Ex Parte Ljungblad et al

Patent Trial and Appeal Board

Aug 15, 2016

12995062 (P.T.A.B. Aug. 15, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/995,062 02/15/2011 Ulf L jungblad
95280 7590 08/15/2016
Johnson, Marcou & Isaacs, LLC
317 A East Liberty Street
Savannah, GA 31401
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
ITH-2400US 7601
EXAMINER
ARON, KIMBERLY A
ART UNIT PAPER NUMBER
1633
MAILDATE DELIVERY MODE
08/15/2016 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 ULF LJUNGBLAD,
YEN BACKSTROEM LUNDGREN,
and OLA WINQVIST
Appeal2014-006653
Application 12/995,062
Technology Center 1600
Before FRANCISCO C. PRATS, JEFFREYN. FREDMAN, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a method
of treating viral disease in a patient and composition. The Examiner rejected
the claims as indefinite, as anticipated, and as obvious. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Party in Interest as ITH, Immune
Therapy Holdings AB (see Br. 3).
Appeal2014-006653
Application 12/995,062
Statement of the Case
Background
"CD4+ T cells are key regulators of immunological responses and
have a crucial role in maintaining immune competence. These cells are also
the primary target for HIV" (Spec. 1:11-13). "It has been reported that
GnRH [gonadotropin releasing hormone] not only exhibits hormonal effects
but also stimulates the immune system" (Spec. 2:3--4).
The Claims
Claims 1-13, 16-24, and 26-30 are on appeal. Independent claims 1
and 18 are representative and read as follows:
1. A method of treating viral disease in a patient,
comprising the concomitant administration of:
Gonadotropin Releasing Hormone (GnRH), a GnRH
analog, or a pharmaceutically acceptable salt thereof in an
amount sufficient to maintain an unphysiological plasma
level of the GnRH or the GnRH analog in the patient; and,
at least one natural, semi-synthetic, or synthetic sexual
hormone, wherein the natural, semi-synthetic, or synthetic
sexual hormone is administered in an amount sufficient to
compensate for the castrative effect of the GnRH or the
GnRH analog.
18. A composition for treating viral disease comprising:
an amount of Gonadotropin Releasing Hormone
(GnRH) or GnRH analog sufficient to maintain
unphysiological plasma level of the GnRH or the GnRH
analog in a patient;
an amount of at least one natural, semi-synthetic, or
synthetic sexual hormone sufficient to compensate for the
castrative effect of the GnRH or the GnRH analog in the
patient;
and a pharmaceutically acceptable carrier.
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Application 12/995,062
The Issues
A. The Examiner rejected claims 1, 18, and 23 under 35 U.S.C. § 112,
second paragraph (Ans. 6).
B. The Examiner rejected claims 18, 19, 21, 22, and 27 under 35 U.S.C.
§ 102(b) as anticipated by Swerdloff2 (Ans. 6-7).
C. The Examiner rejected claims 1-10, 12, 13, 16-24, and 26-30 under
35 U.S.C. § 103(a) as obvious over Boyd,3 Engel,4 and Schultze-Mosgau5
(Ans. 7-11).
D. The Examiner rejected claims 1-12, 16-24, 26, and 27 under
35 U.S.C. § 103(a) as obvious over Boyd, Engel, Schultze-Mosgau, and
Swerdloff (Ans. 11-12).
A. 35 U.S.C. § 112, second paragraph
The Examiner finds that claims 1, 18, and 23 recite "the limitation
'the castrative effect of the GnRH or the GNRH analog' in line 9. There is
insufficient antecedent basis for this limitation in the claim" (Ans. 6).
2 Swerdloff et al., Developments in the control of testicular
function, 6 Balliere' s Clin. Endocrinology Metabolism 451--483
(1992) ("Swerdloff').
3 Boyd et al., US 2008/0279812 Al, published Nov. 13, 2008
("Boyd").
4 Engel et al., US 2004/0138138 Al, published July 15, 2004
("Engel").
5 Schultze-Mosgau et al., New developments in the use of
peptide gonadotropin-releasing hormone antagonists versus
agonists, 14 Expert Opin. Investig. Drugs 1085-1097 (2005)
("Schultze-Mosgau").
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Appellants "submit that the amendments to claims 1, 8, and 23 filed in
response to the Final Office Action of January 11, 2013 overcome this
rejection" (Br. 10).
