/hour and increased to a maximal rate of 150
mg/hour wherein the majority of adverse events occur with the first
infusion.” (Id. at 6–7.)
Appellant contends that the FDA Transcript is not a printed
publication within the meaning of 35 U.S.C. § 102(a) or § 102(b), or a
public use within the meaning of 35 U.S.C. § 102(b). (Appeal Br. 24; Reply
Appeal 2018-006082
Application 13/524,837

10
Br. 5–8.6) Appellant also contends that the FDA Transcript does not provide
“motivation or reasonable expectation of success that an initial infusion rate
faster than 50 mg/h for the infusions on days 8, 15, or 22 should be tried,
much less that it would be safe and effective.” (Appeal Br. 20.)
Appellant does not separately argue the claims. We therefore limit
our analysis to claim 15 as representative. The issues with respect to this
rejection are (1) whether the FDA Transcript is a printed publication or a
public use within the meaning of 35 U.S.C. § 102 (b)7 and if so, (2) whether,
based on the FDA Transcript, a skilled artisan would have had reason to
treat patients with rituximab using an initial infusion rate of greater than 50
mg/hour on day 8, 15, and 22 if no toxicity was seen on day 1 of treatment.
Analysis
We agree with the Examiner that the FDA Transcript renders claim 15
obvious.
Whether the FDA Transcript Is Prior Art
As explained by our reviewing court, the key inquiry is whether the
FDA Transcript was made “sufficiently accessible to the public interested in
the art” before the critical date, which is August 11, 1997 in this case for
purposes of 35 U.S.C. § 102(b). Constant v. Advanced Micro-Devices, Inc.,
848 F.2d 1560, 1568 (Fed. Cir. 1988). “A given reference is ‘publicly

6 Appellant’s Reply Brief does not include page numbers. Therefore, we
refer to page numbers in the Reply Brief as if the Reply Brief was numbered
sequentially starting with the first page.
7 Appellant has argued that the FDA Transcript is not a printed publication
under either 35 U.S.C. § 102(a) or § 102(b). Because similar legal analysis
applies in both cases, and because 35 U.S.C. § 102(a) allows Appellant to
“swear behind” the FDA Transcript, we focus our analysis on whether the
FDA Transcript is a printed publication under 35 U.S.C. § 102(b).
Appeal 2018-006082
Application 13/524,837

11
accessible’ upon a satisfactory showing that such document has been
disseminated or otherwise made available to the extent that persons
interested and ordinarily skilled in the subject matter or art exercising
reasonable diligence, can locate it.” Bruckelmyer v. Ground Heaters, Inc.,
445 F.3d 1374, 1378 (Fed. Cir. 2006). “Whether a reference is publicly
accessible is determined on a case-by-case basis based on the ‘facts and
circumstances surrounding the reference’s disclosure to members of the
public.’” Voter Verified, Inc., v. Premier Election Solutions, Inc., 698 F.3d
1374, 1380 (Fed. Cir. 2012) (quoting In re Lister, 583 F.3d 1307, 1311 (Fed.
Cir. 2009)). Bearing the above principles in mind, we find that the FDA
Transcript is a printed publication within the meaning of 35 U.S.C. § 102(b),
as further discussed below.
Appellant contends that “[t]he Examiner offers no evidence that the
[FDA] Transcript was ever actually disseminated before the priority date.”
(Reply Br. 5.) We are not persuaded. We find that the evidence supports
the conclusion that the FDA Transcript was made available to the public
prior to the critical date. In particular, Appellant cites to the Board’s
decision denying institution in IPR2017-010948 to argue that the FDA
Transcript is not a printed publication. (Appeal Br. 24.) That decision refers
to an August 26, 2016 letter from Dynna Bigby (“Bigby Letter”),9 which
explains that, based on procedures in place in 1997, FDA’s Division of

8 Celltrion, Inc. v. Biogen, Inc., IPR2017-01094, Paper No. 12 (Oct. 2,
2017).
9 Celltrion, Inc. v. Biogen, Inc., IPR2017-01094, Ex. 1039. Ms. Bigby is a
Supervisory Administrative Proceedings Officer at the Division of Dockets
Management (“DDM”) at the FDA/Office of the Executive Secretariat.
(Bigby Letter 001.)
Appeal 2018-006082
Application 13/524,837

