Ex Parte TULLOCH et al

Patent Trial and Appeal Board

Jul 11, 2018

13691677 (P.T.A.B. Jul. 11, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/691,677 11/30/2012
5251 7590 07/13/2018
SHOOK, HARDY & BACON LLP
INTELLECTUAL PROPERTY DEPARTMENT
2555 GRAND BL VD
KANSAS CITY, MO 64108-2613
FIRST NAMED INVENTOR
Simon J. TULLOCH
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.
MALL.288574 9366
EXAMINER
ROGERS, JAMES WILLIAM
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
07/13/2018 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
following e-mail address(es):
IPDOCKET@SHB.COM
IPRCDKT@SHB.COM
BPARKERSON@SHB.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SIMON J. TULLOCH and
WARRENW. WASIEWSKI 1
Appeal2017-000889
Application 13/691,677
Technology Center 1600
Before DEMETRA J. MILLS, ERIC B. GRIMES, and JEFFREY N.
FREDMAN, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to method
of treating hyperbilirubinemia in an infant, which have been rejected as
obvious. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
STATEMENT OF THE CASE
"Raised bilirubin levels may lead to potentially dangerous conditions,
particularly in infants. . . . Increased bilirubin levels may lead to
1 Appellants identify the Real Party in Interest as INF A CARE
PHARMACEUTICAL CORPORATION. Br. 2.
Appeal2017-000889
Application 13/691,677
hyperbilirubinemia which can be dangerous to a patient." Spec. ,r 2.
"Currently approved and commonly used treatments for hyperbilirubinemia
include phototherapy and exchange transfusion. . . . The decision to initiate
phototherapy is based on the newbom's age and total serum bilirubin level,
in conjunction with their risk level according to a nomogram approved by
the American Academy of Pediatricians (AAP)." Id. ,r 73.
"The present disclosure relates to methods of treating
hyperbilirubinemia with a metalloporphyrin." Id. ,r 3. "In some
embodiments, the metalloporphyrin is tin IV mesoporphyrin IX dichloride
(also called stannsoporfin or SnMP)." Id. ,r 173.
Claims 99-104, 106-114, 116-120, 122-132, 134--140, 142-145,
147-159, 161-173, and 176-181 are on appeal. Claim 99 is illustrative and
reads as follows:
99. A method of treating hyperbilirubinemia or the symptoms
thereof in an infant, the method comprising:
administering a therapeutic amount of stannsoporfin to the infant with
hyperbilirubinemia where no exclusion factor is present and at least one of a
baseline total bilirubin level is elevated above a predetermined threshold and
at least one risk factor is present;
wherein the predetermined threshold is below the threshold for
administration of phototherapy according to AAP guidelines;
determining post treatment total bilirubin levels following
administration of the stannsoporfin from about 6 and to about 72 hours after
administering the stannsoporfin to the infant to determine if phototherapy
should be initiated based upon the AAP guidelines; and
wherein the therapeutic amount of the stannsoporfin is from about
0.75 mg/kg to about 5 mg/kg of the infant's weight.
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The claims stand rejected as follows:
Claims 99--104, 106-114, 116-120, 122-132, 134--140, 142-145,
147-159, 161-173, and 176-181 under 35 U.S.C. § 103(a) as obvious based
on Martinez2 and American Academy of Pediatrics (AAP) 3 (Non-Final
Action4 3) and
Claims 99--104, 106-114, 116-120, 122-132, 134--140, 142-145,
147-159, 161-173, and 176-181 under 35 U.S.C. § 103(a) as obvious based
on Martinez, AAP, Kappas, 5 and Reddy6 (Non-Final Action 3--4).
DISCUSSION
The Examiner has rejected all of the claims on appeal as obvious
based on Martinez and AAP, or these same references combined with
Kappas and Reddy. The same issues are dispositive for both rejections.
The Examiner finds that Martinez discloses treating
hyperbilirubinemia in infants by administering stannsoporfin, where no
2 Jorge C. Martinez et al., Control of Severe Hyperbilirubinemia in Full-term
Newborns With the Inhibitor of Bilirubin Production Sn-Mesoporphyrin,
103 Pediatrics 1-5 (1999).
3 American Academy of Pediatrics, Management of Hyperbilirubinemia in
the Newborn Infant 35 or More Weeks of Gestation, 114 Pediatrics 297-316
(2004).
