`
`Claim Chart Demonstrating that Claims 1-3, 5-9, 11, 13-17, 20, 22-25, and 28
`of the ʼ966 patent are Unpatentable as Obvious Over Bernasconi in View of
`INOMAX Label, Loh, and Goyal.
`
`
`
`U.S. Pat. No.
`8,282,966
`CLAIM 1
`A method of reducing
`the risk of occurrence
`of pulmonary edema
`associated with a
`medical treatment
`comprising inhalation
`of 20 ppm nitric
`oxide gas, said
`method comprising:
`(a) performing
`echocardiography to
`identify a child in
`need of 20 ppm
`inhaled nitric oxide
`treatment for
`pulmonary
`hypertension,
`wherein the child is
`not dependent on
`right-to-left shunting
`of blood;
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`See Sections (a)-(c) below for Claim 1.
`
`Bernasconi teaches that echocardiography is essential to
`identify and treat pediatric patients with conditions, such as
`pulmonary hypertension, that may be treated with inhaled nitric
`oxide (“iNO”).
`
`Ex. 1004 at 8.
`Bernasconi further teaches using 20 ppm iNO to treat
`pulmonary hypertension in children.
`
`Ex. 1004 at 12.
`
`INOMAX label teaches that echocardiography can be used to
`identify patients with pulmonary hypertension that may be
`
`
`
`1
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`treated with iNO.
`
`Ex. 1014 at 4.
`INOMAX label further teaches the FDA recommended dose for
`iNO treatment is 20 ppm.
`
`Ex. 1014 at 6.
`INOMAX label further teaches that iNO should not be used in
`patients dependent on right-to-left shunting of blood.
`
`Ex. 1014 at 4.
`Bernasconi teaches that there are negative effects of iNO in
`patients with left ventricular dysfunction (“LVD”) including a
`risk of causing pulmonary edema.
`
`Ex. 1004 at 8.
`
`Loh teaches measuring a baseline wedge pressure prior to
`administering iNO. (Wedge pressure may also be called
`pulmonary capillary wedge pressure (“PCWP”), pulmonary
`arterial wedge pressure (“PAWP”), or merely “wedge.” All the
`terms refer to the same concept). Loh further teaches that
`patients with LVD have a baseline wedge pressure that is
`greater than 20 mm Hg.
`
`
`(b) determining that
`the child identified in
`(a) has a pulmonary
`capillary wedge
`pressure greater than
`or equal to 20 mm Hg
`and thus has left
`ventricular
`dysfunction, so is at
`particular risk of
`pulmonary edema
`upon treatment with
`inhaled nitric oxide;
`and
`
`
`
`2
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`Ex. 1006 at 2780.
`
`Ex. 1006 at 2781.
`
`
`
`
`
`
`
`Ex. 1006 at Table 1.
`
`Additionally, Goyal teaches measuring wedge pressure in
`children.
`
`
`
`3
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`
`
`Ex. 1007 at 209.
`
`
`
`Ex. 1007 at Table 1.
`Bernasconi teaches that there are negative effects of iNO in
`patients with LVD, including a risk of causing pulmonary
`edema.
`
`
`
`
`
`
`4
`
`(c) excluding the
`child from inhaled
`nitric oxide treatment
`based on the
`determination that the
`child has left
`ventricular
`dysfunction and so is
`at particular risk of
`pulmonary edema
`upon treatment with
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`inhaled nitric oxide.
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`CLAIM 2
`The method of claim
`1, wherein the child is
`a neonate.
`
`Ex. 1004 at 8.
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 1.
`
`Bernasconi teaches the use of iNO treatment in neonates and
`the FDA recommended dose is 20 ppm iNO.
`
`Ex. 1004 at 3.
`
`INOMAX label teaches treating neonates with hypoxic
`respiratory failure and pulmonary hypertension with 20 ppm
`iNO.
`
`Ex. 1014 at 3.
`
`CLAIM 3
`The method of claim
`1, wherein step (b)
`comprises measuring
`the child's pulmonary
`capillary wedge
`
`Ex. 1014 at 6.
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 1.
`
`Loh teaches measuring wedge pressure prior to administering
`
`
`
`5
`
`
`
`U.S. Pat. No.