12
Dockets Management (“DDM”) would have received the FDA Transcript on
Aug. 8, 1997, the date stamped on the transcript. (Bigby Letter 001.) The
Bigby Letter further states that, “[in] 1997, once the DDM received a
document, it [would have] made that document publicly available via the
DDM Public Reading Room.” (Id.) The Bigby Letter concludes that,
therefore, “[f]ollowing August 8, 1997, any member of the public could
have requested and received a copy of the transcript in question by filling
out a reading room request form.”10 (Id.) Appellant has not persuasively
disputed any of the facts recited in the Bigby Letter. Accordingly, we find a
prima facie case exists that the FDA Transcript was disseminated or
otherwise made available before the critical date of August 11, 1997.
We next turn to the question of whether the FDA Transcript was made
available to a sufficient extent to render it a printed publication within the
meaning of § 102(b). Appellant relies on the reasoning articulated in the
Board’s decision denying institution of IPR2017-01094, which found that
the petitioner in that case failed to provide “‘some supported explanation
that . . . availability of the FDA Transcript was in a manner and to an extent
that ‘persons interested and ordinarily skilled in the subject matter or art
exercising ‘reasonable diligence’ would have been able to locate it,’” and
contends that the FDA Transcript was not “publicly accessible” to the extent
required to establish it as a “printed publication” within the meaning of

10 To the extent Appellant’s argument is that there is no evidence a member
of the public actually accessed the document, we are not persuaded. There is
no requirement that a reference be actually accessed by a member of the
public to be a printed publication, so long as it was “disseminated or
otherwise made available” to the extent that an interested and ordinarily
skilled person can locate it by exercising reasonable diligence. Bruckelmyer
v. Ground Heaters, Inc., 445 F.3d 1374, 1378 (Fed. Cir. 2006).
Appeal 2018-006082
Application 13/524,837

13
35 U.S.C. § 102(b). (Appeal Br. 24; Reply Br. 5–6.11)
We are not persuaded. As the Examiner points out, the transcript
relates to a public meeting of FDA’s Biological Response Modifiers
Advisory Committee, publicly announced via the Federal Register, at which
members of the public were invited to speak. (Ans. 12; FDA Tr. 7:21–8:2.)
The Notice of Meeting in the Federal Register explicitly explained that the
meeting relates to “Rituximab (C2B8 monoclonal antibody), IDEC” and that
IDEC “is seeking an indication for Rituximab as treatment for patients with
relapsed or refractory low grade or follicular B-cell non-Hodgkin’s
Lymphoma.” 62 Fed. Reg. 32619 (1997).
Furthermore, the Notice of Meeting explained that the notice is “given
under the Federal Advisory Committee Act (5 U.S.C. app. 2).” Id. The
Federal Advisory Committee Act (FACA) states that, other than for national
security reasons, “timely notice of each [advisory committee] meeting shall
be published in the Federal Register, and the Administrator shall prescribe
regulations to provide for other types of public notice to insure that all
interested persons are notified of such meeting prior thereto.” Federal
Advisory Committee Act, 5 U.S.C. App 2 § 10(a)(2).
Given FACA’s intent to provide notice of advisory committee
meetings to “all interested persons,” and given that an interested member of
the public unaffiliated with the sponsor of rituximab in fact spoke at the
meeting pursuant to the Federal Register notice (FDA Tr. 7:23–8:9, 15:6–
10), we find a prima facie case exists that an ordinarily skilled artisan for

11 Appellant’s Reply Brief does not include page numbers. Therefore, we
refer to page numbers in the Reply Brief as if the Reply Brief was numbered
sequentially starting with the first page.
Appeal 2018-006082
Application 13/524,837

14
purposes of the claimed invention (e.g., an oncologist or a medical
researcher of average experience) would have been aware of the Biological
Response Modifiers Advisory Committee meeting regarding rituximab.
As to the public accessibility of the transcript, we note that FACA
states that, “[e]xcept where prohibited by contractual agreements entered
into prior to the effective date of this Act, agencies and advisory committees
shall make available to any person, at actual cost of duplication, copies of
transcripts of agency proceedings or advisory committee meetings.” Id. at
§ 11(a). FACA additionally states:
(b) Subject to section 552 of Title 5, United States Code, the
records, reports, transcripts, minutes, appendixes, working
papers, drafts, studies, agenda, or other documents which were
made available to or prepared for or by each advisory
committee shall be available for public inspection and copying
at a single location in the offices of the advisory committee or
the agency to which the advisory committee reports until the
advisory committee ceases to exist.