Because the Examiner denied entry of the after-final amendments in
the Advisory action mailed July 3, 2013, the amendments were not made
and the claim language lacking antecedent basis remains. We therefore
affirm the Examiner's indefiniteness rejection.
B. 35 U.S.C. § 102(b) over Swerdloff
The Examiner finds that "Swerdloff discloses compositions
comprising GnRH agonists and testosterone. See, page 457, second full
paragraph. Swerdloff references Heber & Swerdloff, which in the cited
references sections of Swerdloff (at page 478) shows that the androgen of
the Heber & Swerdloff reference is testosterone" (Ans. 7).
Appellants contend that
in the passage cited by the Office, Swerdloff actually teaches a
"GnRH agonists combined with androgens suppress
spermatogenesis but produce azoospermia in only about half
the subjects tested." (Final Office Action of January 11, 2013,
pages 2-3, items 7, 8 and 9). Thus, rather than having a
formulation that suppresses castrative effects, this passage
actually teaches a composition that leads to castrative effects, in
that suppression of spermatogenesis would be considered
castration.
(Br. 11 ). Appellants contend that "[t ]he features of claim 18 are simply not
found in Swerdloff either directly or inherently as required" (Br. 12).
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Application 12/995,062
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that Swerdloff anticipates the
composition of claim 18?
Findings of Fact
1. Swerdloff teaches "GnRH agonists combined with androgens
suppress spermatogenesis but produce azoospermia in only about half the
subjects tested" (Swerdloff 457).
2. Swerdloff teaches that the "regimen of combined daily
injections of7.5 mg ofNaI-Glu GnRH and bimonthly injections of
testosterone enanthate for 16 weeks led to reversible azoospermia in seven
of eight subjects while maintaining libido and sexual potency" (Swerdloff
458).
Principles of Law
Inherency, however, may not be established by probabilities or
possibilities. The mere fact that a certain thing may result from
a given set of circumstances is not sufficient. If, however, the
disclosure is sufficient to show that the natural result flowing
from the operation as taught would result in the performance of
the questioned function, it seems to be well settled that the
disclosure should be regarded as sufficient. ...
Inherency is not necessarily coterminous with the knowledge of
those of ordinary skill in the art. Artisans of ordinary skill may
not recognize the inherent characteristics or functioning of the
prior art.
MEHL/Biophile Intern. Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir.
1999) (internal citations omitted).
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Analysis
We begin with claim interpretation. We interpret the phrase
"sufficient to compensate for the castrative effect of the GnRH" as imposing
a functional requirement on the composition such that administration of the
composition to a patient does not result in complete chemical castration of
that patient.
However, Appellants do not identify, and we do not find, any specific
details or other information regarding ranges of amounts of either GnRH or
sexual hormone in the Specification that specifically delimit amounts
necessary to achieve the functional requirement of "sufficient to compensate
for the castrative effect of the GnRH." These amounts are therefore
unconstrained by claim 18 or by any teaching in the Specification.
Thus, disclosure in the prior art of concurrent administration of GnRH
and a sexual hormone in amounts that mitigate, in some way, the castrative
effect of GnRH, either by failing to produce azoospermia in a patient or by
treating side effects due to GnRH, is reasonably interpreted as satisfying the
claim requirement of amounts "sufficient to compensate for the castrative
effect of the GnRH."
Applying this interpretation to the prior art, Swerdloff teaches "GnRH
agonists combined with androgens suppress spermatogenesis but produce
azoospermia in only about half the subjects tested" (FF 1). Thus, Swerdloff
teaches a composition comprising both GnRH and a sexual hormone, here
androgens, and the composition does not result in castration in half the
subjects (FF 1 ).
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Swerdloff therefore evidences that the composition necessarily, in
some specific patients, resulted in the inherent compensation for the
castrative effect of GnRH (FF 1 ), and therefore reasonably anticipates claim
18.
Appellants contend that "rather than having a formulation that
suppresses castrative effects, this passage actually teaches a composition that
leads to castrative effects, in that suppression of spermatogenesis would be
considered castration" (Br. 11 ).
We do not find this argument persuasive because all of the patients in
Swerdloff received concurrent administration of GnRH and androgens, and
some of these patients did not have castrative effects, satisfying the
requirement of the claim. That the composition had a different effect in a
different subset of patients does not overcome the inherent result that the
combination of GnRH and androgens was sufficient to inherently
compensate, at least to some degree, for the castrative effect of GnRH in
"about half the subjects tested" (FF 1 ).
