Ex Parte Hadden

Patent Trial and Appeal Board

Feb 5, 2018

13653152 (P.T.A.B. Feb. 5, 2018)

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.
13/653,152 10/16/2012 John W. Hadden U0157.70014US03 6545
23628 7590 02/07/2018
WOLF GREENFIELD & SACKS, P.C.
600 ATLANTIC AVENUE
BOSTON, MA 02210-2206
EXAMINER
JUEDES, AMY E
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
02/07/2018 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHN W. HADDEN
(APPLICANTS: IRX Therapeutics, Inc.)
Appeal 2016-0033401
Application 13/653,1522
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
JOHN G. NEW, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL
This Appeal3 under 35 U.S.C. § 134(a) involves claims 33—38 and
40-50 (App. Br. 5). Examiner entered a rejection under 35 U.S.C. § 103(a).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Oral hearing held January 30, 2018.
2 Appellant identifies the real party in interest as “IRX Therapeutics, Inc.”
(App. Br. 3).
3 This Appeal is related to Appeal 2016-008344, Application 13/940,558
(see App. Br. 4).
Appeal 2016-003340
Application 13/653,152
STATEMENT OF THE CASE
Appellant’s disclosure “relates to vaccine therapy for cancer patients
. . . . More specifically, [Appellant’s disclosure] . . . relates to a vaccine
immunotherapy that immunizes patients, having immune suppression, to
both endogenous and exogenous tumor peptides or proteins” (Spec.4 1).
33. A method for inducing an immune response to an
exogenous antigen in a subject, the method comprising:
administering an effective amount of a natural cytokine
mixture (NCM) to the subject, wherein the NCM comprises
Interleukin-I (IL-1), Interleukin-2 (IL-2), Interleukin-6 (IL-6),
Interleukin-8 (IL-8), Interleukin-12 (IL-12), Interferon-y (IFN-
y), Tumor necrosis factor-a (TNF-a), Granulocyte colony-
stimulating factor (G-CSF), and Granulocyte macrophage
colony-stimulating factor (GM-CSP);
administering an effective amount of a thymic peptide
selected from the group consisting of thymosin al, thymosin
all, and prothymosin to the subject; and
administering at least one exogenous antigen to the
subject,
wherein an immune response to the at least one
exogenous antigen is induced in the subject; and
wherein the NCM and the at least one exogenous antigen
are administered on the same day to the subject.
(App. Br. 30.)
The claims stand rejected as follows:
Claims 33—38 and 46—50 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over the combination of Hadden ’9835 and Eisenbach.6
4 Appellant’s November 3, 2013 Substitute Specification.
5 Hadden, US 5,632,983, issued May 27, 1997.
6 Eisenbach, et al., WO 00/06723, published Feb. 10, 2000.
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Application 13/653,152
Claims 40-45 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of Hadden ’983, Eisenbach, and Hadden ’94(a).7
Claims 33—38, 40-48, and 50 stand rejected under 35 U.S.C. § 103(a)
as unpatentable over the combination of Hadden ’983, Hadden ’99,8 and
Hadden ’94(b).9
Claims 33—38 and 40-50 stand rejected under the judicially created
doctrine of obviousness-type double patenting as being unpatentable over
the claims of Hadden ’07210 in view of Hadden ’983, Hadden ’94(a), and
Eisenbach.
Claims 33—38 and 40-50 stand rejected under the judicially created
doctrine of obviousness-type double patenting as being unpatentable over
the claims of Hadden ’517* 11 in view of Hadden ’983 and Eisenbach.12
Claims 33—38 and 40-50 stand provisionally rejected under the
judicially created doctrine of obviousness-type double patenting as being
unpatentable over the claims of Hadden ’77913 in view of Hadden ’983 and
Hadden ’94(a).
7 John W. Hadden et al., Interleukins and Contrasuppression Induce Immune
Regression of Head and Neck Cancer, 120 Arch Otolaryngol Head Neck
Surg. 395^103 (1994).
8 J.W. Hadden, The immunology and immunotherapy of breast cancer: an
update, 21 International Journal of Immunopharmacology 79-101 (1999).
9 John W. Hadden, T-Cell Adjuvants, 16 Int. J. Immunopharmac. 703—710
(1994).
10 Hadden, US 6,977,072 B2, issued Dec. 20, 2005.
11 Hadden et al., US 9,492,517 B2, issued Nov. 15, 2016. Examiner refers to
this reference as Application No. 12/274,732 (see Ans. 8).
12 Application 12/274,732 issued as Hadden ’517. Therefore, this rejection
is no longer provisional (cf Ans. 8).
13 Hadden, US 2014/0010779 Al, published Jan. 9, 2014. Examiner refers
to this reference as Application No. 13/940,558 (see Ans. 9).
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Claims 33—38 and 40-50 stand rejected under the judicially created
doctrine of obviousness-type double patenting as being unpatentable over
the claims of Hadden ’79614 in view of Hadden ’983, Hadden ’94(a), and
Eisenbach.
Claims 33—38 and 40-50 stand rejected under the judicially created
doctrine of obviousness-type double patenting as being unpatentable over
the claims of Hadden ’51915 in view of Hadden ’983.16
Obviousness:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Appellant discloses that the art prior to Appellant’s filing date
recognized that a
fundamental problem in the effort to immunize cancer patients
is that the tumor-bearing state is associated with
immunosuppressive mechanisms derived from both the tumor
and the host’s disturbed immune system . . . thereby making
immunization difficult. . . . Immune suppression or depletion
involves a reduced capacity of the immune system to respond.
Such suppression can be drug or disease induced. The
condition can be drug induced by treatment, virus induced as in
14 Hadden, US 8,784,796 B2, issued July 22, 2014. Examiner refers to this
reference as Application No. 13/940,579 (see Ans. 9—10).
15 Hadden et al., US 9,492,519 B2, issued Nov. 15, 2016. Examiner refers to
this reference as Application No. 13/940,635 (see Ans. 10-11).
16 Application 13/940,635 issued as Hadden ’519. Therefore, this rejection
is no longer provisional (cf Ans. 11).
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AIDS, or induced by a disease state such as cancer. The
immune system in this condition is effectively turned off.
(Spec.17 2 (citations omitted).) See Hadden ’983 2: 22—30:
The limited efficacy and significant toxicity associated with
high doses of rIL-2, rIFN-y, rTNF-a, and other monotherapies,
suggests reconsideration of natural combinations of cytokines
in therapeutic strategies. Furthermore, more than one-hundred
different cytokine activities have been identified, which raises
significant doubt as to whether immunotherapy, based upon
combining recombinant cytokines, has a reasonable probability
of success in the cancer clinic in the near future.