(c) Detailed minutes of each meeting of each advisory
committee shall be kept and shall contain a record of the
persons present, a complete and accurate description of matters
discussed and conclusions reached, and copies of all reports
received, issued, or approved by the advisory committee. The
accuracy of all minutes shall be certified to by the chairman of
the advisory committee.
Id. at §§ 10(b)–(c) (emphasis added).
In short, there is evidence that an FDA advisory committee meeting
about rituximab was advertised in the Federal Register in June 2016, that a
meeting was held in July 1997, that a transcript of the meeting was
generated and was available to the public in the FDA reading room by
August 8, 1997, prior to the critical date, and that there is a reasonable
Appeal 2018-006082
Application 13/524,837

15
expectation, if not a legal requirement, that transcripts of FDA advisory
committee meetings would be publicly available at a designated place at the
agency. We find based on the above that there is sufficient evidence that an
interested and ordinarily skilled artisan would have been able to locate the
FDA Transcript through the exercise of reasonable diligence more than one
year before the critical date, such that the burden is shifted to Appellant to
demonstrate that the transcript was not available to or accessible by the
public to a sufficient extent. Appellant has provided no persuasive evidence
to this effect. Accordingly, we agree with the Examiner that the FDA
Transcript was a printed publication for purposes of 35 U.S.C. § 102(b).12
Motivation to Combine and Reasonable Expectation of Success
Appellants argue that, even if the FDA Transcript were a printed
publication, the FDA Transcript “would not have motivated [a person of
ordinary skill in the art] to increase the initial infusion rate of subsequent
infusions on days 8, 15, and 22 above 50 mg/h” rather than using the same

12 We acknowledge that the panel in IPR2017-01094 found that petitioner
had not shown that the FDA Transcript was a printed publication. In that
case, however, Petitioner did not cite to publication of the Notice of Hearing
in the Federal Register, attendance of the hearing by an interested member of
the public pursuant to the notice, or the requirements of FACA in support of
the public accessibility of the FDA Transcript. These arguments were thus
not before the panel in IPR2017-01094 and were not discussed in the panel’s
decision denying institution. As discussed, we find that evidence, including
the evidence cited above, suffices to establish a prima facie case that the
FDA Transcript is a printed publication within the meaning of §
102(b). Appellant has not provided persuasive countervailing evidence that
a skilled artisan would not be able to locate the FDA Transcript using
reasonable diligence. Accordingly, on review of the entirety of record we
find that a preponderance of evidence supports the finding that the FDA
Transcript is a printed publication.
Appeal 2018-006082
Application 13/524,837

16
50 mg/h rate for the infusions on each of days 1, 8, 15, and 22. (Appeal Br.
20.)
We are not persuaded. The FDA Transcript teaches administering
rituximab to treat patients with relapsed or refractory low-grade or follicular
B-cell non-Hodgkin’s lymphoma, where rituximab is administered at 375
mg/m2 by intravenous infusion given once weekly times four. (See, e.g.,
FDA Transcript 16:15–18, 18:16–21, 35:19–25, 36:20–24, 79:1–4, and
87:23–88:2.) Moreover, while the FDA Transcript does not specifically
teach treating patients with rituximab using an initial infusion rate of greater
than 50 mg/hour on day 8, 15, 22 if no toxicity was seen on day 1 of
treatment, it teaches that rituximab was “administered . . . at an initial
intravenous rate of 50 mg/hour and increased to a maximal rate of 150
mg/hour” and that “the majority of the adverse events . . . occur with the first
infusion, and subsequent infusions are characterized by much lower
incidence of adverse events.” (FDA Tr. 29:5–8, 13–14; 32:23–33:3; 86:16–
22, and 91:10–13.) The Examiner asserts that, in light of the above, the
limitation regarding increasing the infusion rate during subsequent infusions
would have been obvious to a skilled artisan because “increasing the
infusion rate results in a faster treatment for the patient.” (Ans. 6–7.)
We agree that the Examiner has established a prima facie case of
obviousness with respect to the limitation. As our reviewing court has
explained
an implicit motivation to combine exists not only when a
suggestion may be gleaned from the prior art as a whole, but
when the “improvement” is technology-independent and the
combination of references results in a product or process that is
more desirable, for example because it is stronger, cheaper,
cleaner, faster, lighter, smaller, more durable, or more efficient.
Appeal 2018-006082
Application 13/524,837

