Ex Parte Bluth

Board of Patent Appeals and Interferences

Dec 1, 2008

10426334 (B.P.A.I. Dec. 1, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MARTIN HEATH BLUTH
__________

Appeal 2008-4651
Application 10/426,334
Technology Center 1600
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Decided: December 1, 2008
__________

Before TONI R. SCHEINER, ERIC GRIMES, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treatment of a patient with recombinant Fc fragments. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.

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Application 10/426,334

Background
“Immunoglobulin treatment has been used extensively for the
treatment of multiple disease states in patients, including autoimmune
diseases” (Spec. 1:9-10). The Specification notes that “immunoglobulin
treatments may require that only a certain class or classes of molecule be
given. However, with an immunoglobulin preparation derived from human
donor serum, other classes of immunoglobulin are likely present” (Spec.
1:25-27). According to the Specification, “administering the Fcγ portion of
the immunoglobulin molecule was found to be an effective treatment for
immune thrombocytopenia” (Spec. 2:9-10).
Statement of the Case
The Claims
Claims 1-5, 9-11, 18-21, and 28 are on appeal.1 We will focus on
claim 1, which is representative and reads as follows:

1. A method for treatment of a patient, the method
comprising the steps of:
obtaining recombinant Fc fragments; and
providing the recombinant Fc fragments for treatment
of the patient.

The prior art
The Examiner relies on the following prior art references to show
unpatentability:
Debré et al., Infusion of Fcγ fragments for treatment of children with
acute immune thrombocytopenic purpura, 342 Lancet 945-949 (Oct. 1993).

1 The Examiner withdrew claims 6-8, 12-17, and 22-27 as drawn to
nonelected inventions (Ans. 2).
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Jendeberg et al., Engineering of Fc1 and Fc3 from human
immunoglobulin G to analyse subclass specificity for staphylococcal protein
A, 201 J. Immunological Methods 25-34 (1997).

The issues
The rejections as presented by the Examiner are as follows:
A. Claims 1-3, 9-11, and 28 stand rejected under 35 U.S.C. § 112, second
paragraph as indefinite (Ans. 3).
B. Claims 1-5, 9-11, 18-21, and 28 stand rejected under 35 U.S.C. §
102(b) as being anticipated by Debré (Ans. 4).
C. Claims 1-5, 9-11, 18-21, and 28 stand rejected under 35 U.S.C. §
103(a) as being obvious over Debré and Jendeberg (Ans. 5).
A. 35 U.S.C. § 112, second paragraph rejection
The Examiner concludes that
Claims 1-3, 9-11, and 28 are indefinite in the recitation of “a
method of treatment of a patient” because the metes and
bounds of the “a patient” population are not clear and
ambiguous. The “patient” population is not defined by the
claims and the specification does not provide a standard for
ascertaining the nature or parameters of the “patient”.