See also Hadden ’983 14: 10-12 (exemplifying “chemotherapeutic agents”
as a class of agents that “can damage cells, including T lymphocytes,
involved in the immune response”); cf. Hadden ’983 1: 5—6 (Hadden ’983
“relates to an improved method of treating cellular immune deficiencies”);
Hadden ’983 14: 4—10 (Hadden ’983’s “composition [] potently promotes T
lymphocyte function . . . and development. . ., which is therapeutically
relevant in any therapeutic measures requiring stimulation of the immune
system or restoring even partial functioning of a damaged or defective
immune system”).
FF 2. Appellant discloses a
method for overcoming immune depression by inducing
production of naive T cells and restoring T-cell immunity. That
is, the present invention provides an immune restoration.
[Appellant’s disclosure]. . . further provides a method of
vaccine immunotherapy including the steps of inducing
production of naive T cells and exposing the naive T cells to
endogenous or exogenous antigens at an appropriate site ...[;]
a method for unblocking immunization at a regional lymph
node by promoting differentiation and maturation of immature
dendritic cells at a regional lymph node and allowing
17 Appellant’s November 3, 2013 Substitute Specification.
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presentation of processed peptides by resulting mature dendritic
cells, thus exposing tumor peptides to T cells to gain
immunization of the T cells [; and] a method of treating cancer
and other persistent lesions by administering an effective
amount of a natural cytokine mixture as an adjuvant to
endogenous or exogenously administered antigen of the cancer
or other persistent lesions.
(Spec. 4; cf. Hadden ’983 4: 3—8 (disclosing “a method to treat cellular
immune deficiency in ... a patient by the steps of determining the presence
of a cellular immune deficiency and coadministering to the patient an
effective amount of a thymic peptide such as Thymosin ai combined with an
effective amount of a natural cytokine preparation [(NCM)])”; see Hadden
’983 3: 20-21; see also Hadden ’983 16: 39—52 (disclosing “[a] method of
improving cellular immune response in a patient comprising coadministering
to [a] patient an effective amount of,” i.e., “Thymosin af’ and NCM);
Hadden ’983 1: 8—11 (disclosing that “in recent years it has become possible
to modulate the immune system to improve its response and, where
components of the system are non-functioning, to either partially or
completely restore the function of the component”); Hadden ’983 1: 27—31
(disclosing that “[t]he use of immunomodulators in clinical medicine
includes the reconstitution of immune function (or the correction of
immunodeficiency) and the suppression of normal or excessive immune
function. A major class of immunomodulators is cytokines”); see generally
Ans. 2-3).
FF 3. Appellant’s disclosure
provides for unblocking immunization at a regional lymph node
by promoting differentiation and activation of dendritic cells in
a regional lymph node and thus allowing presentation by
resulting mature dendritic cells of small peptides. . . .
Additionally, induction of mature dendritic cells is required.
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Finally, mobilization of peripheral blood T-lymphocytes in T-
lymphocytopoenic patients in the presence of induction of naive
T cells capable of responding to dendritic cells presenting
endogenous tumor peptides is desired. . . .
[Thus,] the key mechanistic features of [Appellant’s
disclosure] are the in vivo maturation of dendritic cells resulting
in effective peptide antigen presentation. . . . This this leads to
T and B cell clonal expansion, creating immunity in the patient.
The resulting infiltration into tumors by hematogenous spread
leads to robust tumor destruction. The result... is increased
survival due to immunologic memory. . . . [D]endritic cell
activation and maturation are considered key factors in cancer
immunodeficiency as well as the well-known defects in T cells
such as a decreased number and function with anergy and
presumed apoptosis.
(Spec. 8—9 (citations omitted); cf. Hadden ’983 1: 5—6, 1: 8—11, 1: 27—31, 3:
20-21, 4: 3—8, 14: 4—10, and 16: 39-52; see generally Ans. 2—3.)
FF 4. Appellant “predicts] logically that exogenously provided synthetic
or extracted tumor peptides . . . can be delivered into the pre-primed or co­
primed regional or distal lymph node and yield tumor antigen specific T
cells, with or without B cells” (Spec. 9; see Ans. 3 (“it would have been
obvious to administer the NCM cytokine along with the antigen in the same
composition, or on the same day, as a matter of convenience. Furthermore,
the ordinary artisan would have a reasonable expectation of success,”
because Eisenbach “teaches that the tumor antigen peptides are suitable for
use in conjunction with many of the same cytokines in the NCM
administered in the method of [Hadden ’983]”).
FF 5. Appellant discloses a
method of enhancing the immune response of cancer patients to
a cancer by administering an effective amount of a composition
containing therein [a natural cytokine mixture (NCM)] plus
thymosin al and a tumor associated antigen, the NCM plus
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thymosin al acting as an adjuvant to produce the immune
response.
(Spec. 9; cf Hadden ’983 1: 5-6, 1: 8-11, 1: 27-31, 3: 20-21, 4: 3-8, 14: 4—
10, and 16: 39-52.)
FF 6. Appellant defines the term “adjuvant” as “a composition with the
ability to enhance the immune response to a particular antigen. To be
effective, an adjuvant must be delivered at or near the site of antigen. Such
ability is manifested by a significant increase in immune mediated
protection” (Spec. 10; cf Hadden ’983 6: 38-49 (disclosing that the
combination of NCM and Thymosin al “can be administered in various
ways,” including “[sjite specific administration i.e., regional to a cancer is
preferred if possible so that adjuvant effects are realized”); see also Hadden
’983 8: 14—15; Ans. 2—3).
FF 7. Appellant defines the term “NCM” as “a non-recombinant cytokine
mixture ... as set forth in[, inter alia,] Hadden ’983” (Spec. 10; see
generally Hadden ’983 1: 38-45, 7: 5—19, and 16: 39-52).
FF 8. Appellant discloses that
[ujpon administration of [the] NCM to immunosuppressed
patients with head and neck cancer, it is demonstrated in this
application for the first time that the mobilization of T
lymphocytes in the blood of cancer patients treated with the
NCM produces an increase in immature, naive T cells bearing
both CD2 and CD45 RA.
(Spec. 14 (emphasis added); cf Co-pending Application 13/940,558,
September 20, 2013 Substitute Specification, 11; Hadden ’983 6: 36—37 (an
“[ejxample of the clinical use [of NCM] is exemplified by [Hadden ’94(a)]);
see Hadden ’983 15: 24—26.)
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FF 9. Appellant defines the term “pharmaceutically ‘effective amount’” as
“determined by such considerations as are known in the art,” wherein “[t]he
amount must be effective to achieve immunization, including but not limited
to, tumor reduction, fragmentation and infiltration, survival rate or more
rapid recover, or improvement or elimination of symptoms” (Spec. 17; cf
Hadden ’983 6: 27—37 (disclosing that the term “effective amount,” as used
in Hadden ’983’s disclosure,
is thus determined by such considerations as are known in the
art. The amount must be effective to show improvement in
immune function in 25% of patients treated including, but not
limited to, improved responses in vitro measurements of
cellular immune function, increased T lymphocyte levels in
vivo, improved skin test response to recall antigens or NCM,
improved survival rate, more rapid recovery, or improvement or
elimination of symptoms and in cancer reduction of tumor
mass.
