Ex Parte Filicori

Patent Trial and Appeal Board

Oct 26, 2017

11898470 (P.T.A.B. Oct. 26, 2017)

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.
11/898,470 09/12/2007 Marco Filicori 033236-0146 2438
22428 7590 10/30
Foley & Lardner LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
EXAMINER
DEBERRY, REGINA M
ART UNIT PAPER NUMBER
1647
NOTIFICATION DATE DELIVERY MODE
10/30/2017 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
ipdocketing @ foley. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARCO FILICORI
Appeal 2016-001545
Application 11/898470
Technology Center 1600
Before DONALD E. ADAMS, DEMETRA J. MILLS, and
RYAN H. FLAX, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134. The Examiner has rejected
claims 1—14 for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm and enter a new ground of rejection.
Appeal 2016-001545
Application 11/898,470
STATEMENT OF CASE
Claim 1 is the only independent claim on appeal, is representative, and
is reproduced below, along with claim 3, which is also relevant:
1. A single pharmaceutical composition consisting essentially
of FSH and hCG in a pharmaceutically acceptable carrier, wherein the
amount of FSH and hCG is selected from the group consisting of:
(i) 50 IU FSH and 100 IU hCG;
(ii) 50 IU FSH and 200 IU hCG;
(iii) 75 IU FSH and 25 IU hCG;
(iv) 75 IU FSH and 75 IU hCG;
(v) 75 IU FSH and 100 IU hCG;
(vi) 150 IU FSH and 25 IU hCG
(vii) 150 IU FSH and 75 IU hCG
(viii) 150 IU FSH and 100 IU hCG; and
(ix) 150 IU FSH and 10 IU hCG.
3. The pharmaceutical composition of claim 1 wherein the
amount of FSH and hCG is selected from the group consisting of (i)
50 IU FSH and 100 IU hCG and (ii) 50 IU FSH and 200 IU hCG.
Cited References
Skrabanja et al. US 5,656,597 Aug. 12, 1997
(hereinafter “Skrabanja ‘597”)
Skrabanja et al. US 5,929,028 July 27, 1999 (hereinafter
“Skrabanja ‘028”)
Menezo WO 00/022303 A2 Mar. 2, 2003
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Application 11/898,470
Hillier et al. US 2005/0049199 A1 Mar. 3, 2005
Franks et al. WO 00/67778 Nov. 16,2000
Kimberly A. Thompson et al., Gonadotropin requirements of the developing
follicle, 63 Fertility and Sterility 273-76 (1995).
Marco Filicori et al., Low-dose human chorionic gonadotropin therapy can
improve sensitivity to exogenous follicle-stimulating hormone in patients with
secondary amenorrhea, 72 Fertility and Sterility 1118-20 (1999)
(hereinafter “Filicori 1999”).
M. Filicori et al., Modulation of folliculogenesis and steroidogenesis in
women by graded menotrophin administration, 17 Human Production,
2009-15 (2002) (hereinafter “Filicori 2002”).
Grounds of Rejection
1. Claims 1, 2, 4—13, and 14 stand rejected under 35 U.S.C. § 103(a)
as being unpatentable over Menezo in view of Skrabanja ‘028.
2. Claims 1—3, 6, 8, and 11 stand rejected under 35 U.S.C. § 103(a) as
being unpatentable over Hillier.
3. Claims 1, 2, and 6—12 stand rejected under 35 U.S.C. § 103(a) as
being unpatentable over Thompson in view of Filicori 1999.
FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Final Action at
pages 6—28. Unless otherwise noted herein, we agree with and adopt the
Examiner’s findings of fact.
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PRINCIPLES OF LAW
In this Decision, we apply the preponderance of the evidence
standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427 (Fed. Cir.
1988) (explaining the general evidentiary standard for proceedings before
the Office).
In analyzing obviousness, “[t]he combination of familiar elements
according to known methods is likely to be obvious when it does no more
than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
416(2007).
Obviousness Rejection 1 Menezo and Skrabanja ‘028
The Examiner stated:
Menezo teaches 25-1000 IU hCG/day, 50-100 IU of
hCG/day or 75—100 IU hCG/day (page 5, page 8, lines 24—31, page
9, lines 21—35 and page 11, lines 5—20) .... Menezo teaches the
use of urinary or recombinant hCG (page 16, lines 1—5) and the use
of urinary or recombinant FSH (page 18, lines 1—9).... Because
FSH and hCG is administered to patients via injection, it must be
in liquid form at some point.... In Example 1, Menezo teaches that
at day 7, the experimental group received 50-100 IU of hCG on a
daily basis in combination with 150 IU of recombinant FSH
(Examples, page 16).