(Ans. 3.)
Appellant “submits that the word ‘patient,’ as used in the claims
would be clearly understood by one having skill in the art to refer to the
plain meaning of the word ‘patient;’ i.e., one to whom a clinician is
administering treatment” (App. Br. 6).
In view of these conflicting positions, we frame the indefiniteness
issue before us as follows:
Is the word “patient” vague and indefinite?
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A. Discussion of the 35 U.S.C. § 112, second paragraph rejection
We agree with Appellant that the skilled artisan understands the
meaning of the word “patient.” We think that the term “patient” is broad
and may include individuals afflicted with a disease and “normal”
individuals. The Examiner’s concern that “the instant claims do not
correspond in scope with the claimed invention” is not properly addressed
under the second paragraph of 35 U.S.C. § 112.
We reject the Examiner’s statement that “a person of ordinary skill in
the art cannot translate” the definition of patient “into meaningfully precise
claim scope” (Ans. 7). In our opinion, any person of ordinary skill would
reasonably understand what the word “patient” means in the context of a
treatment method using Fc fragments. The Examiner is equating the breadth
of the claim with indefiniteness. However, “breadth is not to be equated
with indefiniteness.” In re Miller, 441 F.2d 689, 693 (CCPA 1971).
We reverse the rejection of claims 1-3, 9-11, and 28 under 35 U.S.C. §
112, second paragraph.
B. 35 U.S.C. § 102(b) rejection over Debré
The Examiner finds that “Debré . . . teach [a] method for treatment of
children suffering from ITP with intravenous infusion of Fc fragments
isolated from IgG” (Ans. 4). The Examiner contends that “Appellant has not
provided any objective evidence to distinguish the Fc fragments of the prior
art teachings of Debré et al. and that produced recombinantly. Also note the
claims do not recite distinguishing characteristics of the Fc fragments and
the claims do not set forth recombinant method steps” (Ans. 8).
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Appellant argues that “Debré does not disclose or remotely address
the use of recombinant Fc fragments in the disclosed treatment of ITP, as
explicitly required by the subject claims” (App. Br. 8). Appellant “submits,
however, that claims 1, 18 and 28 are directed toward methods for treatment
of a patient; these claims do not define a product at all. Clearly, they do not
define a product by the process steps by which the product is made and are
thus not product-by-process claims” (App. Br. 8).
Appellant further contends that “there are marked differences between
products derived from enzymatically altered human sources (as in Debré)
verses [sic] those agents derived from recombinant methods (as claimed)
which impact structure and function” (App. Br. 9).
In view of these conflicting positions, we frame the anticipation issue
before us as follows:
Has Appellant established that the Fc fragments used in the claimed
method are distinguishable from the Fc fragments used in Debré’s method?
Findings of Fact (FF)
1. Claim 1 is drawn to a method using “recombinant Fc
fragments” themselves.
2. Debré teaches “the clinical and biological effects of infusion of
purified Fcγ fragments in children with previously untreated ITP [immune
thrombocytopenic purpura]” (Debré 945, col. 2). Debré teaches that “Fcγ
fragments were prepared at Pasteur Merieux Serums & Vaccins” (Debré
946, col. 1).
3. Debré teaches that the “purified Fcγ fragments contained no
detectable Fab, less than 2% residual IgG, and less than 4% Fab/c (IgG
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containing only one Fab linked to the Fc region). They had no
anticomplementary activity . . . and their expected in-vivo half-life was 6-10
days” (Debré 946, col. 1).
4. Debré teaches that “Fcγ fragment preparations were first given
in a phase I study with no adverse reaction to six healthy adult volunteers at
bolus doses ranging from 10 mg to 1000 mg daily” (Debré 946, col. 1).
5. Debré teaches that “[e]leven of the twelve children treated with
Fcγ fragments in this study showed rises in platelet counts . . . at rates too
high for spontaneous remission” (Debré 948, col. 1).
B. Discussion of the U.S.C. § 102(b) rejection over Debré
We agree with Appellant (App. Br. 8) that while Debré clearly
teaches a method of treatment of a patient comprising obtaining Fc
fragments (FF 1-3) and providing the Fc fragments for treatment of the
patient (FF 4-5), Debré does not teach the use of “recombinant” Fc
fragments (FF 3). The Fcγ fragments of Debré are made using standard
purification techniques from human sources (FF 2-3) and are therefore not
“recombinant”.
However, the Examiner contends that
[T]he purification or production of a protein by a particular
process does not impart novelty or unobviousness to a
protein when the same protein is taught by the prior art. This
is particularly true when the properties of the protein (e.g.
antibodies or immunoglobulins or Fc gamma fragments) are
not changed by the process in an unexpected manner.
Therefore, even if a particular process used to prepare a
protein is novel and unobvious over the prior art, the protein
per se, even when limited to a particular process is
unpatentable over the same protein taught by the prior art.