Conclusion of Law
The evidence of record supports the Examiner's conclusion that
Swerdloff anticipates the composition of claim 18.
C. and D. 35 U.S.C. § 103(a) over Boyd, Engel, Schultze-Mosgau, and
Swerdloff
Because the same issues are dispositive for both of these rejections,
we will consider them together.
The Examiner finds it obvious
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Application 12/995,062
to combine the teachings of Boyd, directed to methods of
treating viral diseases by the administration of GnRH agonists
at levels sufficient to cause medical castration, with the
disclosure of Engle, showing that altering T cell populations
using GnRH agonists at levels sufficient to cause medical
castration produces many undesirable side effects, further with
the disclosure of Schultz[e]-Mosgau directed to the use of add-
back therapy in medical compositions comprising GnRH
agonist and therapies as ways to combat the well-known
undesirable side effects of GnRH agonist use.
(Ans. 9).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the prior art renders claim 1
obvious?
Findings of Fact
3. Boyd teaches "a method for preventing or diminishing the risk
of an infection, illness, or disease in a patient, the method comprising
disrupting sex steroid mediated signalling in the patient" (Boyd i-f 50).
4. Boyd teaches that in "some embodiments, the methods of the
invention are used to prevent or treat viral infections, such as HIV, herpes,
influenza, and hepatitis" (Boyd i-f 51 ).
5. Boyd teaches that "sex steroid mediated signaling may be
directly or indirectly blocked ... by the administration of modifiers of sex
hormone production, action, binding or signaling including, but not limited
to ... GnRH/LHRH" (Boyd i-f 59).
6. Engel teaches that:
In a patent by R. L. Boyd (WO 200062657, AU 200037977) the
aut[h ]or claims that disrupting the sex steroid signalling by
application of an LHRH-agonist will result in a modification of
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the T-cell population in subjects with a depressed or abnormal
T-cell population. This treatment will have the undesired side-
effect of castration of the subject ....
In men and pre-menopausal women the treatment would also
result in the typical symptoms of lowering the sex hormone-
level below castration level, e.g. hot flushes, women will
additionally be at risk to lose bone minerals
(Engel iTiT 2-3).
7. Schultze-Mosgau teaches that
GnRH agonists have become well-established tools for therapy
whenever temporary and fully reversible medical castration and
suppression of sex steroid secretion is required. . . . Although
the typical side effects (including headache, hot flushes, vaginal
dryness, mood disturbances and accelerated bone density loss)
of total oestradiol withdrawal for a longer period of time in
cancer treatment may be acceptable, complete oestrogen
deprivation should be avoided in benign conditions
(Schultze-Mosgau 1090, col. 1).
8. Schultze-Mosgau teaches that "potential side effects of medical
therapy have been effectively managed with 'add-back therapy' using low-
dose oestrogen and progestin combinations that limit their occurrence, while
still allowing a regression of endometriotic lesions and symptom-free
periods or maintaining reduced size of fibroids for a longer period of time"
(Schultze-Mosgau 1090, col. 1).
Principles of Law
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
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Application 12/995,062
KSR!nt'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability." Id. at 417.
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 7-11; FF 3-8) and agree that the
claims are rendered obvious by Boyd, Engel, and Schultze-Mosgau. We
address Appellants' arguments below.
Appellants
submit, however, that the "add back therapy" of Schultz[e]-
Mosgau would contravene and undermine the stated purpose of
Boyd. In other words, combining Schultz[e]-Mosgau with Boyd
would render Boyd unsatisfactory for its stated purpose. Such a
modification would not make any sense to one of ordinary skill
in the art given that the stated purpose of the stated purpose of
Boyd, is to disrupt or ablate sex steroids in the subject.
(Br. 14). Appellants "submit that one o[f] ordinary skill in the art reading
Boyd still would not fathom introducing sex steroids into at the same time
they were using GnRH or a GnRH analog to interfere with or ablate these
very sex hormones" (Br. 15).
We do not find this argument persuasive because it fails to address the
combined teachings of the references. Boyd does teach to disrupt sex steroid
mediated signaling (FF 3) for treatment of viruses (FF 4) with agents such as
GnRH (FF 5), but Engel directly refers to Boyd and suggests that Boyd's
method using GnRH results in unwanted side effects due to reduction in sex
hormone levels (FF 6). Schultze-Mosgau teaches that these unwanted side-
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effects of GnRH treatment may be mitigated by "add-back therapy" using
sexual hormones without ablating the therapeutic effect of the GnRH
treatment (FF 7-8).