4 Office Action mailed May 1, 2015.
5 Attallah Kappas et al., Direct Comparison of Sn-Mesoporphyrin, An
Inhibitor of Bilirubin Production, and Phototherapy in Controlling
Hyperbilirubinemia in Term and Near-Term Newborns, 95 Pediatrics 468-
474 (1995).
6 Pradeep Reddy et al., Tin-Mesoporphyrin in the Treatment of Severe
Hyperbilirubinemia in a Very-Low-Birth-Weight Infant, 23 J. Perinatology
507-508 (2003).
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Application 13/691,677
exclusion factor is present and a risk factor is present. Final Action 7 5---6.
The Examiner also finds that Martinez discloses determining post-treatment
bilirubin levels every 24 hours. Id. at 6. The Examiner finds that Kappas
discloses "that administration to preterm infants within 24 hours of birth
SnMP (tin mesoporphyrin, e.g. stannsoporfin) in amounts of 6 mmol/kg
( examiner calculated amount to be 4.5 mg/kg) was effective in controlling
hyperbilibubinemia." Non-Final Action 4. We note that Kappas actually
describes administering 6 µmol/kg of stannsoporfin (Kappas 468, abstract
("SnMP ( 6 µmol/kg birth weight")), not 6 mmol/kg, but Appellants do not
dispute that Kappas' dosage of stannsoporfin is equivalent to 4.5 mg/kg. See
Br. 8-9.
The Examiner also finds that
AMERICAN ACADEMY OF PEDIATRICS 2004 teaches that
the prior art had known of nomogram (see Fig 3) for initiating
phototherapy approved by the AAP and reproduced (see instant
application, FIGURE 1 ), wherein the nomogram established
when phototherapy should be initiated based upon the infant's
measured total serum bilirubin level (mg/dL), the infant's age
in hours from birth, and the infant's risk level ( see instant
specification, [0077] and FIGURE 1 ).
Final Action 9-10.
The Examiner concludes that
the claimed invention would have been prima fascia [sic]
obvious to one of ordinary skill in the art because the
administering amounts of SnMP in the amounts claimed and
within the timeline claimed to pre-term infants for treatment of
hyperbilirubinemia was part of the ordinary capabilities of a
7 Office Action mailed Sept. 10, 2014.
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Application 13/691,677
person of ordinary skill in the art, in view of the disclosures of
Kappas and Reddy.
Non-Final Action 4.
We agree with the Examiner that the cited references support a prima
facie case of obviousness. Martinez discloses using stannsoporfin (SnMP)
to treat infants with plasma bilirubin concentrations (PBC) between 15
mg/ dL and 18 mg/ dL at 48-96 hours of age. Martinez 1, Abstract. Martinez
states that "[t]he infants' PBCs were followed by daily measurements." Id.
Martinez describes several factors that caused infants to be excluded
from the study. Id. at 2, "Study Population and Design." Martinez states
that "ABO incompatible infants who were Coombs-negative and had no
rapid bilirubin rise were included in both the control (n = 4) and SnMP-
treated (n = 6) groups." Id. Appellants' Specification states that risk factors
include ABO blood type incompatibility. Spec. ,r 7. Thus, Martinez's
treatment included infants with a risk factor, as recited in claim 99.
"Infants in the treated group received a single intramuscular dose of
SnMP (6 µmol/kg birth weight [BW]) 48 to 96 hours after birth." Id. at 2,
right col., last full paragraph. Kappas also teaches treating hyper-
bilirubinemia in infants by administering SnMP at a dosage of 6 µmol/kg
birth weight. Kappas 468 Abstract (Methods). The Examiner has calculated
that the amount administered by Kappas corresponds to 4.5 mg/kg. Non-
Final Action 4. Appellants do not dispute this finding. Br. 8-9. In any
event, Reddy expressly describes treating hyperbilirubinemia in an infant
using SnMP at a dose of 4.5 mg/kg. Reddy 307, last paragraph.
