Ex Parte Geraghty et al

Patent Trial and Appeal Board

Feb 5, 2015

12064537 (P.T.A.B. Feb. 5, 2015)

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.
12/064,537 07/03/2008 Daniel E. Geraghty 9498-3 1707
20792 7590 02/05/2015
MYERS BIGEL SIBLEY & SAJOVEC
PO BOX 37428
RALEIGH, NC 27627
EXAMINER
SCHWADRON, RONALD B
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
02/05/2015 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte DANIEL E. GERAGHTY and NI LEE
_________

Appeal 2012-008293
Application 12/064,537
Technology Center 1600
__________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.

PAULRAJ, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a
monoclonal antibody that specifically binds to the cell surface HLA-F
histocompatibility protein of activated mammalian T-lymphocytes. The
Examiner rejected the claims on obviousness grounds. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.

1 Appellants identify the Real Party in Interest as Fred Hutchinson Cancer
Research (see App. Br. 3).
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STATEMENT OF THE CASE
Background
“Recent work using new monoclonal antibodies reactive with HLA-F
showed that while HLA-F was not surface expressed on most cell lines that
contained intracellular protein, HLA-F was expressed on the surface of B
cell and some monocyte cell lines and in vivo on extravillous trophoblasts
that had invaded the maternal decidua . . .” (Spec. 1). The invention
described in the Specification relates to an antibody that “specifically binds
to the cell surface HLA-F histocompatibility protein of activated mammalian
T-lymphocytes, and which antibody does not bind to the-cell surface of non-
activated mammalian T-lymphocytes” (id. at 2). According to the
Specification, “[a]n advantage of the present invention is that HLA-F is only
expressed on the cell surface of activated immune cells such as activated
CD4 and CD8 T cells, and not on the surface of cells such as CD4+ CD25+
regulatory T cells, nor on the surface of CD21, CD33, or CD44 cells,” and
“[h]ence these latter cells are not bound, removed and/or depleted by the
methods of the present invention as they are with, for example, by methods
utilizing anti-CD25+ antibodies” (id. at 3).
The Claims
Claims 37–39 are under appeal. Independent claim 37 is
representative, and reads as follows:
37. A monoclonal antibody that specifically binds to the cell surface
HLA-F histocompatibility protein of activated mammalian T-lymphocytes,
and which antibody does not bind to the cell surface of non-activated
mammalian T-lymphocytes;
said antibody selected from the group consisting of human
monoclonal antibodies and chimeric monoclonal antibodies, said chimeric
monoclonal antibodies having a human immunoglobulin constant region.

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The Rejection

The Examiner rejected the claims under 35 U.S.C. § 103(a) as being
unpatentable over the combination of Kohji2 and Lonberg.3

FINDINGS OF FACT
We adopt the Examiner’s findings of fact as set forth in the Answer.
We highlight the following for emphasis.
FF1. Lonberg teaches:
One of the major impediments facing the development
of in vivo applications for monoclonal antibodies in
humans is the intrinsic immunogenicity of non-human
immunoglobulins. Patients respond to therapeutic doses
of rodent monoclonal antibodies by making antibodies
against the rodent immunoglobulin sequences. These
human anti-mouse antibodies (HAMA) neutralize the
therapeutic antibodies and can cause acute toxicity. The
MAMA [sic, HAMA] response is less dramatic in
immunodeficient patients. Therefore, intrinsic
immunogenicity has not prevented the use of rodent
monoclonal antibodies for the treatment of graft
rejection, which involves the temporary attenuation of
the patient’s immune response. Rodent antibodies may
also be useful for treating certain lymphomas that involve
immunodeficiencies. However, even immunodeficient
patients can mount a HAMA response which leads to a
reduction in safety and efficacy.

(Lonberg, col. 1 ll. 25–42.)

2 Kohji et al., JP 2003-012544, published Jan. 2003 (machine translation
relied upon) (hereinafter “Kohji”).
3 Lonberg et al., US 5,633,425, issued May 27, 1997 (hereinafter
“Lonberg”).
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FF2. Lonberg teaches:
Based on the foregoing, it is clear that a need exists
for heterologous monoclonal antibodies, e.g. antibodies
of human origin, derived from a species other than
human. Thus, it is an object of the invention herein to
provide a source of monoclonal antibodies that may be
used therapeutically in the particular species for which
they are designed.

(Id., col. 3 ll. 20–25.)
FF3. Kohji teaches cancer treatment using an “anti-HLA-F-antibody”
showing “strong reactivity to [the] cancer specific antigen HLA-F”
(Kohji, machine translation, ¶¶ 32, 63). Kohji exemplifies the
production of an anti-HLA-F mouse monoclonal antibody (id., ¶
55).