{See also Hadden ’983 5: 60—67; see generally Ans. 2—3.))
FF 10. Hadden ’983 discloses that “NCM may be used with other
treatments to improve immune function and treat cancer” (Hadden ’983 6:
34—36; see Ans. 7 (citing Hadden ’983 6 and 8) (Hadden ’983 discloses “that
the NCM is administered in an amount sufficient to increase T cells and
improve T lymphocyte responses to antigens (i.e. induce an immune
response in the subject)”).
FF 11. Hadden ’983 discloses that “IL-2,” inter alia, “induces and supports
proliferation of antigen or mitogen stimulated T-cells” (Hadden ’983 1: 47—
49).
FF 12. Hadden ’983 does not disclose administering an exogenous antigen
together with a composition comprising a combination of NCM and
thymosin al (Ans. 3 and 5).
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FF 13. Eisenbach “relates to tumor associated antigen (TAA) peptides and
to the use of same, of polynucleotides encoding same and of cells presenting
same as anti-tumor vaccines” (Eisenbach 1: 5—7; see id. at 8: 4—7 (Eisenbach
“provides] novel tumor associated antigen peptides effective in eliciting
CTL response which may [] be effective therapeutic agents to combat
cancer”); id. at 23: 1—3; Ans. 3 (Eisenach discloses “administration of
exogenous tumor antigen peptides to treat subjects with cancer”)).
Eisenbach discloses that “the phrase ‘anti-tumor vaccines’ refers to vaccines
effective in preventing the development of, or curing, cancer, including
primary tumor and/or metasteses” (Eisenbach 20: 36—38; see Ans. 3).
FF 14. Eisenbach discloses the use of a peptide derived from, inter alia,
“Prostate specific membrane antigen (PSMA)” (Eisenbach 4: 13—15; see
also Ans. 3).
FF 15. Eisenbach discloses that “the tumor associated antigen peptide[s] are
presented in [the] context of [a] carrier,” which includes an adjuvant and
“cytokines, such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-
10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, interferon alpha,
interferon beta, interferon gamma and others” (Eisenbach 21: 14—26; see
Ans. 3).
FF 16. Examiner finds that the combination of Hadden ’983 and Eisenbach
fail to disclose the administration of “cyclophosphamide, a nonsteroidal anti­
inflammatory drug (NSID), or zinc” (Ans. 4).
FF 17. Hadden ’94(a) discloses the treatment of
[mjetastatic squamous cell head and neck cancer . . . with low-
dose cyclophosphamide (to reduce suppressor T-cell activity),
indomethacin (to reduce prostaglandins that mediate
macrophage-induced immune suppression), zinc (to augment T-
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cell function via thymulin), and mixed natural interleukins
perilymphatically in the neck (as adjuvant for tumor antigen in
the region).
(Hadden ’94(a), Abstract; see Ans. 4.)
FF 18. Examiner finds that Hadden ’99 discloses “NCM . . . vaccine therapy
comprising administration of exogenous tumor antigens” and “that
combined use of therapies including vaccines, interleukins,
cyclophosphamide, and indomethacin have complementary
immunopharmacologies and should be compatible” (Ans. 5 (citing Hadden
’99 92); see also Hadden ’99, Abstract).
FF 19. Examiner finds that Hadden ’99 discloses “that zinc can [] be used in
combination with indomethacin and cyclophosphamide for treating cancer”
(Ans. 5 (citing Hadden ’99 90)).
FF 20. Examiner finds that Hadden ’94(b) discloses “that interleukins and
thymic hormones act to promote TH cell responses and that coupling such
agents with antigens is useful in efforts to produce T cell adjuvenicity” (Ans.
6 (citing Hadden ’94(b) 707)).
ANALYSIS
The rejection over the combination of Hadden ’983 and Eisenbach:
Appellant recognized that it was known in the art, prior to the filing
date of Appellant’s claimed invention, that a “fundamental problem in the
effort to immunize cancer patients is that the tumor-bearing state is
associated with immunosuppressive mechanisms derived from both the
tumor and the host’s disturbed immune system” that makes “immunization
difficult” (FF 1). Thus, Appellant sought to overcome, or unblock, this
immunosuppression and, thereby, restore immunological function so that an
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immune response to at least one exogenous tumor antigen can be stimulated
by administering, to the cancer patient, an effective amount of NCM
together with a thymic peptide, such as thymosin al, and at least one
exogenous antigen, on the same day, so as to induce an immune response in
the patient (see FF 1—9; see also Appellant’s claim 33).
Methods of inducing an immune response in a patient comprising
administering an exogenous antigen and an adjuvant were not new to
Appellant’s disclosure. To the contrary, such methods were well known in
this art at the time of Appellant’s claimed invention (see FF 13—15).
The use of a cytokine or cytokine mixture, as an adjuvant, in a method
of inducing an immune response to an exogenous antigen was also not new
to Appellant’s disclosure, but was instead routine in this art prior to the
filing date of Appellant’s claimed invention (see FF 15 (Eisenbach discloses
administering “tumor associated antigen peptide[s]... in [the] context of [a]
carrier,” which includes an adjuvant and/or cytokines)); FF 2 (“A major
class of immunomodulators is cytokines”); FF 6 (Hadden ’983 discloses a
preferred site for NCM administration to realize NCM’s “adjuvant effects”).
Thus, while Eisenbach does not expressly disclose that cytokines are
adjuvants, we find that identical language between the prior art and claims is
not required to sustain a prior-art rejection. In re Skoner, 517 F.2d 947, 950
(CCPA 1975) (“Any other result would permit the allowance of claims
drawn to unpatentable subject matter merely through the employment of
descriptive language not chosen by the prior art”). In addition, we note that
Appellant’s claim 33 does not require the NCM and/or thymosin peptide to
directly induce an immune response to an exogenous antigen in a subject
(see Appellant’s claim 33). Nevertheless, given that Hadden ’983 discloses
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that a cytokine mixture, NCM, which may be administered in conjunction
with a thymosin peptide, exhibits adjuvant activity and an ability to improve
a cellular immune response in a patient, we find no error in Examiner’s
conclusion that it would have been prima facie obvious to use the NCM
disclosed by Hadden ’983 in Eisenbach’s method or, in the alternative, to
add an exogenous antigen to the method disclosed by Hadden ’983 (see Ans.