Final Act. 7. Further, Menezo discloses:
LH, FSH and hCG used in the invention may be formulated for
administration by any convenient route, generally in association
with a pharmaceutically acceptable carrier, diluent or excipient.
Appropriate formulations and routes of administration are well
known and documented in the art for LH, FSH and hCG and any
appropriate route and formulation may be used. Thus, the
pharmaceutical compositions of the invention generally contain a
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Application 11/898,470
pharmaceutically acceptable carrier, diluent or excipient, together
with the appropriate active ingredient.
Menezo 14,1. 33 — 15,1. 3. The Examiner acknowledged that, “Menezo
does not teach a single pharmaceutical composition consisting essentially of
FSH and hCG. Menezo does not teach said formulation in single pre-filled
syringes, vials or cartridges.” Final Act. 8. The Examiner relied on
Skrabanja ‘028, stating:
gonadotropin-containing formulations comprising FSH or
hCG or mixtures thereof (abstract; column 3, lines 15—26; column
3, lines 59—65; column 4, lines 22—30). Skrabanja [‘028] et al.
teach methods of admixing in an aqueous solution at least one
gonadotropin (column 5, lines 62—67). Skrabanja [‘028] et al.
teach that the formulation may be supplied in cartridges, ampoule,
vials, bottles or bags and that the cartridge may contain an amount
of the liquid gonadotropin formulation corresponding to one or
more therapeutic dosages (column 6, lines 56—67...).
Id. at 8. The Examiner concluded that:
It would [have been] obvious to one of skill in the art at the
time the invention was made to modify 75—200 FSH/day or 150 IU
FSH/day and 25-1000 IU hCG/day or 50-100 IU hCG/day or 75-
100 IU hCG/day, as taught by Menezo, by formulating it as a
single composition and supplying the pharmaceutical in pre-filled
syringes, vials or cartridges as taught by Skrabanja [‘028] et al.
with a reasonable expectation of success. The motivation and
expected success is provided by Menezo and Skrabanja [‘028].
Menezo states that the invention relates to administering low doses
of hCG with FSH during the stimulatory phase in [controlled
ovarian hyperstimulation (COH)]. Menezo teaches ranges of IU
hCG to be employed in conjunction with ranges of IU FSH. A
single pharmaceutical composition comprising FSH and hCG
would provide an expedient manner of delivery to patients.
Because Menezo teaches parenteral administration of FSH and
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hCG, it would be obvious to supply the formulation in devices to
inject the drug, as taught by Skrabanja [‘028] et al.
Id. at 8—9.
Appellant contends that, as explained in the Filicori Declaration,
Menezo is not a fixed dose study, and argues that:
it would not be useful in the context of Menezo Example 1
to have a single composition with specified amounts of FSH and
hCG. In accordance with Menezo Example 1, “the doses would
have been selected and tailored to each patient and individually
adjusted during the study based on each patient’s response.”
Filicori Declaration, 110. When such flexibility is required, the
skilled artisan would not find it useful to have a single combination
composition comprising specific, predetermined amounts of both
FSH and hCG. Filicori Declaration, 115. Thus, contrary to the
assertion at page 9 of the Office Action, it would not have been
“expedient” to prepare a composition as claimed for use in a
method according to Example 1 of Menezo.
App. Br. 12 (citing Marco Filicori Declaration dated May 12, 2011 (“Filicori
Declaration”)). Appellant further argues that, in the Mannaerts Declaration,
Dr. Mannaerts points out that Menezo itself emphasizes the
need for “such customization and care” with regard to hCG at
pages 10—11 of Menezo, where “Menezo warns that due to the
long half-life of hCG ‘when multiple doses are used care must be
taken that accumulation does not lead to undesirably high [serum]
levels,’ which could lead to ‘premature luteinisation.’” Mannaerts
Declaration, |10 (quoting Menezo).