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AAP discloses "guidelines [that] provide a framework for the
prevention and management of hyperbilirubinemia in newborn infants."
AAP 297, Abstract. AAP's Figure 3 is reproduced below:
25 ----..-----..-----...---...,.-------- 42:8
1--1--~-~-....-+-.---+...-.---+--+-----1"---t--t-----t-------- ----------- ----
1--+-...;.;---I'·~~~~~~~~~~~ ~~~~~~~~~~~ ~~~~~~~~~~~ ~~~~~~~~~~~--~~~~~~~~-~ ~-----+----t--------,e----------,.-~~~~~~~~ ~~~~n~~~~~ ~~~~~~~~~~H ~~H
!hth 24 h 48 h 72 M 96 h 5 Days 6 Days 7 D.ays
Age
Figure 3 shows "[g]uidelines for phototherapy in hospitalized infants
of 35 or more weeks' gestation." AAP 304. AAP states that "intensive
phototherapy ... should be used when the TSB [total serum bilirubin]
exceeds the line indicated for each category." Id.
According to AAP, phototherapy should be used for infants at
medium risk (2: 3 8 weeks' gestation and risk factors) if their TSB level
exceeds 17 mg/ dL at an age of 96 hours. Martinez, however, discloses
treating infants who were delivered after at least 3 8 weeks' gestation, were
48-96 hours of age and had a plasma bilirubin concentration between 15
mg/dL and 18 mg/dL. Martinez 2, Study Population and Design ("[I]nfants
had to be healthy and delivered between 2:3 8 and :S41 weeks gestational age
(GA) after an uncomplicated pregnancy with a PBC between 2:256.5 µmol/L
(15 mg/dL) and :S307.8 µmol/L (18 mg/dL) 48 to 96 hours afterbirth.").
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Thus, Martinez's patients included some who were treated despite
being below the AAP threshold for phototherapy; for example, an infant 96
hours of age and a plasma bilirubin level between 15 mg/dL and 17 mg/dL.
It would have been obvious to treat such an infant as disclosed by Martinez,
because Martinez states that "[a] single dose of SnMP proved effective in
controlling severe hyperbilirubinemia in full-term breastfed newborns with
high bilirubin levels between 48 and 96 hours." Id. at Abstract
(Conclusion). Martinez also states that "SnMP eliminated the need for PT
[phototherapy] and reduced the use of medical resources in the clinical
treatment of this problem" (id.), providing an additional reason to choose its
treatment method.
Appellants argue that Martinez "fails to provide any teaching,
suggestion or motivation to administer stannsoporfin to an infant in a
therapeutic amount, let alone, wherein the therapeutic amount of the
stannsoporfin is from about 0. 75 mg/kg to about 5 mg/kg of the infant's
weight." Br. 8.
This argument is unpersuasive, because Martinez discloses
administering stannsoporfin at the same dosage level used by Kappas
(6 µmol/kg), and the Examiner finds that Kappas' dosage converts to 4.5
mg/kg, which, in any event, is expressly taught by Reddy.
Appellants also argue that "Martinez and American Academy of
Pediatrics also fail to provide any teaching, suggestion or motivation to
administer treatment when the infants' baseline total bilirubin level is below
the threshold for medical intervention (e.g., administering phototherapy)
according to the AAP guidelines as recited in claim 99." Br. 9. Appellants
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also argue that Martinez teaches using stannsoporfin as an alternative to
phototherapy, and would have consulted the 1994 AAP Guidelines because
those were the guidelines in effect at the time Martinez was published. Id.
Appellants conclude that
Id.
the skilled artisan would, at best, be motivated to administer
stannsoporfin to an infant based on the 1994 AAP nomogram
guidelines as a replacement for phototherapy but would not be
motivated to administer stannsoporfin to an infant whose
bilirubin levels are below the threshold for administration of
phototherapy according to the AAP nomogram guidelines.