3; see also id. at 11—12; FF 1—10). Therefore, we are not persuaded by
Appellant’s contention that Eisenbach “does not provide any data showing
that a single cytokine, let alone a mixture of cytokines, enhances an antigen-
specific T cell response to an exogenous antigen,” which fails to account for
Hadden ’983’s contribution to the combination of Hadden ’983 and
Eisenbach (App. Br. 11). See In re Merck & Co., 800 F.2d 1091, 1097 (Fed.
Cir. 1986) (Each reference “must be read, not in isolation, but for what it
fairly teaches in combination with the prior art as a whole”). In addition, we
note that the method of Appellant’s claim 33 does not require NCM or a
thymosin peptide, alone or in combination, to directly induce an immune
response to an exogenous antigen in a subject (see App. Br. 30). In this
regard, Eisenbach makes clear that the administration of an exogenous
antigen to a patient will induce an immune response to the exogenous
antigen (see FF 13—15).
Hadden ’983 recognized the “limited efficacy” of prior cytokine
therapies, potential “toxicity” associated with the use of cytokines, and the
number of potential cytokine combinations (see FF 1). Hadden ’983,
therefore, set out to overcome these prior art hurdles in the use of cytokine
mixtures as, inter alia, adjuvants, in a method of improving cellular immune
response in a patient and successfully developed a specific mixture of
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cytokines, NCM, that may be combined with thymosin al and overcomes
the prior art problems with cytokine therapy, overcomes the
immunosuppressive state of cancer patients, exhibits adjuvant effects, and
improves cellular immune response in a patient (see FF 1—3 and 5—9). There
is no dispute on this record that Hadden ’983 ’s NCM is the natural cytokine
mixture and is prepared by the same process and that Hadden ’983 discloses
the combination of NCM with thymosin al as is required by Appellant’s
claim 33 (see FF 6—7).
Although Hadden ’983 discloses an effective mixture of cytokines for
use in, inter alia, the treatment of cancer, Hadden ’983 does not disclose a
vaccine composition that comprises NCM and an exogenous antigen (FF 1—
12). Hadden ’983, however, discloses that its “treatment methods can be
performed [in combination] with other cancer treatment regimens” such as
those disclosed by Eisenbach, which includes administration of an
exogenous antigen, such as the PSMA tumor associated antigen in a carrier
that comprises cytokines, such as those disclosed by Hadden ’983 (see FF 1—
15). There is no dispute on this record that the prior art suggests amounts of
antigen, thymosin al, and NCM that are effective for administration to a
subject to stimulate an immune response to the antigen as is required by
Appellant’s claim 33 or that such amounts could not have been “determined
by such considerations as are known in the art” (see e.g., FF 9; see generally
1-15). In re Geisler, 116 F.3d 1465, 1470, (Fed. Cir. 1997) (“‘[I]t is not
inventive to discover the optimum or workable ranges by routine
experimentation.’”) (quoting In re Aller, 220 F.2d 454, 456 (CCPA 1955)).
Therefore, we are not persuaded by Appellant’s contention that Hadden ’983
fails to suggest “eliciting an antigen-specific immune response to an
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exogenous antigen by administering the exogenous antigen in combination
with a cytokine mixture and a thymic peptide,” which fails to account for
Eisenbach’s contribution to the combination of Hadden ’983 and Eisenbach
(see App. Br. 10; cf. FF 1—15). See In re Merck & Co., 800 F.2d at 1097.
Therefore, as discussed above, we find no error in Examiner’s
conclusion that, at the time of Appellant’s claimed invention, a person of
ordinary skill in this art would have found it prima facie obvious,
to use the NCM disclosed by Hadden ’983 in Eisenbach’s method or, in the
alternative, to add an exogenous antigen to the method disclosed by Hadden
’983 (see Ans. 3; see also id. at 11—12; FF 1—15). Although a person of
ordinary skill in this art would have reasonably and logically expected that a
restored immune system would have facilitated a response to an exogenous
antigen,18 Hadden ’983 provides a reason to combine its composition
comprising NCM and thymosin al with other cancer treatment regimens,
which include the administration of an exogenous tumor associated antigen,
such as PSMA, in combination with cytokines as disclosed by Eisenbach, to
elicit a response to the exogenously supplied tumor associated antigen (see
FF 1—15; see also Ans. 12 (Hadden ’983 and Eisenbach “both [] teach that
the compositions (either the NCM or the peptide antigen) are effective for
the same purpose, i.e. improving the immune response to treat cancer”)).
Thus, on this record, Hadden ’983 suggests its combination with Eisenbach
and Eisenbach suggests its combination with Hadden ’983. Therefore, we
are not persuaded by Appellant’s contention that “[hjaving a ‘restored’
18 See In re O’Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988)
(“Obviousness does not require absolute predictability of success ... all that
is required is a reasonable expectation of success”).
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immune system[, as disclosed by Hadden ’983] is not predictive of whether
a subject will respond to an exogenous antigen” (App. Br. 10; cf. FF 1—15).
To the contrary, the evidence relied upon by Examiner supports a conclusion
that a person of ordinary skill in this art would have combined Hadden
’983’s NCM with Eisenbach’s exogenous antigen in order to induce an
immune response to the exogenous antigen in a subject, with a reasonable
expectation of success (see FF 1—10).
In sum, the combination of Hadden ’983 and Eisenbach suggest the
combination of familiar elements according to known methods to yield a
predictable result. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416
(2007) (“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results”).
In this regard, we note that “[ojbviousness does not require absolute
predictability of success ... all that is required is a reasonable expectation of
success.” See In re O'Farrell, 853 F.2d at 903—904; cf. Naylor19110 (“the
literature at the time [of Appellant’s claimed invention] and . . . [Eisenbach]
does not provide certainty” and “Cavallion20 specifically calls into question
the concept of pro- and anti-inflammatory cytokines and teaches that it is not
possible to predict with certainty how any individual cytokine or
combination of cytokines will act when administered in vivo both with
respect to immune activation or suppression”) (emphasis added).
Notwithstanding Naylor’s statements to the contrary, “certainty” is not
19 Declaration of Paul H. Naylor, Ph.D., signed July 5, 2014.
20 Jean-Marc Cavaillon, Pro-versus Anti-Inflammatory Cytokines: Myth or
Reality, 47 Cellular and Molecular Biology 695—702 (2001).
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required to achieve a reasonable expectation of success. To the contrary,
where, as here,
a person of ordinary skill can implement a predictable variation,
§ 103 likely bars its patentability. For the same reason, 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.