17
Because the desire to enhance commercial opportunities by
improving a product or process is universal—and even
common-sensical— . . . there exists in these situations a
motivation to combine prior art references even absent any hint
of suggestion in the references themselves. In such situations,
the proper question is whether the ordinary artisan possesses
knowledge and skills rendering him capable of combining the
prior art references.
Dystar Textilfarben Gmbh & Co. Deutschland KG v. C.H. Patrick Co., 464
F.3d 1356, 1368 (Fed. Cir. 2006). Here, the Examiner has explained that a
faster infusion rate would result in a faster (and presumably more efficient)
treatment process for the patient. Likewise, because the FDA Transcript
explicitly teaches infusion rates of up to 150 mg/hr and that most of the
adverse events occur during the first infusion, the evidence supports a
finding that a skilled artisan would be capable of combining the teachings in
the FDA Transcript to begin the infusion rate at 50 mg/hr but increase the
infusion rate during subsequent infusions.
Appellant relies largely on the Second Levy Declaration13 in arguing
that the FDA Transcript would not have provided a motivation or reasonable
expectation of success in arriving at the claimed invention. In his
declaration, Dr. Levy states that a skilled artisan at the time of invention
would have understood that (1) “infusion reactions can occur with rituximab
infusions”; (2) “[h]igher infusion speeds increase the risk of the adverse
events because more rituximab is present in the body . . . in a shorter
window of time”; and (3) “a severe infusion-related adverse event cause[d]

13 Declaration of Ronald Levy under 37 C.F.R. § 1.132 (April 11, 2017)
(“Second Levy Declaration”).
Appeal 2018-006082
Application 13/524,837

18
by adaptive immunity is more likely to occur in subsequent infusions
compared to the first infusion.” (Second Levy Decl. ¶¶ 7–12.)
Dr. Levy states that, in fact, in the rituximab clinical trials some
patients had adverse events on subsequent infusions without having had an
adverse event in during the first infusion, and prescribing information for
other therapeutic antibodies at the time of the invention allowed rate increase
during the first infusion while the initial rate remained constant for
subsequent infusions. (Id. ¶¶ 13, 15.) Accordingly, Dr. Levy opined that,
because “much was still unknown about the safety of rituximab infusions,” a
skilled artisan “would not [have been] motivated or have [had] a reasonable
expectation of safety for starting rituximab infusion rates faster in
subsequent infusions,” and “the FDA Transcript disclosure that the rate of
infusion was increased during the course of each infusion and fewer adverse
events were seen with subsequent infusions would not render obvious the
inventive concept that rituximab could be infused at a higher initial rate on
subsequent infusions.” (Id. ¶¶ 14, 16.)
We are not persuaded. As an initial matter, in the First Levy
Declaration Dr. Levy explained that a skilled artisan would have understood
McLaughlin’s disclosure that “[t]he initial infusion rate was 50 mg/h, with
subsequent infusion rate increase if no toxicity was seen” to mean that
infusion rate was increased in subsequent infusions rather than that the
infusion rate was increased during the course of each infusion. (First Levy
Decl. ¶ 11.) Dr. Levy does not explain why a skilled artisan would read the
FDA Transcript’s disclosure of increasing infusion rate differently, i.e., that
Appeal 2018-006082
Application 13/524,837

19
the rate was increased during the course of each infusion rather than
increased in subsequent infusions.14
Furthermore, even assuming that the FDA Transcript only disclosed
increasing infusion rate during the course of each infusion, “[o]nly a
reasonable expectation of success, not absolute predictability, is necessary
for a conclusion of obviousness.” In re Longi, 759 F.2d 887, 897 (Fed. Cir.
1985). Likewise, “a given course of action often has simultaneous
advantages and disadvantages, and this does not necessarily obviate
motivation to combine.” Medichem, S.A. v. Rolabo S.L., 437 F.3d 1157,
1165 (Fed. Cir. 2006). Rather, “‘the benefits, both lost and gained, should
be weighed against one another.’” Id. (quoting Winner Int’l Royalty Corp. v.
Wang, 202 F.3d 1340, 1349 n.8 (Fed. Cir. 2000)). For instance, although the
FDA Transcript describes various adverse events that occurred with
treatment using rituximab, the Biological Response Modifiers Advisory
Committee was unanimous in finding the risks of rituximab therapy to be
acceptable given the efficacy data. (FDA Tr. 104:14–23.)
In this case, while we acknowledge Dr. Levy’s statement that higher
infusion rate generally increase the likelihood of adverse events, the FDA
Transcript teaches administering rituximab at an infusion rate as high as 150