`8,282,966
`pressure.
`
`Bernasconi, INOMAX label, Loh, and Goyal
`iNO to determine baseline conditions. Loh further teaches that
`patients with LVD have a baseline wedge pressure greater than
`20 mm Hg.
`
`
`
`
`
`Ex. 1006 at 2780.
`
`
`Ex. 1006 at 2781.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`6
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`Ex. 1006 at Table 1.
`
`Additionally, Goyal teaches measuring wedge pressure in
`children.
`
`
`
`
`
`Ex. 1007 at 209.
`
`
`
`7
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`Ex. 1007 at Table 1.
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 1.
`
`Bernasconi teaches that negative effects of iNO treatment in
`patients with LVD can include not only pulmonary edema, but
`also rapid left heart failure.
`
`Ex. 1004 at 8.
`
`8
`
`CLAIM 5
`The method of claim
`1, wherein the child is
`determined to be at
`particular
`risk not
`only of pulmonary
`edema, but also of
`other
`Serious
`Adverse Events, upon
`treatment
`with
`inhaled nitric oxide,
`and
`the
`child
`is
`excluded
`from
`inhaled nitric oxide
`treatment based on
`the determination that
`the child has
`left
`ventricular
`dysfunction and so is
`at particular risk not
`only of pulmonary
`edema, but also of
`other
`Serious
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`Adverse Events, upon
`treatment
`with
`inhaled nitric oxide.
`CLAIM 6
`A method of reducing
`the risk of occurrence
`of pulmonary edema
`associated with a
`medical treatment
`comprising inhalation
`of 20 ppm nitric
`oxide gas, said
`method comprising:
`(a) carrying out a
`diagnostic process
`comprising
`measuring blood
`oxygen level, to
`identify a child as
`being in need of 20
`ppm inhaled nitric
`oxide treatment for
`hypoxic respiratory
`failure, wherein the
`child is not dependent
`on right-to-left
`shunting of blood;
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`See Sections (a)-(c) for Claim 6 below.
`
`Bernasconi teaches the FDA recommended dose for treating
`hypoxic respiratory failure is 20 ppm.
`
`Ex. 1004 at 3.
`
`INOMAX label teaches the FDA recommended dose for iNO
`treatment is 20 ppm.
`
`Ex. 1014 at 6.
`
`INOMAX label teaches clinical trials measured a patient’s
`arterial blood gas before allowing the patient to be randomized
`for iNO treatment for hypoxic respiratory failure.
`
`
`
`
`
`9
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`(b) determine
`determining that the
`child has a pulmonary
`capillary wedge
`pressure greater than
`or equal to 20 mm Hg
`and thus has left
`ventricular
`dysfunction, so is at
`particular risk of
`pulmonary edema
`upon treatment with
`inhaled nitric oxide;
`and
`
`Ex. 1014 at 2, 3.
`INOMAX label further teaches that iNO should not be used in
`patients dependent on right-to-left shunting of blood.
`
`Ex. 1014 at 4.
`Bernasconi teaches that there are negative effects of iNO in
`patients with LVD including a risk of causing pulmonary
`edema.
`
`Ex. 1004 at 8.
`
`Loh teaches measuring a baseline wedge pressure prior to
`administering iNO. Loh further teaches that patients with LVD
`have a baseline wedge pressure that is greater than 20 mm Hg.
`
`Ex. 1006 at 2780.
`
`
`
`
`
`10
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`Ex. 1006 at 2781.
`
`
`
`
`
`Ex. 1006 at Table 1.
`
`Additionally, Goyal teaches measuring wedge pressure in
`children.
`
`
`
`
`
`11
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`Ex. 1007 at 209.
`
`
`
`Ex. 1007 at Table 1.
`Bernasconi teaches that there are negative effects of iNO in
`patients with LVD, including a risk of causing pulmonary
`edema.
`
`
`
`Ex. 1004 at 8.
`
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 6.
`
`
`12
`
`(c) excluding the
`child from treatment
`with inhaled nitric
`oxide based on the
`determination that the
`child has left
`ventricular
`dysfunction and so is
`at particular risk of
`pulmonary edema
`upon treatment with
`inhaled nitric oxide.