These arguments are unpersuasive because, as discussed above,
Martinez suggests treating the group of infants who are 48-96 hours of age
and have plasma bilirubin levels of 15-18 mg/ dL. This group of infants
includes some who are below the threshold of the AAP Guidelines for
phototherapy; e.g., infants who are 96 hours old and have a plasma bilirubin
level of 15-17 mg/dL. It would have been obvious to treat these infants, like
all of the infants in Martinez's specified group, because Martinez discloses
that treatment with stannsoporfin was effective and eliminated the need for
phototherapy.
We disagree with Appellants' position that the 1994 AAP Guidelines,
rather than the 2004 AAP Guidelines cited by the Examiner, are the relevant
ones to consult regarding what would have been obvious to those of ordinary
skill in the art. The standard for obviousness is not what would have been
obvious at the time a prior art reference was published but whether "the
differences between the subject matter sought to be patented and the prior art
are such that the subject matter as a whole would have been obvious at the
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time the invention was made." 35 U.S.C. § 103(a) (emphasis added). The
effective filing date of the instant application is Dec. 1, 2011, and therefore
obviousness is assessed as of that date, not based on the time Martinez was
published.
Appellants also argue that "there is no teaching, suggestion or
motivation to administer a therapeutic dose of stannsoporfin, and in
particular, the claimed therapeutic dose of 1. 5 mg/kg to 3. 0 mg/kg, to an
infant with a bilirubin level below the threshold for administration for
phototherapy." Br. 11.
This argument is unpersuasive. The issue of treating infants who are
below the threshold of the AAP Guidelines has been discussed above. The
argument based on dosages of 1.5 mg/kg to 3.0 mg/kg is also unpersuasive
because Appellants have not identified, and we do not see, any claims on
appeal that are limited to those dosages, or that exclude the dosage of 4.5
mg/kg taught in the prior art.
Finally, Appellants argue that they have
surprisingly and unexpectedly shown that doses of less than 4.5
mg/kg (i.e. 1. 5 mg/kg and 3. 0 mg/kg) were effective in
reducing bilirubin levels in the infants treated and also reduced
the need for phototherapy. Perhaps most surprising is that
infants treated with lower doses of stannsoporfin were found to
have a lower incidence of subsequent phototherapy (see instant
application at paragraph [00306] and table 18 showing that only
17 .6% of subjects given 1.5 mg/kg required subsequent
phototherapy compared with 25% of those subjects given 4.5
mg/kg). In addition, where phototherapy was needed, its
duration was shorter in those infants given lower doses of
stannsoporfin (see instant application at paragraph [00308] and
table 20). Finally, and also surprising was the finding that
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discharge time was reduced with these lower doses ( see instant
application at paragraph [00308] and table 21 ).
Br. 8; see also id. at 12-13.
This argument and the cited evidence are unpersuasive for two
reasons. First, even if Appellants' results for doses of 1.5 mg/kg and 3.0
mg/kg were unexpected, none of the claims are limited to that range of
dosages, but instead read on the 4.5 mg/kg dose taught by the prior art.
Appellants' results, even if they were persuasive, are not commensurate in
scope with the claims. See In re Huai-Hung Kao, 639 F.3d 1057, 1068 (Fed.
Cir. 2011) ("Evidence of unexpected results must be reasonably
commensurate with the scope of the claims.").
In addition, Martinez discloses that "[t]he administration of a single
dose of SnMP entirely eliminated the need for PT [phototherapy ]; none of
the 40 infants in the SnMP-treated group required supplemental PT."
Martinez 3, right col., last paragraph. Thus, Appellants' results showing that
treatment with stannsoporfin at each of the three doses tested (1.5 mg/kg, 3.0
mg/kg, and 4.5 mg/kg) reduced but did not eliminate the need for
phototherapy are actually worse than what would have been expected based
on the prior art, which taught that a single 4.5 mg/kg dose completely
eliminated the need for phototherapy. The same is true of Appellants'
evidence showing shorter durations of phototherapy and quicker discharge
times for the stannsoporfin-treated groups as compared to placebo-treated
patients.
With regard to claim 127, Appellants argue that Martinez teaches
treatment "48 to 96 hours after birth (See Martinez, page 2, first column,
fifth paragraph) but not less than 48 hours after birth." Br. 13. Claim 127
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recites, among other things, that "the infant's age is less than about 48
hours." Br. 28 (Claims App.).