Id. at 13 (citing Bernadette Mannaerts Declaration dated Apr. 10, 2014
(“Mannaerts Declaration”)). Appellant argues that the Examiner ignored the
countervailing concerns that a skilled artisan would have faced, as discussed
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Application 11/898,470
in the Sjogren Declaration. Id. at 18 (citing Helen Sjogren Declaration dated
July 25, 2014); see also Sjogren Declaration || 4—6. Dr. Sjogren states that:
A person of ordinary skill in the field would be reluctant to
combine different pharmaceutical compositions without knowing
in advance that the active and inactive components are both
compatible and non-reactive. For example, such a person would
have concerns that one or more excipients in one composition
might react with one or more excipients in the other composition.
For example, lactose (which is present in the Bravelle and
Fostimon FSH products) is incompatible with amino acids like L-
methionine (which is present in the Ovidrel hCG product). If a
composition comprising lactose were mixed with a composition
comprising an amino acid, a Maillard reaction could occur.
Sjogren Declaration |5.
The Examiner responds to Appellant’s arguments, taking the position
that:
The claims are directed to a composition, not a method of
administering fixed doses. Therefore, it would not matter if the
prior art changes doses from one day to the next since any one
dose is the single composition as currently claimed. In the instant
case, Menezo clearly teaches in Example 1 that 150—200 IU
FSH/day was administered with 50—100 IU hCG/day. Menezo
teaches those ranges. If 150 IU FSH/day and 100 IU hCG/day was
selected and tailored to an individual patient, it would be obvious
to combine 150 IU FSH and 100 IU hCG in a single
pharmaceutical composition. Menezo states that the invention
relates to administering low doses of hCG with FSH during the
stimulatory phase in COH. A single pharmaceutical composition
comprising FSH and hCG would provide an expedient manner of
delivery to patients versus administering FSH then administering
hCG. Skrabanja [‘028] et al. teach single pre-filled syringes, vials
or cartridges comprising FSH and hCG. The Examiner notes that
multiphasic (i.e. biphasic or triphasic) birth control pills are an
example of a pharmaceutical wherein the administered dose is not
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a fixed dose. Biphasic or triphasic birth control pills contain
different amounts of estrogen and progestin. The amount of
estrogen and progestin in the pill differs from day to day or week
to week. However, any one dose of a single birth control pill
composition comprising estrogen and progestin is still taught. In
view of the foregoing, when all of the evidence is considered, the
totality of the rebuttal evidence of nonobviousness fails to
outweigh the evidence of obviousness.
Ans. 7—8.
ANALYSIS
We vacate ground of rejection 3 set forth in the Grounds of Rejection
above, as we find rejection 3 cumulative to rejection 1. We vacate rejection
2 in favor of the New Ground of Rejection, included herein and discussed in
detail below.
With respect to rejection 1, we agree with the Examiner’s fact finding,
statement of the rejection and responses to Appellant’s arguments as set
forth in the Answer with respect to rejection 1. We find that the Examiner
has provided evidence to support a prima facie case of obviousness. We
provide the following additional comments on the Examiner’s
determinations as set forth in the Final Rejection and Answer.
Menezo discloses a composition having ranges of FSH and hCG for
use in COH that overlap Appellant’s claimed ranges. Menezo 6,11. 21—26.
Menezo discloses administering hCG and rFSH in combination. Id. at 19
(Example 1). Menezo provides for a “kit for use in COH comprising 12 or
more, preferably 14 or more daily doses of FSH, preferably about 75—200 IU
FSH/day, more preferably about 150 IU FSH/day, and 4 to 8, 5 to 8 or 6 to 8
daily doses of hCG, for example 4, 5, 6, 7 or 8 daily doses of hCG, 25
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preferably about 25-1000 IU hCG/day, more preferably about 50-100 IU
hCG/day.” Id. at 6,11. 20-26. Menezo discloses administration protocols
where FSH and hCG are administered on the same day. Id. (Tables 1—3).
We agree with the Examiner that it would have been obvious to one of
ordinary skill in the art at the time of the invention to prepare a pharmaceu­
tical dosage including a combination of FSH and hCG in at least one of the
specifically claimed dosages because Menezo discloses that those of
ordinary skill in the art routinely select dosages of FSH and hCG within the
ranges disclosed in Menezo for use in controlled ovarian hyperstimulation.