KSR, 550 U.S. at 417. On this record, Appellant failed to provide persuasive
argument or evidence to support a conclusion that by performing the method
suggested by the combination of Hadden ’983 and Eisenbach, an antigen-
specific response to an exogenous antigen would not have been induced as
required by Appellant’s claim 33 (cf. App. Br. 11). Therefore, we are also
not persuaded by Appellant’s contention that:
Examiner has not established a prima facie case because she
has not met her burden in establishing that one of ordinary skill
in the art would have had a reasonable expectation of success
based on the cited art of inducing an immune response to an
exogenous antigen upon administering NCM, a thymic peptide,
and the exogenous antigen to a subject.
(App. Br. 12 (citing Naylor).)
As discussed above, there is no dispute on this record that Hadden
’983’s NCM is the same natural cytokine mixture as is required by
Appellant’s claim 33. Appellant appears to be the inventor of the subject
matter of Hadden ’983. Appellant and Hadden ’983 both disclose similar
features and/or benefits associated with NCM (see FF 1—10). Nevertheless,
Appellant contends that “the mechanism of action of the NCM was not
known at the time of the filing [of] the present application, and any
statements in the art at the time of the filing of the instant application
regarding the mechanism of action were ‘inferential and speculative’” (App.
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Br. 16 (citing Naylor 112). Stated differently, subsequent to Appellant’s
earlier Hadden ’983 Patent, Appellant discovered new properties and/or
benefits associated with the combination of NCM and a thymosin peptide
with other cancer therapies. Hadden ’983, however, discloses a composition
comprising NCM, together with thymosin al, for use in combination with
other cancer therapies that were known in the art, such as those disclosed by
Eisenbach (see FF 1—15). Thus, Hadden ’983 disclosed, what was at the
time of Appellant’s filing date, an old process. See King Pharmaceuticals,
Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1275—76 (Fed. Cir. 2010) (“[Mjerely
discovering and claiming a new benefit of an old process cannot render the
process again patentable.”); In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir.
1990). Therefore, we are not persuaded by Appellant’s contention that the
observation and further characterization of a composition comprising NCM
and thymosin al alone or in combination with other therapies, as disclosed
by Hadden ’983, renders Appellant’s old method newly patentable.
Further, we recognize Appellant’s contentions and Naylor’s
statements regarding NCM’s mechanism of action and citation to a number
of supplemental documents, which allegedly support a conclusion that
cytokines exhibit different activities (see App. Br. 12—18; Naylor || 8—15).
Hadden ’983, however, recognized these concerns in the art and set out to
overcome these prior art hurdles in the use of cytokine mixtures as adjuvants
and successfully developed a specific mixture of cytokines, NCM, that can
be combined with thymosin al, which overcomes the prior art problems
with cytokine therapy, overcomes the immunosuppressive state of cancer
patients, exhibits adjuvant effects, and facilitates an immune response (see
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FF 1—10). There is no dispute on this record that Hadden ’983 ’s NCM is the
natural cytokine mixture required by Appellant’s claim 33 (see FF 7).
As this record makes clear, Hadden ’983’s disclosure of an effective
cytokine mixture in combination with thymosin al ‘“puts the key in the lock
of the door of success’. All that remains for a person having ordinary skill is
to turn the key and, in so doing, open the lock. That, in our judgment, does
not give rise to a patentable invention.” See Ex parte Goldgaber, 41
USPQ2d 1172, 1175 (Bd. Pat. App. & Int. 1995). Therefore, we are not
persuaded by Appellant’s contentions and Naylor’s statements regarding the
complexity of the cytokine network or the prior art’s concerns relating to
cytokines, which were recognized and overcome by Hadden ’983 (see App.
Br. 12-18; Naylor H 8-15; cf. FF 1-15).
For the foregoing reasons, we are not persuaded by Naylor or
Appellant’s reliance thereon (see Naylor || 8—15; App. Br. 12—18). As
discussed above, we are not persuaded by Appellant’s contention and
Naylor’s statement that “[wjithout the knowledge of the mechanism of
action of NCM, one of ordinary skill in the art would not have predicted that
an antigen specific response to an exogenous antigen would be the result of
administering the antigen with a NCM and a thymic peptide” (App. Br. 17
(citing Naylor 112); see generally id. at 12—18). Notwithstanding
Appellant’s contention to the contrary, Hadden ’983 discloses the same
NCM required by Appellant’s claim 33, in combination with a thymic
peptide and its use as an adjuvant in combination with other cancer
therapies, such as those disclosed by the combination of Eisenbach (FF 1—
15). The observation and further understanding of a composition comprising
NCM and thymosin al and its mechanism of action, which are properties of
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the composition itself, does not support a conclusion of non-obviousness on
this record. See In re Papesch, 315 315 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”). Further, on this record,
Appellant failed to provide persuasive evidence or argument to support a
conclusion that the administration of an exogenous antigen together with
NCM and thymosin al, as suggested by the combination of Hadden ’983
and Eisenbach, to a patient in need thereof would not have achieved the
same result as obtained by performing the method of Appellant’s claim 33
(see FF 1-15).
For the foregoing reasons, we are not persuaded by Appellant’s
contention that Naylor “provides sufficient factual evidence to rebut the
Examiner’s allegation that a person of ordinary skill in the art would have
had a reasonable expectation of success based on the cited art” (App. Br.
12). For the same reasons, we are not persuaded by Appellant’s contention
that “Examiner has not taken into account all of the art and evidence of
record and has made an erroneous rejection of the claims” (Reply Br. 4).
The rejection over the combination of Hadden ’983, Eisenbach, and Hadden
’94(a):
Based on the combination of Hadden ’983, Eisenbach, and Hadden
’94(a), Examiner concludes that, at the time Appellant’s invention was
made, it would have been prima facie obvious to “administer
cyclophosphamide, indomethacin, and zinc, as taught by [Hadden ’94(a)], in
the method of treating cancer, as taught by the [combination of Hadden ’983
and Eisenbach]” (Ans. 4). We find no error in Examiner’s prima facie case
of obviousness (see FF 1—17).
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We are not persuaded by Appellant’s contention that Hadden ’94(a)
“does not each or suggest that administering a NCM, a thymic peptide, and
an exogenous antigen would result in an immune response to an exogenous
antigen in a subject,” which, as discussed above, is suggested by the
combination of Hadden ’983 and Eisenbach (App. Br. 18).
The rejection over the combination of Hadden ’983, Hadden ’99, and
Hadden ’94(b):
Based on the combination of Hadden ’983, Hadden ’99, and Hadden
’94(b), Examiner concludes that, at the time Appellant’s invention was
made, it would have been prima facie obvious to “administer a tumor
antigen and indomethacin and cyclophosphamide, as taught by [Hadden
’99], in the method of treating a cancer, as taught by the [combination of
Hadden ’983 and Hadden ’94(b)]” (Ans. 6; see also id. at 16—17). We find
no error in Examiner’s prima facie case of obviousness (see FF 1—12 and
18-20).