`CLAIM 7
`The method of claim
`6, wherein the
`diagnostic process of
`step (a) further
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`comprises performing
`echocardiography.
`
`Bernasconi, INOMAX label, Loh, and Goyal
`Bernasconi teaches that echocardiography is essential to
`identify and treat pediatric patients with conditions, such as
`pulmonary hypertension, that may be treated with iNO.
`
`Ex. 1004 at 8.
`
`INOMAX label teaches that echocardiography can be used to
`identify patients with hypoxic respiratory failure that may be
`treated with iNO.
`
`CLAIM 8
`The method of claim
`6, wherein the child is
`a neonate.
`
`Ex. 1014 at 4.
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 6.
`
`Bernasconi teaches the use of iNO treatment in neonates and
`the FDA recommended dose is 20 ppm iNO.
`
`Ex. 1004 at 3.
`
`INOMAX label teaches treating neonates with hypoxic
`respiratory failure or pulmonary hypertension with 20 ppm
`iNO.
`
`Ex. 1014 at 3.
`
`13
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`CLAIM 9
`The method of claim
`6, wherein step (b)
`comprises measuring
`the child's pulmonary
`capillary wedge
`pressure.
`
`Ex. 1014 at 6.
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 6.
`
`Loh teaches measuring the wedge pressure prior to
`administering iNO to determine baseline conditions. Loh
`further teaches that patients with LVD have a baseline wedge
`pressure greater than 20 mm Hg.
`
`
`
`
`
`Ex. 1006 at 2780.
`
`Ex. 1006 at 2781.
`
`
`
`
`
`
`
`
`
`
`14
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`Ex. 1006 at Table 1.
`
`Additionally, Goyal teaches measuring wedge pressure in
`children.
`
`
`
`
`
`Ex. 1007 at 209.
`
`
`
`15
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`Ex. 1007 at Table 1.
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 6.
`
`Bernasconi teaches that negative effects of iNO treatment in
`patients with LVD can include not only pulmonary edema, but
`also rapid left heart failure.
`
`Ex. 1004 at 8.
`
`
`
`
`
`
`
`
`
`16
`
`CLAIM 11
`The method of claim
`6, wherein the child is
`determined to be at
`particular risk not
`only of pulmonary
`edema, but also of
`other Serious
`Adverse Events, upon
`treatment with
`inhaled nitric oxide,
`and the child is
`excluded from
`inhaled nitric oxide
`treatment based on
`the determination that
`the child has left
`ventricular
`dysfunction and so is
`at particular risk not
`only of pulmonary
`edema, but also other
`Serious Adverse
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`Events, upon
`treatment with
`inhaled nitric oxide.
`
`CLAIM 13
`A method of
`treatment comprising:
`(a) performing
`echocardiography to
`identify a plurality of
`children who are in
`need of 20 ppm
`inhaled nitric oxide
`treatment for
`pulmonary
`hypertension,
`wherein the children
`are not dependent on
`right-to-left shunting
`of blood;
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`
`
`
`
`
`
`See Sections (a)-(e) for Claim 13 below.
`
`Bernasconi teaches that echocardiography is essential to
`identify and treat pediatric patients with conditions, such as
`pulmonary hypertension, that may be treated with iNO.
`
`Ex. 1004 at 8.
`Bernasconi further teaches using 20 ppm iNO to treat
`pulmonary hypertension in children.
`
`Ex. 1004 at 12.
`
`INOMAX label teaches that echocardiography can be used to
`identify patients with pulmonary hypertension that may be
`treated with iNO.
`
`Ex. 1014 at 4.
`INOMAX label further teaches the FDA recommended dose for
`iNO treatment is 20 ppm.
`
`
`
`
`17
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`(b) determining that a
`first child of the
`plurality has a
`pulmonary capillary
`wedge pressure
`greater than or equal
`to 20 mm Hg and
`thus has left
`ventricular
`dysfunction, so is at
`particular risk of
`pulmonary edema
`upon treatment with
`inhaled nitric oxide;
`
`Ex. 1014 at 6.