Id. at 1. Several of the claimed dosages fall within the suitable dosage
ranges disclosed in Menezo. In analyzing patentability here, the prior art’s
disclosure of just one combined dosage recited in claim 1 is all that is
required to meet the claim requirements. Selecting a narrow range from
within a somewhat broader dosage range disclosed in a prior art reference is
no less obvious than identifying a range that simply overlaps a disclosed
range. In fact, when, as here, the claimed dosage ranges are completely
encompassed by the prior art, the conclusion of obviousness is even more
compelling than in cases of mere overlap. The normal desire of scientists or
artisans to improve upon what is already generally known provides the
motivation to determine where in a disclosed set of percentage ranges is the
optimum combination of percentages. See In re Boesch, 617 F.2d 272, 276
(CCPA 1980) (“[Djiscovery of an optimum value of a result effective
variable in a known process is ordinarily within the skill of the art.”
(citations omitted)).
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Skrabanja ‘028 discloses that FSH and hCG may be administered in a
single dosage form, dissolved together, and provided in a sterile liquid
formulation, e.g., a cartridge, ampoule, vial, bottle or bag.. Skrabanja ‘028
col. 6,11. 34—65. The rejection before us is not an anticipation rejection, but
is based on what would have been obvious to one of ordinary skill in the art.
As noted by the Court in KSR, “[a] person of ordinary skill is also a person
of ordinary creativity, not an automaton.” KSR, 127 S. Ct. at 1742.
Appellant has not provided persuasive evidence that a person of ordinary
skill in the art, knowing that the two compounds FSH and hCG can be
administered simultaneously, would not have found it obvious to administer
the compounds in a single dosage form, as taught by Skrabanja ‘028, in the
(routine) dosage ranges disclosed in Menezo and as claimed.
Appellant argues that:
As explained in the Filicori Declaration, however, Example
1 of Menezo is not a fixed dose study, and so it would not be
useful in the context of Menezo Example 1 to have a single
composition with specified amounts of FSH and hCG. In
accordance with Menezo Example 1, “the doses would have been
selected and tailored to each patient and individually adjusted
during the study based on each patient’s response.” Filicori
Declaration, |10. When such flexibility is required, the skilled
artisan would not find it useful to have a single combination
composition comprising specific, predetermined amounts of both
FSH and hCG. Filicori Declaration, |15.
App. Br. 12. As discussed above, it would have been routine for those of
ordinary skill in the art to tailor dosages of FSH and hCG within the specific
dosage ranges disclosed in Menezo. It was also well known in the art to
combine FSH and hCG in a single, admixed formulation. Skrabanja ‘028
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col. 4,11. 23—25. It is not inconsistent with customized care to select from
prepared pharmaceutical dosage forms in kits (see, e.g., Menezo 6,11. 21—26)
having the desired dosage combinations within conventional dosage ranges.
Appellant argues that:
In her Declaration, Dr. Mannaerts also points out that
“Menezo does not provide detailed, patient-level information on
the [Example 1] study.” Mannaerts Declaration, |9. Thus,
contrary to the presumption behind the rejection, “it cannot be
known whether any subject was administered 150 IU FSH and 100
IU hCG on the same day.” Id.
App. Br. 12. However, the rejection before us is not an anticipation
rejection and the reference need not specifically disclose the claimed FSH,
hCG dosages so long as at least one of the claimed dosages would have been
rendered obvious. The rejection is based on what would have been obvious
to one of ordinary skill in the art and, as discussed above, it would have been
routine for those of ordinary skill in the art to tailor dosages of FSH and
hCG within the specific dosage ranges disclosed in Menezo to improve the
disclosed therapy. It was also well known in the art to combine FSH and
hCG in a single formulation in a kit. Menezo 6,11. 21—26. Furthermore, the
Examiner is correct that the claims are not directed to a specific
administration protocol or method of administration, they are directed to a
composition and such a composition would have been obvious in view of the
cited prior art combination.
We note, the Sjogren Declaration (| 5) states:
A person of ordinary skill in the field would be reluctant to
combine different pharmaceutical compositions without knowing
in advance that the active and inactive components are both
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compatible and non-reactive. For example, such a person would
have concerns that one or more excipients in one composition
might react with one or more excipients in the other composition.
For example, lactose (which is present in the Bravelle and
Fostimon FSH products) is incompatible with amino acids like L-
methionine (which is present in the Ovidrel hCG product). If a
composition comprising lactose were mixed with a composition
comprising an amino acid, a Maillard reaction could occur.