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(Ans. 11.) Appellant responds that “[i]t is well-established law that ‘[p]ure
materials are novel vis-a-vis less pure or impure materials because there is a
difference between pure and impure materials.’ See, e.g., In re Bergstrom,
427 F.2d 1394, 166 USPQ 256 (CCPA 1970)” (Rep. Br. 5).
In our opinion, both the Examiner and Appellant properly state the
law, but differ in their interpretation of what is taught in Debré. If the Fc
fragments of Debré are identical to Fc fragments made by “recombinant”
technology as asserted by the Examiner, then the method of claim 1 is
inherently anticipated by Debré.
Debré teaches that the “purified Fcγ fragments contained no
detectable Fab, less than 2% residual IgG, and less than 4% Fab/c (IgG
containing only one Fab linked to the Fc region)” (Debré 946, col. 1). We
conclude that in teaching that there no detectable Fab, but separately stating
that there was less than 2% residual IgG and less than 4% residual Fab/c,
Debré taught that while the composition may have entirely lacked Fab, the
composition had detectable amounts of residual IgG and Fab/c that were
lower than the stated thresholds (FF 4).
However, we are persuaded by the Examiner’s argument that “[e]ven
if the method of purifying Fcγ fragments by Debre . . . may result in certain
impurity of product, it does not change the fact that the recombinantly made
Fcγ fragments have the same properties and molecular structure as the prior
art Fcγ fragments. . . . [T]he burden falls on Appellant to demonstrate that
the claimed products differ from the prior art” (Ans. 11). This indirect
reference to In re Best, 562 F.2d 1252 (CCPA 1977) is persuasive. We
recognize that Debré’s composition containing the Fc fragments is likely
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different from a composition of Fc fragments made recombinantly, but the
claim is drawn to the use of Fc fragments themselves, not the compositions
comprising them (FF 4). Appellant has provided no evidence on this record
that there is any structural or functional difference between Debré’s Fc
fragments and the instant recombinant fragments.
We therefore find that Debré does inherently anticipate the claim and
we affirm the rejection of claim 1 under U.S.C. § 102(b) over Debré.
Pursuant to 37 C.F.R. § 41.37(c)(1)(vii)(2006), we also affirm the rejection
of dependent claims 2-5, 9-11, 18-21, and 28.
C. 35 U.S.C. § 103(a) rejection over Debré and Jendeberg
The Examiner argues that
The rationale to support a conclusion that the claims would
have been obvious is that all the claimed elements (methods
of treating ITP by administering Fc fragments effectively
taught by Debre et al. and obtaining Fc fragment
recombinantly taught by Jendeberg et al. for large scale
production of serum free proteins for therapy) were known
in the prior art and one skilled in the art could have
combined the elements as claimed by known methods with
no change in the Fc fragments[’] respective functions, and
the combination would have yield[ed] nothing more than
predictable results of method of treating patients suffering
from ITP effectively to one of ordinary skill in the art at the
time the invention.