Thus, when the references are considered together, Schultze-Mosgau
complements Boyd's teaching by suggesting an approach to mitigate
unwanted side effects resulting from Boyd's GnRH treatment by Engel (FF
3-8). Schultze-Mosgau's use of sexual hormones to mitigate side effects
would not have been expected to prevent GnRH therapeutic effect because
Schultze-Mosgau teaches that even with the "add-back therapy," the GnRH
treatment effects on fibroids and endometriotic lesions continue (FF 8).
Appellants contend that "Swerdloff teaches against the co-
administration of GnRH agonists and testosterone, a sexual hormone for the
purpose of treating a viral infection in which the testosterone is administered
in an amount-sufficient to compensate for the castrative effect of the GnRH
or the GnRH analog" (Br. 15).
We do not find this argument persuasive. Swerdloff teaches that
GnRH agonists may be combined with sexual hormones for chemical
castration (FF 1-2), but Swerdloff does not address Boyd's teaching that
treatment with GnRH will treat viral infections (FF 4) nor does Swerdloff
teach that Schultze-Mosgau's "add-back therapy" using sexual hormones
would fail to achieve the expected result of mitigating unwanted side-effects
(FF 8). Indeed, Swerdloff appears to include testosterone for "maintaining
libido and sexual potency" (FF 2), like the reasons given by Schultze-
Mosgau for combining a sexual hormone with GnRH to mitigate an
unwanted side effect: here the loss of libido and sexual potency.
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Appellants do not identify any teaching in Swerdloff that actually
criticizes, discredits, or discourages the use of a sexual hormone to mitigate
side effects in GnRH treatment. Indeed Swerdloff is reasonably understood
as suggesting such a combination for that purpose (FF 2). See In re Fulton,
391 F.3d 1195, 1201 (Fed. Cir. 2004) ("The prior art's mere disclosure of
more than one alternative does not constitute a teaching away from any of
these alternatives because such disclosure does not criticize, discredit, or
otherwise discourage the solution claimed").
Appellants contend that the references "do not support a reasonable
expectation of success for achieving the claimed invention, and in fact
Swerdloff teaches away from the claimed invention. Second, the result of
combining the cited reference with ordinary skill in the art was unpredictable
at the time of filing of the application" (Br. 16).
We are not persuaded. An "obviousness finding was appropriate
where the prior art 'contained detailed enabling methodology for practicing
the claimed invention, a suggestion to modify the prior art to practice the
claimed invention, and evidence suggesting that it would be successful."' In
re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re 0 'Farrell, 853
F.2d 894, 902 (Fed. Cir. 1988).
Here, Boyd provides a detailed enabling methodology for treatment of
viral infections with GnRH (FF 3-5) while Engel and Schultze-Mosgau
provide specific reasons to include sexual hormones to mitigate GnRH
symptoms (FF 6-8) and Schultze-Mosgau expressly teaches that sexual
hormones will function to mitigate GnRH symptoms while still permitting
the desired GnRH therapeutic effect (FF 8). These teachings provide a
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reasonable expectation of success. "'Obviousness does not require absolute
predictability of success ... all that is required is a reasonable expectation
of success."' Kubin, 561 F.3d at 1360 (citing In re 0 'Farrell, 853 F.2d at
903-904).
Conclusions of Law
The evidence of record supports the Examiner's conclusion that the
prior art renders claim 1 obvious.
SUMMARY
In summary, we affirm the rejection of claims 1, 18, and 23 under
35 U.S.C. § 112, second paragraph.
We affirm the rejection of claim 18 under 35 U.S.C. § 102(b) as
anticipated by Swerdloff. Claims 19, 21, 22, and 27 fall with claim 18.
We affirm the rejection of claim 1under35 U.S.C. § 103(a) as
obvious over Boyd, Engel, and Schultze-Mosgau. Claims 2-10, 12, 13, 16-
24, and 26-30 fall with claim 1.
We affirm the rejection of claim 1under35 U.S.C. § 103(a) as
obvious over Boyd, Engel, Schultze-Mosgau, and Swerdloff. Claims 2-12,
16-24, 26, and 27 fall with claim 1.
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
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