However, Menezo does not disclose the inclusion of either lactose or
methionine in their gonadotropin formulations. Skrabanja ‘028 does not
disclose formulations including lactose. Thus, concerns over lactose
reactions are not determinative here.
As stated, supra, the Examiner has presented a prima facie case of
obviousness that remains unrebutted by Appellant’s evidence based on a
preponderance of the evidence of record. Therefore, the obviousness
rejection 1 is affirmed for the reasons of record.
NEW GROUND OF REJECTION
Claim 3, was not originally included in rejection 1, which otherwise
made cumulative the other two rejections made by the Examiner. We enter
a new ground of rejection of claim 3 under 35 U.S.C. § 103(a) as being
unpatentable over Menezo in view of Skrabanja ‘028 and Skrabanja ‘597.
Claim 3 recites, “[t]he pharmaceutical composition of claim 1 wherein
the amount of FSH and hCG is selected from the group consisting of (i) 50
IU FSH and 100 IU hCG and (ii) 50 IU FSH and 200 IU hCG.”
Menezo is discussed above in relation to the invention defined by
independent claim 1, but the reference does not disclose a dosage of FSH as
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low as 50 IU of FSH. Skrabanja ‘028 discloses that “a combination of FSH
and . . . HCG are dissolved together to from [sic] a formulation having
therapeutic amount of both of the selected gonadotropins.” Skrabanja ‘028
col. 6,11. 42-45. Further, Skrabanja ‘028 discloses a range of FSH dosages,
from 50-225 IU. Id. col. 6,11. 23—25. Skrabanja ‘028 further discloses that
“[approximately 75 IU [FSH] is considered a therapeutic amount.” Id. col.
6,11. 22—24. Skrabanja ‘028 discloses that useful “doses of gonadotropins
are known to medical practitioners, and the amount included in a dose is
generally dependent upon the disease state and the particular patient being
treated.” Id. col. 6,11. 18—22.
Skrabanja ‘597 discloses a well-known and preferred dosage of FSH
in the art is 50 IU FSH. Skrabanja ‘597 claim 1, col. 1,11. 44—50).
Skrabanja ‘597 also discloses combinations of hCG and FSH. Id. col. 1,11.
22—27. It would have been obvious to one of ordinary skill in the art to
prepare a combination dosage of FSH and hCG comprising 50 IU of FSH
and 100 or 200 IU of hCG because such dosages were well known in the
COH and gonadotropin delivery art in view of the disclosures of Menezo,
Skrabanja ‘028 and Skrabanja ‘597. Therefore, we enter a new ground of
rejection for claim 3 for this reason.
CONCLUSION OF LAW
The cited references support the Examiner’s obviousness rejection 1,
which is affirmed for the reasons of record.
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We vacate rejection 3 set forth in the Grounds of Rejection, as we
find rejection 3 to be cumulative to rejection 1. We vacate rejection 2 in
favor of the New Ground of Rejection, as set forth above.
TIME PERIOD FOR RESPONSE
Regarding the affirmed rejection(s), 37 C.F.R. § 41.52(a)(1) provides
“Appellant may file a single request for rehearing within two months from
the date of the original decision of the Board.”
In addition to affirming the Examiner’s rejection(s) of one or more
claims, this decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.”
37 C.F.R. § 41.50(b) also provides that the Appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment of
the claims so rejected or new evidence relating to the claims so
rejected, or both, and have the matter reconsidered by the
examiner, in which event the proceeding will be remanded to
the examiner....
(2) Request rehearing. Request that the proceeding be reheard
under § 41.52 by the Board upon the same record....
Should the Appellant elect to prosecute further before the Examiner
pursuant to 37 C.F.R. § 41.50(b)(1), in order to preserve the right to seek
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review under 35 U.S.C. §§ 141 or 145 with respect to the affirmed rejection,
the effective date of the affirmance is deferred until conclusion of the
prosecution before the Examiner unless, as a mere incident to the limited
prosecution, the affirmed rejection is overcome.
If the Appellant elects prosecution before the Examiner and this does
not result in allowance of the application, abandonment or a second appeal,
this case should be returned to the Patent Trial and Appeal Board for final
action on the affirmed rejection, including any timely request for rehearing
thereof.
AFFIRMED and NEW GROUND UNDER 41.50(b)
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