This argument is unpersuasive, because both the range in Martinez
(48-96 hours) and the range of claim 127 ("less than about 48 hours,"
emphasis added) include the value of 48 hours. See In re Peterson, 315 F .3d
1325, 1329 (Fed. Cir. 2003) ("In cases involving overlapping ranges, ...
even a slight overlap in range establishes a prima facie case of
obviousness.").
Claim 127 also recites, among other things, that "at least one risk
factor is present; wherein the at least one risk factor is selected from
hemolytic disease, anti-C Rh incompatibility, anti-c Rh incompatibility,
anti-D Rh incompatibility, anti-E Rh incompatibility, anti-e Rh
incompatibility, G6PD deficiency and combinations thereof." Br. 28
(Claims App.). Appellants argue that "Kappas teaches away from the
administration of a therapeutic amount of stannsoporfin to an infant with
these risk factors. Specifically, Kappas excluded infants with these risk
factors (See Kappas page 469, first column, second paragraph)." Br. 15.
This argument is also unpersuasive, because it is unsupported by the
evidence. Kappas discloses that female infants can be difficult to classify as
having a normal level or a deficiency of the enzyme G6PD. Kappas 469,
left col., second paragraph. However, Kappas also states that "[ w ]e elected
to include in Study I only male newborns, whose classification as either
G-6-PD deficient or normal was unequivocal." Id.
Thus, Kappas discloses that infants who were deficient in G6PD were
included in its study. Kappas therefore expressly suggests at least one of the
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risk factors recited in claim 127. We therefore affirm the rejection of claim
127.
Finally, with regard to claim 127, Appellants repeat their argument
based on unexpected results. Br. 15-16. This argument is unpersuasive for
the reasons discussed above with respect to claim 99.
With regard to claim 154, Appellants argue that Martinez "provides
no teaching suggestion or motivation to administer within 36 hours of birth
of the infant." Br. 16. Claim 154 recites, among other things, that
"administering a therapeutic amount of the stannsoporfin is performed
within 36 hours of birth of the infant." Br. 32 (Claims App.). Appellants
argue that "American Academy of Pediatrics and Kappas fail to cure this
deficiency" because "neither Martinez, American Academy of Pediatrics or
Kappas to provide any teaching, suggestion, or motivation for the
administration of a therapeutic amount of stannsoporfin to an infant, who's
[sic] bilirubin levels are below the threshold levels determined by the AAP
nomogram for initiating phototherapy." Id. at 16.
This argument is not persuasive. Kappas states that "[i]nfants
presenting between 36 and 84 hours of age and with plasma bilirubin levels
[in a certain range] were eligible for enrollment" and "neonates in this study
were enrolled in the time period from 36 to 84 hours after birth." Kappas,
legend to Figure 3 and right col. Thus, Kappas discloses that administering
stannsoporfin to an infant 36 hours after birth is an effective treatment for
hyperbilirubinemia. See id. at 468, right col., third paragraph ("[A] single
dose of SnMP administered at the time when PT would customarily be
initiated at The Metera Maternity Hospital was able to entirely supplant the
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requirement for light treatment in the newborn populations studied.").
Based on this disclosure, it would have been obvious to modify Martinez's
method to begin treatment with stannsoporfin in infants presenting with
hyperbilirubinemia within 3 6 hours of birth.
Appellants' argument regarding administering stannsoporfin to an
infant with a bilirubin level below the threshold of the AAP Guidelines is
addressed above in the discussion of claim 99. Appellants also repeat, with
regard to claim 154, their argument based on evidence of unexpected results.
Br. 1 7. That argument is also addressed above in the discussion of claim 99.
We therefore affirm the rejection of claim 154.
Claims 100-104, 106-114, 116-120, 122-126, 128-132, 134--140,
142-145, 147-153, 155-159, 161-173, and 176-181 fall with claims 99,
127, and 154. 37 C.F.R. § 4I.37(c)(l)(iv).
SUMMARY
We affirm both of the rejections.
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
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