14 Appellant cites to paragraph 6 of the Second Levy Declaration as support
that “the FDA Transcript teaches that the initial infusion rate remained 50
mg/hour on the subsequent infusions.” (Appeal Br. 22.) The only evidence
that Dr. Levy cites to for support of this statement, however, is the
Examiner’s February 22, 2017 Non-Final Rejection (“Non-Final Act.”).
(Second Levy Decl. ¶ 6.) We note that the Examiner did not state that “the
FDA Transcript teaches that the initial infusion rate remained 50 mg/hour on
the subsequent infusions,” merely that the FDA Transcript “does not
specifically teach that the initial infusion rate on days 8, 15, 22 was greater
than 50 mg/hour.” (Non-Final Act. 5 (emphasis added).)
Appeal 2018-006082
Application 13/524,837

20
mg/hour without teaching that increasing the infusion rate resulted in
unacceptable safety concerns. Indeed, the FDA Transcript teaches that
rituximab “is safe with limited adverse events.” (FDA Tr. 25:10.) Likewise,
although we acknowledge Dr. Levy’s statement that certain types of adverse
events are more likely in subsequent infusions than the initial infusion, the
FDA Transcript teaches that, at least with respect to rituximab, most of the
adverse events occurred during the initial infusion. Finally, while Dr. Levy
cites to prescription information relating to other therapeutic antibodies that
increased the rate during a first infusion but does not start a subsequent
infusion at a higher initial infusion rate, Dr. Levy does not provide a
persuasive explanation as to why this renders alternative administration
schedule for rituximab non-obvious, given the specific teachings in the FDA
Transcript regarding rituximab. Indeed, the evidence would appear to
support a conclusion that infusion rate is a known result-effective variable,
and “discovery of an optimum value of a result effective variable in a known
process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272,
276 (CCPA 1980).
In short, taking all of the evidence into account, we are not persuaded
by Dr. Levy’s conclusion that “the FDA Transcript[’]s disclosure that the
rate of infusion was increased during the course of each infusion and fewer
adverse events were seen with subsequent infusions would not render
obvious the inventive concept that rituximab could be infused at a higher
initial rate on subsequent infusions.” (Second Levy Decl. ¶ 16.)
Accordingly, we affirm the Examiner’s rejection of claims 15–17 as
obvious over the FDA Transcript. Because we rely on evidence not
Appeal 2018-006082
Application 13/524,837

21
expressly recited by the Examiner, however, we designate the affirmance as
a new ground of rejection.
SUMMARY
In summary, we reverse the Examiner’s rejection of claims 15–17 as
anticipated by the November 1997 prescribing information for RITUXAN®.
We affirm the Examiner’s rejection of claims 15–17 as obvious over
the FDA Transcript but designate our affirmance as a new ground of
rejection.
TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to
37 C.F.R. § 41.50(b). Section 41.50(b) provides “[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.” Section 41.50(b) also provides:
When the Board enters such a non-final decision, the
appellant, within two months from the date of the
decision, must exercise one of the following two options
with respect to the new ground of rejection to avoid
termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence
relating to the claims so rejected, or both, and have the
matter reconsidered by the examiner, in which event the
prosecution will be remanded to the examiner. The new
ground of rejection is binding upon the examiner unless
an amendment or new Evidence not previously of Record
is made which, in the opinion of the examiner,
overcomes the new ground of rejection designated in the
decision. Should the examiner reject the claims, appellant
may again appeal to the Board pursuant to this subpart.
Appeal 2018-006082
Application 13/524,837

22
(2) Request rehearing. Request that the proceeding
be reheard under § 41.52 by the Board upon the same
Record. The request for rehearing must address any new
ground of rejection and state with particularity the points
believed to have been misapprehended or overlooked in
entering the new ground of rejection and also state all
other grounds upon which rehearing is sought.
Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure § 1214.01.
No time period for taking subsequent action in connection with this
appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED; 37 C.F.R. § 41.50(b)