`INOMAX label further teaches that iNO should not be used in
`patients dependent on right-to-left shunting of blood.
`
`Ex. 1014 at 4.
`Bernasconi teaches that there are negative effects of iNO in
`patients with LVD including a risk of causing pulmonary
`edema.
`
`Ex. 1004 at 8.
`
`Loh teaches measuring a baseline wedge pressure prior to
`administering iNO. Loh further teaches that patients with LVD
`have a baseline wedge pressure that is greater than 20 mm Hg.
`
`Ex. 1006 at 2780.
`
`Ex. 1006 at 2781.
`
`
`
`
`
`
`
`18
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`Ex. 1006 at Table 1.
`
`Additionally, Goyal teaches measuring wedge pressure in
`children.
`
`
`
`
`
`Ex. 1007 at 209.
`
`
`
`19
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`Ex. 1007 at Table 1.
`Bernasconi teaches that echocardiography is essential to
`identify and treat pediatric patients with conditions that may be
`treated with iNO and identifying conditions that may
`contraindicate iNO.
`
`
`
`(c) determining that a
`second child of the
`plurality does not
`have left ventricular
`dysfunction;
`
`Ex. 1004 at 8.
`
`Loh teaches measuring a baseline wedge pressure prior to
`administering iNO. Loh further teaches that patients with LVD
`have a baseline wedge pressure that is greater than 20 mm Hg.
`
`Ex. 1006 at 2780.
`
`Ex. 1006 at 2781.
`
`20
`
`
`
`
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`Ex. 1006 at Table 1.
`
`Additionally, Goyal teaches measuring wedge pressure in
`children.
`
`
`
`
`Ex. 1007 at 209.
`
`21
`
`
`
`
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`Ex. 1007 at Table 1.
`Bernasconi teaches using 20 ppm iNO to treat pulmonary
`hypertension in children.
`
`
`
`Ex. 1004 at 12.
`INOMAX label teaches the FDA recommended dose for iNO
`treatment is 20 ppm.
`
`Ex. 1014 at 6.
`Bernasconi teaches that there are negative effects of iNO in
`patients with LVD, including a risk of causing pulmonary
`edema.
`
`Ex. 1004 at 8.
`
`22
`
`(d) administering the
`20 ppm inhaled nitric
`oxide treatment to the
`second child; and
`
`(e) excluding the first
`child from treatment
`with inhaled nitric
`oxide, based on the
`determination that the
`first child has left
`ventricular
`dysfunction, so is at
`particular risk of
`pulmonary edema
`upon treatment with
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`inhaled nitric oxide.
`CLAIM 14
`The method of claim
`13, wherein step (a)
`further
`comprises
`measuring
`blood
`oxygen levels in the
`first
`and
`second
`children and thereby
`determining that the
`first
`and
`second
`children are hypoxic.
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 13.
`
`INOMAX label teaches clinical trials measured a patient’s
`arterial blood gas before allowing the patient to be randomized
`for iNO treatment for hypoxic respiratory failure.
`
`CLAIM 15
`The method of claim
`13, wherein the
`second child has
`congenital heart
`disease.
`
`Ex. 1014 at 2, 3.
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 13.
`
`Bernasconi teaches that 20 ppm iNO treatment is effective in
`selectively lowering pulmonary vascular resistance in children
`with pulmonary hypertension and congenital heart disease.
`
`Ex. 1004 at 12.
`
`
`
`
`23
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`CLAIM 16
`The method of claim
`13, wherein step (b)
`comprises measuring
`the first child's
`pulmonary capillary
`wedge pressure.
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 13.
`
`Loh teaches measuring the wedge pressure prior to
`administering iNO to determine baseline conditions. Loh
`further teaches that patients with LVD have a baseline wedge
`pressure greater than 20 mm Hg.
`
`
`
`
`
`Ex. 1006 at 2780.
`
`Ex. 1006 at 2781.
`
`
`
`
`
`
`
`
`
`
`
`
`24
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`Ex. 1006 at Table 1.
`
`Additionally, Goyal teaches measuring wedge pressure in
`children.
`
`
`
`
`
`Ex. 1007 at 209.
`
`
`
`25
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`
`Ex. 1007 at Table 1.