Hadden ’983 discloses the administering a composition comprising
NCM and thymosin al to patients in an amount “effective to show
improvement in immune function . . . including, but not limited to, . . .
cancer reduction of tumor mass” (FF 9; see also FF 1—8 and 10—12). In this
regard, Hadden ’983 discloses that its “treatment methods can be performed
[in combination] with other cancer treatment regimens” such as those
disclosed by Hadden ’99, which includes administration of a NCM vaccine
comprising exogenous tumor antigens (see FF 18; see also FF 1—12).
Therefore, we are not persuaded by Appellant’s contention that the
combination of Hadden ’983, Hadden ’99, and Hadden ’94(b) “would not
have led one of ordinary skill in the art to have a reasonable expectation of
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success that the claimed administration of NCM, a thymic peptide, and an
exogenous antigen would stimulate an immune response to the exogenous
antigen” (see App. Br. 20; cf. FF 1—12 and 18—20).
For the foregoing reasons, we are not persuaded by Appellant’s
reliance on their arguments above, and the Naylor Decl., regarding a
mechanism of action (App. Br. 20).
CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness.
The rejection of claim 33 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Hadden ’983 and Eisenbach is affirmed. Claims
34—38 and 46—50 are not separately argued and fall with claim 33.
The rejection of claim 40 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Hadden ’983, Eisenbach, and Hadden ’94(a) is
affirmed. Claims 41—45 are not separately argued and fall with claim 40.
The rejection of claim 33 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Hadden ’983, Hadden ’99, and Hadden ’94(b) is
affirmed. Claims 34—38, 40-48, and 50 are not separately argued and fall
with claim 33.
Obviousness-type Double Patenting'.
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness-type double patenting?
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FACTUAL FINDINGS (FF)
FF 21. Hadden ’072’s claim 1 is reproduced below:
1. A method for unblocking immunization at a regional lymph
node of a patient comprising:
(i) perilymphatically administering a natural cytokine mixture
[(NCM)] to a patient having an accumulation of dendritic
cells, which have ingested or processed an antigen but are
unable to mature, whereby said perilymphatic administration
promotes the differentiation and maturation of the said
dendritic cells; and
(ii) administering to the patient cyclophosamide and an NS AID,
whereby said administration decreases T-cell suppression.
(Hadden ’072 24: 26—37 (emphasis added).)
FF 22. Hadden ’072’s claim 6 defines the antigen of Hadden ’072’s claim 1
as “an exogenous antigen” (Hadden ’072 24: 48-49).
FF 23. Hadden ’072’s claim 2 depends from and further defines step (i) of
Hadden ’072’s claim 1 “as administering a . . . [NCM] perilymphatically
into lymphatics that drain into lymph nodes regional to a lesion to be
treated” (Hadden ’072 24: 38^11).
FF 24. Hadden ’072’s claim 7 defines the NCM of Hadden ’072’s claim 1
as “including IL-1, IL-2, IL-6, IL-8, 8IFN and TNFa” (Hadden ’072’s 24:
50-52).
FF 25. Hadden ’517’s claim 1 is reproduced below:
1. A method of immunotherapy to treat cancer in a patient
comprising:
administering an effective amount of a cytokine mixture
comprising IL-1, IL-2, IL-6, IL-8, IFN-y, and TNF-a to the
patient; and
administering an effective amount of at least one exogenous
tumor peptide antigen to the patient,
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wherein the cytokine mixture acts as an adjuvant and stimulates
in the patient an enhanced antigen-specific immune response
to the at least one exogenous tumor peptide antigen.
(Hadden ’517 42: 33—43.)
FF 26. Hadden ’517’s claim 7 defines the cytokine mixture of Hadden
’517’s claim 1 as a “natural cytokine” mixture (NCM) (Hadden ’517 42: 59-
60).
FF 27. Hadden ’517’s claim 5 ultimately depends from and further limits
Hadden ’517’s claim 1 to require that the “cytokine mixture and the at least
one exogenous tumor peptide antigen are administered at the same time”
(Hadden ’517 42: 53-55).
FF 28. Hadden ’779’s claim 30 is reproduced below:
30. A method for inducing an immune response to at least one
exogenous antigen in a patient, the method comprising:
administering to the patient an effective amount of a natural
cytokine mixture [(NCM)] comprising the cytokines IL-1
beta, IL-2, IL-6, IL-8, IFN-gamma, and TNF-alpha; and
administering to the patient an effective amount of at least one
exogenous antigen,
wherein the . . . [NCM] acts as an adjuvant with the at least one
exogenous antigen and stimulates an immune response to the
at least one exogenous antigen in the patient.
(Hadden ’779 13: claim 30.)
FF 29. Hadden ’779’s claim 35 depends from and further defines the NCM
of Hadden ’779’s claim 30 to “further comprise^ GM-CSF and G-CSF”
(Hadden ’779 14: claim 35).
FF 30. Hadden ’796’s claim 1 is reproduced below:
1. A method for treating hepatocellular cancer in a patient, the
method comprising: administering to the patient having
hepatocellular cancer an effective amount of a natural
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cytokine mixture [(NCM)] comprising the cytokines IL-
lbeta, IL-2, IL-6, IL-8, IFN-gamma, and TNF-alpha.
(Hadden ’796 24: 58-62.)
FF 31. Hadden ’796’s claim 6 depends from and further defines the NCM of
Hadden ’796’s claim 1 to further comprise GM-CSF and G-CSF (Hadden
’796 25: 13-14).
FF 32. Hadden ’796’s claim 5 depends from and further limits Hadden
’796’s claim 1 to “further comprises: administering to the patient an
effective amount of at least one exogenous tumor antigen” (Hadden ’796 25:
9-12).
FF 33. Hadden ’519’s claim 1 is reproduced below:
1. A method for treating a patient having advanced prostate
cancer, the method comprises:
(a) administering to the patient having advanced prostate cancer
an effective amount of a composition comprising a natural
cytokine mixture (NCM), the NCM comprising IL-1, IL-2,
IL-6, IL-8, IFN-gamma, and TNF-alpha; and
(b) administering to the patient an effective amount of at least
one exogenous tumor antigen,
wherein the cytokines act as an adjuvant with the at least one
exogenous tumor antigen and stimulate an immune response
to the at least one exogenous tumor antigen in the patient;
wherein the immune response is effective to alleviate or
eliminate symptoms and effects of the advanced prostate
cancer in the patient;
wherein the patient has previously received surgery,
radiotherapy, chemotherapy, or combinations thereof; and
wherein after surgery, radiotherapy, chemotherapy, or
combinations thereof the patient has tumor recurrence, a rise
in PSA antigen levels, or a combination thereof.
(Hadden’519 43: 59-44: 13.)