ANALYSIS
The Examiner finds that Kohji “teaches a monoclonal antibody
against HLA-F, a pharmaceutical composition of said antibody and said
antibody attached to a cytotoxic moiety,” and that Lonberg teaches “methods
of making human monoclonal antibodies against a desired antigen and the
advantages of such antibodies for therapeutic purposes” (Ans. 5). Based on
these teachings, the Examiner concludes that “[i]t would have been prima
facie obvious to one of ordinary skill in the art at the time the invention was
made to have created the claimed invention” (id.).
Based on the cited teachings of the prior art, we determine that a
prima facie showing of obviousness has been made. In particular, we
conclude that a skilled artisan would have found it desirable to create a
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human anti-HLA-F monoclonal antibody in order to minimize the acute
toxicity associated with a HAMA response for the murine antibodies taught
by Kohji (FF1–3). We have considered Appellants’ arguments, but are not
persuaded otherwise.
Appellants argue that “Kohji et al. published more than five and a
half years after Lonberg et al.,” and “[t]he lack of any teaching or
suggestion after this length of time is contrary to the Examiner’s assertions
in regard to obviousness” (Br. 7). We are not persuaded. “The mere age of
the references is not persuasive of the unobviousness of the combination of
their teachings, absent evidence that, notwithstanding knowledge of the
references, the art tried and failed to solve the problem.” In re Wright, 569
F.2d 1124, 1127 (CCPA 1977) (100 year old patent was properly relied upon
in a rejection based on a combination of references.). Federal Circuit
“precedent requires that the applicant submit actual evidence of long-felt
need, as opposed to argument. This is because ‘[a]bsent a showing of long-
felt need or the failure of others, the mere passage of time without the
claimed invention is not evidence of nonobviousness.’” In re Kahn, 441
F.3d 977, 990 (Fed. Cir. 2006) (citations omitted). Here, Appellants have
not demonstrated why a five and a half year span between the publications
of the Kohji and Lonberg references is sufficient to establish a “long-felt but
unsolved need” for the claimed invention.
Appellants argue that “Kohji et al. provide[s] no teaching or
suggestion to modify their antibodies to arrive at the claimed antibody or to
modify their antibodies in any other manner” (Br. 7). We are not persuaded.
The requisite motivation for creating human anti-HLA-F antibodies comes
from the desire to avoid a toxic HAMA response, as taught by Lonberg
(FF1).
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Appellants argue that “Lonberg et al. teach that production of a human
antibody ‘requires that the heterologous immunoglobulin transgenes
contained within the transgenic animal function correctly throughout the
pathway of B-cell development,” and that neither Lonberg nor Kohji provide
any guidance for meeting this requirement for anti-HLA-F antibodies (Br.
7). We are not persuaded. Lonberg teaches “methods for producing
heterologous antibodies in a transgenic animal containing primary repertoire
B-cells having rearranged heavy and light heterologous immunoglobulin
transgenes” (Lonberg, col. 5 ll. 54–57). Lonberg further teaches that
[I]n the preferred embodiments, gene segments are
derived from human beings. The transgenic non-human
animals harboring such heavy and light transgenes are
capable of mounting an Ig-mediated immune response to
a specific antigen administered to such an animal. B-
cells are produced within such an animal which are
capable of producing heterologous human antibody.
After immortalization, and the selection for an
appropriate monoclonal antibody (Mab), e.g. a
hybridoma, a source of therapeutic human monoclonal
antibody is provided. Such human Mabs have
significantly reduced immunogenicity when
therapeutically administered to humans.

(Id. at col. 13 l. 65–col. 14 l. 9.) Lonberg further teaches that “[e]xamples of
antigens which may be used to generate heterologous antibodies in the
transgenic animals of the invention containing human immunoglobulin
transgenes include bacterial, viral and tumor antigen as well as particular
human B- and T-cell antigens associated with graft rejection or
autoimmunity” (id. at col. 14 ll. 10–15). We therefore find that Lonberg
provides sufficient guidance for a skilled artisan to make a human anti-HLA-
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F antibody through the pathway of B-cell development. Appellants do not
provide any evidence to the contrary.
Appellants assert that “Lonberg et al. do not teach that all non-human
antibodies need to be made into human antibodies, even if they are to be
used for therapeutic purposes,” and “[i]nstead, Lonberg et al. state that
rodent antibodies can be useful in the treatment of graft rejection and certain
lymphomas. See, Lonberg et al., col. 1, lines 34-39” (Br. 8). In support,
Appellants present a “List of Monoclonal Antibodies” printed from
Wikipedia as evidence. We are not persuaded. Even assuming that rodent
antibodies may be used for some therapeutic purposes, Appellants do not
specifically address the motivation to avoid a HAMA response for the
murine anti-HLA-F antibodies taught by Kohji. For example, Appellants do
not present any evidence suggesting that a HAMA response would not be
considered an issue for such murine anti-HLA-F antibodies. Further, even if
non-human antibodies had therapeutic effect, we have already noted that
Lonberg teaches that human Mabs reduce immunogenicity during
therapeutic administration, a specific and cogent reason for modifying the
murine anti-HLA-F antibody with the appropriate human components.
We therefore affirm the obviousness rejection of claim 37 based on
Lonberg and Kohji. Appellants have not separately argued dependent claims
38 and 39, and therefore those claims fall with claim 37. 37 C.F.R.
§ 41.37(c)(1)(vii).
SUMMARY
We affirm the rejection under 35 U.S.C. § 103(a).

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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

cdc