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 13.
`
`Bernasconi teaches that echocardiography may be used to
`confirm a diagnosis and conduct therapy with iNO, as well as
`to exclude a condition that may contraindicate the use of iNO.
`
`Ex. 1004 at 8.
`Bernasconi further teaches that there are negative effects of
`iNO in patients with LVD, including a risk of causing
`pulmonary edema.
`
`Ex. 1004 at 8.
`
`26
`
`CLAIM 17
`The method of claim
`13, wherein
`determining that the
`second child of the
`plurality does not
`have pre-existing left
`ventricular
`dysfunction
`comprises performing
`echocardiography.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`CLAIM 20
`The method of claim
`13, wherein the first
`child is determined to
`be at particular risk
`not only of
`pulmonary edema,
`but also of other
`Serious Adverse
`Events, upon
`treatment with
`inhaled nitric oxide,
`and the first child is
`excluded from
`inhaled nitric oxide
`treatment based on
`the determination that
`the first child has left
`ventricular
`dysfunction and so is
`at particular risk not
`only of pulmonary
`edema, but also other
`Serious Adverse
`Events, upon
`treatment with
`inhaled nitric oxide.
`CLAIM 22
`A method of
`treatment comprising:
`(a) identifying a
`plurality of children
`who are in need of 20
`ppm inhaled nitric
`oxide treatment,
`wherein the children
`
`
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 13.
`
`Bernasconi teaches that negative effects of iNO treatment in
`patients with LVD can include not only pulmonary edema, but
`also rapid left heart failure.
`
`Ex. 1004 at 8.
`
`
`See Sections (a)-(e) of Claim 22 below.
`
`Bernasconi teaches that echocardiography is essential to
`identify and treat pediatric patients with conditions, such as
`pulmonary hypertension, that may be treated with iNO.
`
`27
`
`
`
`U.S. Pat. No.
`8,282,966
`are not dependent on
`right-to-left shunting
`of blood;
`
`Bernasconi, INOMAX label, Loh, and Goyal
`Ex. 1004 at 8.
`Bernasconi further teaches using 20 ppm iNO to treat
`pulmonary hypertension in children.
`
`Ex. 1004 at 12.
`
`INOMAX label teaches that echocardiography can be used to
`identify patients with pulmonary hypertension that may be
`treated with iNO.
`
`Ex. 1014 at 4.
`INOMAX label further teaches the FDA recommended dose for
`iNO treatment is 20 ppm.
`
`Ex. 1014 at 6.
`INOMAX label further teaches that iNO should not be used in
`patients dependent on right-to-left shunting of blood.
`
`Ex. 1014 at 4.
`Bernasconi teaches that there are negative effects of iNO in
`patients with LVD including a risk of causing pulmonary
`edema.
`
`Ex. 1004 at 8.
`
`28
`
`(b) in the first child of
`the plurality,
`measuring pulmonary
`capillary wedge
`pressure to determine
`that the first child of
`the plurality has a
`pulmonary capillary
`wedge pressure
`greater than or equal
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`to 20 mm Hg and
`thus has left
`ventricular
`dysfunction, so is at
`particular risk of
`pulmonary edema
`upon treatment with
`inhaled nitric oxide;
`
`Bernasconi, INOMAX label, Loh, and Goyal
`Loh teaches measuring a baseline wedge pressure prior to
`administering iNO. Loh further teaches that patients with LVD
`have a baseline wedge pressure that is greater than 20 mm Hg.
`
`Ex. 1006 at 2780.
`
`Ex. 1006 at 2781.
`
`
`
`
`
`
`
`Ex. 1006 at Table 1.
`
`
`
`
`
`29
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`Additionally, Goyal teaches measuring wedge pressure in
`children.
`
`
`
`
`
`Ex. 1007 at 209.
`
`Ex. 1007 at Table 1.
`Bernasconi teaches that echocardiography is essential to
`identify and treat pediatric patients with conditions that may be
`treated with iNO and identifying conditions that may
`contraindicate iNO.
`
`
`
`Ex. 1004 at 8.