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FF 34. Hadden ’519’s claim 2 depends from and further limits Hadden
’519’s claim 1 to comprise “administering the composition and the at least
one exogenous tumor antigen at the same time” (Hadden ’519 44: 13—15).
ANALYSIS
The rejection over the claims of Hadden ’072 in view of Hadden ’983,
Hadden ’94(a), andEisenbach:
Based on the combination of Hadden ’072 in view of Hadden ’983,
Hadden ’94(a), and Eisenbach, Examiner concludes that, at the time
Appellant’s invention was made, it would have been prima facie obvious to
substitute Hadden ’072’s NCM composition with a composition comprising
thymosin-al and NCM, which falls within the scope of the NCM of
Appellant’s claim 33, for the benefits suggested by Hadden ’983 (Ans. 7 and
17 ; see FF 21—24 and 1—12; see also FF 13—15 (Eisenbach discloses the
administration of an exogenous antigen together with a carrier comprising
cytokines)). In addition, Examiner reasons that “it would [have been]
obvious to administer the various treatments on the same day as a matter of
convenience” (Ans. 8). We find no error in Examiner’s prima facie case.
Appellant contends that Examiner failed to “establish[] that one of
ordinary skill in the art would have had a reasonable expectation of success
based on the cited art of inducing an immune response to an exogenous
antigen upon administering NCM, a thymic peptide, and the exogenous
antigen to a subject” (App. Br. 21; see also id. at 21—22 (citing Naylor
Deck)). We are not persuaded.
Eisenbach suggests the administration of a composition comprising an
exogenous antigen and cytokines to induce an immune response to the
exogenous antigen in a subject (see FF 13—15). Hadden ’072’s claimed
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method comprises the administration of NCM and an exogenous antigen to
decrease T-cell suppression, and, thereby, enhance the immune response (FF
21—24). Hadden ’983 discloses the administration of a composition
comprising NCM and thymosin-al to, inter alia, “increase^ T lymphocyte
levels in vivo, . . . improved survival rate, [provide] more rapid recovery, or
improvement or elimination of symptoms and in cancer reduction of tumor
mass” and further discloses that the composition “may be used with other
treatments to improve immune function and treat cancer” (FF 9; cf Spec. 17:
19—23). Thus, notwithstanding Appellant’s contention to the contrary, when
taken as a whole, Hadden ’072 in combination with Hadden ’983, Hadden
’94(a), and Eisenbach provides a person of ordinary skill in this art with a
reasonable expectation of success in inducing an immune response to an
exogenous antigen in a subject. See In re O'Farrell, 853 F.2d at 903-904
(Fed. Cir. 1988) (“Obviousness does not require absolute predictability of
success ... all that is required is a reasonable expectation of success”).
The rejection over the claims of Hadden ’517 in view of Hadden ’983 and
Eisenbach'.
Based on the combination of Hadden ’517 in view of Hadden ’983
and Eisenbach, Examiner concludes that, at the time Appellant’s invention
was made, it would have been prima facie obvious to substitute Hadden
’517’s NCM composition with a composition comprising thymosin-al and
NCM, which falls within the scope of the NCM of Appellant’s claim 33, for
the benefits suggested by Hadden ’983 (Ans. 8 and 17; see FF 25—27 and 1—
12; see also FF 12—15 (Eisenbach discloses the administration of an
exogenous antigen together with a carrier comprising cytokines)). In
addition, Examiner reasons that “it would [have been] obvious to administer
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the various treatments on the same day as a matter of convenience” (Ans. 8;
see FF 27). We find no error in Examiner’s prima facie case.
Appellant contends that Examiner failed to “establish[] that one of
ordinary skill in the art would have had a reasonable expectation of success
based on the cited art of inducing an immune response to an exogenous
antigen upon administering NCM, a thymic peptide, and the exogenous
antigen to a subject” (App. Br. 22—23 (citing Naylor Decl.)). We are not
persuaded.
Eisenbach suggests the administration of a composition comprising an
exogenous antigen and cytokines to induce an immune response to the
exogenous antigen in a subject (see FF 12—15). Hadden ’517 claims a
method of immunotherapy, “wherein . . . [NCM] acts as an adjuvant and
stimulates in the patient an enhanced antigen-specific immune response to []
at least one exogenous tumor peptide antigen” (FF 25; see also id. FF 26—
27). Hadden ’983 discloses the administration of a composition comprising
NCM and thymosin-al to, inter alia, “increase^ T lymphocyte levels in
vivo, . . . improved survival rate, [provide] more rapid recovery, or
improvement or elimination of symptoms and in cancer reduction of tumor
mass” and further discloses that the composition “may be used with other
treatments to improve immune function and treat cancer” (FF 9; cf Spec. 17:
19—23). Thus, notwithstanding Appellant’s contention to the contrary, when
taken as a whole, Hadden ’517 in combination with Hadden ’983 and
Eisenbach provides a person of ordinary skill in this art with a reasonable
expectation of success in inducing an immune response to an exogenous
antigen in a subject. See In re O'Farrell, 853 F.2d at 903-904 (Fed. Cir.
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1988) (“Obviousness does not require absolute predictability of success . . .
all that is required is a reasonable expectation of success”).
The provisional rejection over the claims of Hadden ’779 in view of Hadden
’983 and Hadden ’94(a):
Based on the combination of Hadden ’779 in view of Hadden ’983
and Hadden ’94(a), Examiner concludes that, at the time Appellant’s
invention was made, it would have been prima facie obvious to substitute
Hadden ’779’s NCM composition with a composition comprising thymosin-
al and NCM, which falls within the scope of the NCM of Appellant’s claim
33, for the benefits suggested by Hadden ’983 (Ans. 9 and 18; see FF 28—29
and 1—12). In addition, Examiner reasons that “it would [have been]
obvious to administer the various treatments on the same day as a matter of
convenience” (Ans. 9). We find no error in Examiner’s prima facie case.
Appellant contends that Examiner failed to “establish[] that one of
ordinary skill in the art would have had a reasonable expectation of success
based on the cited art of inducing an immune response to an exogenous
antigen upon administering NCM, a thymic peptide, and the exogenous
antigen to a subject” (App. Br. 24 (citing Naylor Decl.)). We are not
persuaded.
Hadden ’779’s claimed method comprises the administration of NCM
and at least one exogenous antigen to induce an immune response to the at
least one exogenous antigen (FF 28—29). Hadden ’983 discloses the
administration of a composition comprising NCM and thymosin-al to, inter
alia, “increase^ T lymphocyte levels in vivo, . . . improved survival rate,
[provide] more rapid recovery, or improvement or elimination of symptoms
and in cancer reduction of tumor mass” and further discloses that the
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composition “may be used with other treatments to improve immune
function and treat cancer” (FF 9; cf Spec. 17: 19-23). Thus,
notwithstanding Appellant’s contention to the contrary, when taken as a
whole, Hadden ’779 in combination with Hadden ’983 and Hadden ’94(a)
provides a person of ordinary skill in this art with a reasonable expectation
of success in inducing an immune response to an exogenous antigen in a
subject. See In re O'Farrell, 853 F.2d at 903-904 (Fed. Cir. 1988)
(“Obviousness does not require absolute predictability of success ... all that
is required is a reasonable expectation of success”).