(Ans. 14).
Appellant “submits that Debré contains no teaching or suggestion
regarding the use of recombinant Fcγ fragments in its method of treatment
and Jendeberg contains no teaching or suggestion regarding the use of its
recombinant Fcγ fragments in a method of treatment” (App. Br. 14).
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Appellant further argues that “the Affidavit Under 37 C.F.R. §1.132 filed
with Appellant's response of September 5, 2006, at paragraphs 15-20, recites
a number of non-obvious and unexpected results obtained from aspects of
the claimed invention as compared with the conventional therapeutic
techniques taught by Debré” (App. Br. 16). Appellant also contends that
“Debré’s teaching away is supported by the fact that Debré does not suggest
a desirability for further purification” (App. Br. 17).
In view of these conflicting positions, we frame the obviousness issue
before us as follows:
Would it have been prima facie obvious to obtain Fc fragments
necessary for the treatment method of Debré by recombinant expression of
Fc fragments as taught by Jendeberg?
Findings of Fact
6. Jendeberg teaches a “system for production of recombinant Fc
fragments of human IgG in Escherichia coli has been developed”
(Jendeberg, abstract).
7. Jendeberg teaches that “[t]here are several reasons to develop
an expression system for recombinant Fc fragments (Jendeberg 27, col. 1).
8. Jendeberg teaches that “the described expression system has
proven efficient for the production of both wild-type and engineered Fc
fragments” (Jendeberg 33, col. 1).
C. Discussion of the U.S.C. § 103(a) rejection over Debré and Jendeberg
We conclude that the Examiner has set forth a prima facie case that
claim 1 would have been obvious to the ordinary artisan in view of Debré
and Jendeberg. In KSR, the Supreme Court indicated that “[w]hen a work is
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available in one field of endeavor, design incentives and other market forces
can prompt variations of it, either in the same field or a different one. If a
person of ordinary skill can implement a predictable variation, §103 likely
bars its patentability.” KSR Int’l v. Teleflex Inc., 127 S. Ct. 1727, 1740
(2007).
In the instant case, the use of the efficient recombinant expression
system of Jendeberg (FF 6, 8) to produce Fc fragments for the therapeutic
treatments using Fc of Debré (FF 1-5), represents a predictable approach that
the ordinary practitioner would apply to obtain Fc fragments for the
treatment of Debré. Such a combination is merely a “predictable use of
prior art elements according to their established functions.” KSR, 127 S. Ct.
at 1740.
Appellant argues that the combination of Debré and Jendeberg is
unobvious because “the Examiner has failed to identify any objective
evidence of record which supports the proposed combination” (App. Br. 14).
In fact, the teaching of Jendeberg that recombinant systems provide efficient
production of Fc fragments (FF 8) provide motivations to use Jendeberg’s
recombinant expression system to obtain Fc fragments for Debré’s
therapeutic method (FF 4-5).
Appellant also argues that the method has unexpected results (App.
Br. 16). We have reviewed the Bluth Affidavit filed September 8, 2006.
We are not persuaded that this affidavit identifies any unexpected results.
Bluth states that “human plasma-derived components . . . are not risk free.
Reported side effects include, anaphylaxis in IgA deficient patients. . . .
Moreover, since IVIG, and derived Fcγ fragments are obtained from a
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pooled human donor serum product, it has the undesirable potential to
transmit infections . . . such as heptatitis C” (Bluth Dec. ¶ 17). However, as
demonstrated by the references cited by Dr. Bluth, these concerns were well
known to the ordinary practitioner, particularly the concern with regard to
infectious agents in blood products. See Taliani,2 who states “the safety of
IVIG has been questioned because of the possible occurrence of non-A, non-
B hepatitis among treated patients” (Taliani 103, col. 1). Also see Novo
Nordisk Pharmaceuticals, Inc. v. Bio-Technology General Corp., 424 F.3d
1347, 1349 (Fed. Cir. 2005) (“[T]he use of pituitary-derived hGH carried a
high risk of contamination and infection for the patient”).
We conclude that the concerns raised by Dr. Bluth represent issues of
which the ordinary practitioner would have been aware and consequently,
the use of a recombinant expression system to avoid impurities in naturally
obtained products which might cause disease or other sequelae is the
expected result, and does not represent an unexpected result.
We are not persuaded by Appellant’s argument “Debré’s teaching
away is supported by the fact that Debré does not suggest a desirability for
further purification” (App. Br. 17). Like our appellate reviewing court,
“[w]e will not read into a reference a teaching away from a process where no
such language exists.” DyStar Textilfarben GmbH & Co. Deutschland KG v.
C.H. Patrick Co., 464 F.3d 1356, 1364 (Fed. Cir. 2006). There is no
teaching in Debré which teaches away from using recombinant Fc fragments

2 Taliani et al., Hepatitis C virus infection in
hypogammaglobulinemic patients receiving long-term replacement
therapy with intravenous immunoglobulin. 35 Transfusion 103-
107 (1995).
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nor is there any teaching in Debré that further purification is undesirable.
Additionally, there is no teaching in Jendeberg which teaches away from
using recombinant Fc fragments in therapeutic applications such as the
treatment method of Debré.
We also do not find persuasive Appellant’s argument that there is no
disclosure of “the differences between the amino acid composition, three
dimensional structure, receptor-ligand binding characteristics, function-
mechanism relationships, and antigenicity, among other characteristics, of
the Fc fragment agent employed in the Debré treatment method as compared
to recombinant Fc fragments” (Reply Br. 7). The claim is broadly drawn to
a method using any “recombinant” Fc fragments, whether they are identical
in structure to the Fc fragments of Debré or differ from the fragments of
Debré. While there may be some Fc fragments not suggested by Debré, the
scope of the claim reasonably encompasses recombinant Fc fragments
rendered obvious by Debré and Jendeberg.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) over Debré
and Jendeberg. Pursuant to 37 C.F.R. § 41.37(c)(1)(vii)(2006), we also affirm
the rejections of claims 2-5, 9-11, 18-21, and 28 as these claims were not
argued separately.
CONCLUSION
In summary, we reverse the rejection of claims 1-3, 9-11, and 28
under 35 U.S.C. § 112, second paragraph.
We affirm the rejection of claims 1-5, 9-11, 18-21, and 28 under
U.S.C. § 102(b) as anticipated by Debré.
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In addition, we affirm the rejection of claims 1-5, 9-11, 18-21, and 28
under 35 U.S.C. § 103(a) as unpatentable over Debré and Jendeberg.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).
AFFIRMED
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