`
`30
`
`(c) in the second
`child of the plurality,
`performing
`echocardiography
`and/or measurement
`of pulmonary
`capillary wedge
`pressure to determine
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`that the second child
`of the plurality does
`not have left
`ventricular
`dysfunction;
`
`Bernasconi, INOMAX label, Loh, and Goyal
`Loh teaches measuring a baseline wedge pressure prior to
`administering iNO. Loh further teaches that patients with LVD
`have a baseline wedge pressure that is greater than 20 mm Hg.
`
`
`
`
`
`
`
`Ex. 1006 at 2780.
`
`Ex. 1006 at 2781.
`
`Ex. 1006 at Table 1.
`
`
`
`
`
`31
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`Additionally, Goyal teaches measuring wedge pressure in
`children.
`
`
`
`
`
`Ex. 1007 at 209.
`
`Ex. 1007 at Table 1.
`Bernasconi teaches using 20 ppm iNO to treat pulmonary
`hypertension in children.
`
`
`
`Ex. 1004 at 12.
`INOMAX label teaches the FDA recommended dose for iNO
`treatment is 20 ppm.
`32
`
`(d) administering the
`20 ppm inhaled nitric
`oxide treatment to the
`second child; and
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`(e) excluding the first
`child from treatment
`with inhaled nitric
`oxide, based on the
`determination that the
`first child has left
`ventricular
`dysfunction, so is at
`particular risk of
`pulmonary edema
`upon treatment with
`inhaled nitric oxide.
`CLAIM 23
`The method of claim
`22, wherein step (a)
`comprises performing
`echocardiography to
`determine that the
`first and second
`children have
`pulmonary
`hypertension.
`
`Ex. 1014 at 6.
`Bernasconi teaches that there are negative effects of iNO in
`patients with LVD, including a risk of causing pulmonary
`edema.
`
`Ex. 1004 at 8.
`
`
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 22.
`
`Bernasconi teaches that echocardiography is essential to
`identify and treat pediatric patients with conditions, such as
`pulmonary hypertension, that may be treated with iNO.
`
`Ex. 1004 at 8.
`
`INOMAX label teaches that echocardiography can be used to
`identify patients with pulmonary hypertension that may be
`treated with iNO.
`
`Ex. 1014 at 4.
`
`
`33
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`CLAIM 24
`The method of claim
`22, wherein step (a)
`comprises measuring
`blood oxygen levels
`in the first and second
`children and thereby
`determining that the
`first and second
`children are hypoxic.
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 22.
`
`INOMAX label teaches clinical trials measured a patient’s
`arterial blood gas before allowing the patient to be randomized
`for iNO treatment for hypoxic respiratory failure.
`
`CLAIM 25
`The method of claim
`22, wherein
`the
`second
`child
`has
`congenital
`heart
`disease.
`
`Ex. 1014 at 2, 3.
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 22.
`
`Bernasconi teaches that 20 ppm iNO treatment is effective in
`selectively lowering pulmonary vascular resistance in children
`with pulmonary hypertension and congenital heart disease.
`
`Ex. 1004 at 12.
`
`
`
`
`
`
`34
`
`
`
`
`
`U.S. Pat. No.
`8,282,966
`CLAIM 28
`The method of claim
`22, wherein the first
`child is determined to
`be at particular risk
`not only of
`pulmonary edema,
`but also of other
`Serious Adverse
`Events, upon
`treatment with
`inhaled nitric oxide,
`and the first child is
`excluded from
`inhaled nitric oxide
`treatment based on
`the determination that
`the first child has pre-
`existing left
`ventricular
`dysfunction and so is
`at particular risk not
`only of pulmonary
`edema, but also other
`Serious Adverse
`Events, upon
`treatment with
`inhaled nitric oxide.
`
`
`
`
`
`
`Bernasconi, INOMAX label, Loh, and Goyal
`
`
`All the elements of the independent claim from which this
`claim depends are disclosed in Bernasconi, INOMAX label,
`Loh, and Goyal as outlined above in Claim 22.
`
`Bernasconi teaches that negative effects of iNO treatment in
`patients with LVD can include not only pulmonary edema, but
`also rapid left heart failure.
`
`Ex. 1004 at 8.
`
`35
`
`
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