The rejection over the claims of Hadden ’796 in view of Hadden ’983,
Hadden ’94(a), andEisenbach:
Based on the combination of Hadden ’796 in view of Hadden ’983,
Hadden ’94(a), and Eisenbach, Examiner concludes that, at the time
Appellant’s invention was made, it would have been prima facie obvious to
substitute Hadden ’796’s NCM composition with a composition comprising
thymosin-al and NCM, which falls within the scope of the NCM of
Appellant’s claim 33, for the benefits suggested by Hadden ’983 (Ans. 9—10
and 18 ; see FF 30—32 and 1—12; see also FF 12—15 (Eisenbach discloses the
administration of an exogenous antigen together with a carrier comprising
cytokines)). In addition, Examiner reasons that “it would [have been]
obvious to administer the various treatments on the same day as a matter of
convenience” (Ans. 10). We find no error in Examiner’s prima facie case.
Appellant contends that Examiner failed to “establish[] that one of
ordinary skill in the art would have had a reasonable expectation of success
based on the cited art of inducing an immune response to an exogenous
antigen upon administering NCM, a thymic peptide, and the exogenous
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antigen to a subject” (App. Br. 25 (citing Naylor Decl.)). We are not
persuaded.
Eisenbach suggests the administration of a composition comprising an
exogenous antigen and cytokines to induce an immune response to the
exogenous antigen in a subject (see FF 12—15). Hadden ’796’s claimed
method comprises the administration of NCM and an exogenous antigen to
treat hepatocellular cancer in a patient (FF 30-32). Appellant offers no
persuasive evidence or argument to support a conclusion that Hadden ’976’s
method does not result in inducing an immune response to the exogenous
antigen. Hadden ’983 discloses the administration of a composition
comprising NCM and thymosin-al to, inter alia, “increase^ T lymphocyte
levels in vivo, . . . improved survival rate, [provide] more rapid recovery, or
improvement or elimination of symptoms and in cancer reduction of tumor
mass” and further discloses that the composition “may be used with other
treatments to improve immune function and treat cancer” (FF 9; cf Spec. 17:
19—23). Thus, notwithstanding Appellant’s contention to the contrary, when
taken as a whole, Hadden ’796 in combination with Hadden ’983, Hadden
’94(a), and Eisenbach provides a person of ordinary skill in this art with a
reasonable expectation of success in inducing an immune response to an
exogenous antigen in a subject. See In re O'Farrell, 853 F.2d at 903-904
(Fed. Cir. 1988) (“Obviousness does not require absolute predictability of
success ... all that is required is a reasonable expectation of success”).
The rejection over the claims of Hadden ’519 in view of Hadden ’983:
Based on the combination of Hadden ’519 in view of Hadden ’983,
Examiner concludes that, at the time Appellant’s invention was made, it
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would have been prima facie obvious to substitute Hadden ’519’s NCM
composition with a composition comprising thymosin-al and NCM, which
falls within the scope of the NCM of Appellants’ claim 33, for the benefits
suggested by Hadden ’983 (Ans. 9 and 18—19; see FF 33—34 and 1—12). In
addition, Examiner reasons that “it would [have been] obvious to administer
the various treatments on the same day as a matter of convenience” (Ans. 9;
see FF 34). We find no error in Examiner’s prima facie case.
Appellant contends that Examiner failed to “establish[] that one of
ordinary skill in the art would have had a reasonable expectation of success
based on the cited art of inducing an immune response to an exogenous
antigen upon administering NCM, a thymic peptide, and the exogenous
antigen to a subject” (App. Br. 26—27 (citing Naylor Decl.)). We are not
persuaded.
Hadden ’519’s claimed method comprises the administration of NCM
and an exogenous antigen to treat a patient having advanced prostate cancer,
wherein the NCM acts as an adjuvant with the at least one exogenous tumor
antigen and stimulates an immune response to the at least one exogenous
tumor antigen in the patient (FF 33; see also FF 34). Hadden ’983 discloses
the administration of a composition comprising NCM and thymosin-al to,
inter alia, “increase^ T lymphocyte levels in vivo, . . . improved survival
rate, [provide] more rapid recovery, or improvement or elimination of
symptoms and in cancer reduction of tumor mass” and further discloses that
the composition “may be used with other treatments to improve immune
function and treat cancer” (FF 9; cf. Spec. 17: 19-23). Thus,
notwithstanding Appellant’s contention to the contrary, when taken as a
whole Hadden ’519 in combination with Hadden ’983 provides a person of
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ordinary skill in this art with a reasonable expectation of success in inducing
an immune response to an exogenous antigen in a subject. See In re
O'Farrell, 853 F.2d at 903-904 (Fed. Cir. 1988) (“Obviousness does not
require absolute predictability of success ... all that is required is a
reasonable expectation of success”).
CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness-type double patenting.
The rejection of claim 33 under the judicially created doctrine of
obviousness-type double patenting as being unpatentable over the claims of
Hadden ’072 in view of Hadden ’983, Hadden ’94(a), and Eisenbach is
affirmed. Claims 34—38 and 40-50 are not separately argued and fall with
claim 33.
The rejection of claim 33 under the judicially created doctrine of
obviousness-type double patenting as being unpatentable over the claims of
Hadden ’517 in view of Hadden ’983 and Eisenbach is affirmed. Claims
34—38 and 40—50 are not separately argued and fall with claim 33.
The provisional rejection of claim 33 under the judicially created
doctrine of obviousness-type double patenting as being unpatentable over
the claims of Hadden ’779 in view of Hadden ’983 and Hadden ’94(a) is
affirmed. Claims 34—38 and 40-50 are not separately argued and fall with
claim 33.
The rejection of claim 33 under the judicially created doctrine of
obviousness-type double patenting as being unpatentable over the claims of
Hadden ’796 in view of Hadden ’983, Hadden ’94(a), and Eisenbach is
33
Appeal 2016-003340
Application 13/653,152
affirmed. Claims 34—38 and 40-50 are not separately argued and fall with
claim 33.
The rejection of claim 33 under the judicially created doctrine of
obviousness-type double patenting as being unpatentable over the claims of
Hadden ’519 in view of Hadden ’983 is affirmed. Claims 34—38 and 40-50
are not separately argued and fall with claim 33.
TIME PERIOD FOR RESPONSE
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
34