United States District Court, D. New Jersey
MEMORANDUM AND ORDER
G. SHERIDAN, U.S.D.J.
matter comes before the Court on Joint Claim Construction
submitted by Amag Pharmaceuticals, Inc. (“AMAG”
or “Plaintiffs”) and Sandoz, Inc.
(“Sandoz” or “Defendant”) pursuant to
L. Pat. R. 4.3 (see D.I. 38).
order to market and sell pharmaceutical drug
Feraheme®, AMAG has listed the following U.S.
Patents-6, 599, 498 (the “'498 patent); 7, 553, 479
(the “'479 patent); 7, 871, 597 (the
“'597 patent”); 8, 591, 864 (the
“'864 patent”); and 8, 926, 947 (the
“'947 patent”) (collectively
“Patents-in-Suit”)-in Food and Drug
Association's (“FDA”) Approved Drug Products
with Therapeutic Equivalence Applications, commonly known as
the Orange Book. See 21 U.S.C. § 355(B)(1).
Feraheme® is used to treat iron deficiencies
in people with chronic kidney disease.
Sandoz filed an Abbreviated New Drug Application
(“ANDA”) with the FDA in order to seek approval
to market a generic version of Feraheme®.
See 21 U.S.C. § 355(j)(1). Accordingly,
pursuant to 21 U.S.C. § 355(j)(5)(B)(iii), AMAG
initiated this suit against Sandoz because Sandoz's
request to market the generic version of
Feraheme® was done prior to the expiration of
April 26-27, 2017, pursuant to L. Pat. R. 4.6, a
Markman hearing was conducted before the Court for
multiple claim terms recited in the Patents-in-Suit. These
terms are construed below.
(ferumoxytol) is an FDA approved pharmaceutical drug approved
for the use of treating iron deficiencies in people with
chronic kidney disease (“CKD”).
Feraheme® is administered either as a bolus or
as an intravenous solution. (See the '498
patent, col. 3, ll. 17-19 and 29).
The Patent Family
the Patents-in-Suit, the '498 patent is the parent patent
as it issued from the first-filed patent application. The
'479 and '597 patents claim priority to the '498
patent as their respective patent applications are
continuation-in-part patent applications of the '498
patent. As such, the disclosure of the '479
and '597 patents include additional subject matter that
is not disclosed in the '498 matter.
the patent application of the '864 patent is a
continuation application of the U.S. Patent 8, 501, 158, whose
patent application is a divisional application of the '597
patent. As such, the disclosure of the '864 patent is the
same as the disclosure of the '597 patent because no new
matter is added to the '864 patent. Likewise, the
'947 patent shares the same disclosure as the '864
and '597 patent because it is a continuation application
of the '864 patent.
short, the three patents with three distinct,
non-overlapping, disclosures are-the '498 patent, the
'479 patent, and the '597 patent. The disclosures of
the '864 and '947 patents are the same as the
The '498 Patent A. Disclosure of the
'498 patent is directed towards pharmaceutical
compositions that are used for providing enhanced magnetic
resonance imaging (“MRI”) of a patient's
internal organs, such as liver, spleen, or lymph nodes,
during an MRI scan. The compositions are imaging agents that
comprise carboxyalklayed reduced polysaccharides coated
ultra-small superparamagnetic iron oxides. (See
Abstract of the '498 patent).
'498 patent identifies that the conventional contrast
agents are distributed into two classes of imaging
agents-namely, low molecular weight gadolinium complexes such
as Magnevist® and colloidal iron oxides. The
conventional contrast agents face the following
problems-expense, inefficiency, loss of coating of sterilized
agent by autoclaving, narrow range of organ uptake for
purposes of imaging. (Id. at col. 1, ll. 25-35).
During the autoclaving process, for example, the polymer
coating becomes dissociated from the iron oxide cores due to
exposure to heat. The polymer dissociation results in
functional consequences, such as, physical changes in the
material (i.e., clumping), bio-distribution changes (i.e.,
changes in plasma half-life), and changes in toxicity profile
(i.e., potential increases in adverse events). (Id.
at col. 7, ll. 60-65).
order to mitigate dissociation of the coating from the iron
oxide when the material is subject to heat stress, the
'498 patent discloses a method for the synthesis of a
colloid of an iron oxide that is associated with a water
soluble polysaccharide coating. (Id. at col. 10, ll.
30-35). The term “heat stress” being defined as
“heating the colloid to approximately
121°C or higher for about 30 minutes at
neutral pH […] that are well known in the art to
autoclave (or terminally sterilize) an injectable
drug.” (Id. at col. 10, ll. 35-40).
example embodiment, the '498 patent discloses that a
coated colloid may be prepared by adding a polysaccharide to
an iron oxide sol (a colloidal dispersion in a liquid).
Wherein the term “colloid” includes “any
macromolecule or particle having a size less than about 250
nm [(nanometer)]”. The iron oxide polysaccharide
colloids of the invention have improved physical
characteristics and manufacturability such as ability to
withstand heat stress and show less evidence of
polysaccharide dissociation under stress. (Id. at
col. 11, ll. 5-20).
colloids of the '498 patent can be used as contrast
agents for MRI scanning or in other applications such as
magnetic fraction of cells, immunoassays, magnetically
targeted drug delivery, and as therapeutic injectable iron
supplements. (Id. at col. 11, ll. 40-45). In
particular, the colloids are suited for parenteral
administration because the final sterilization is
autoclaving. Autoclaving being a preferred method because it
eliminates viability of all cellular life forms including
bacterial spores and viruses. (Id. at col. 11, ll.
the improvements provided in these colloids that can be used
as contrast agents over the prior art include-(i) heat
sterilization by autoclaving that optimizes long-term storage
at ambient temperatures; (ii) being non-toxic to mammals,
including humans, at higher doses; and (iii) ability to
obtain additional images during a single clinical visit and
use of the imaging apparatus due to successive doses being
administered after a brief interval after administration of a
first dosage. (Id. at col. 11, ll. 60-67-col. 12,
to the various example embodiments, the '498 patent
discloses that a reduced polysaccharide iron oxide complex or
a derivatized reduced polysaccharide iron oxide complex,
which is a reduced polymer of glucose, is produced by
sterilizing the same by autoclaving. An example of a reduced
polymer of glucose is a reduced dextran. (Id. at
col. 2, ll. 1-15). In another example embodiment, the
'498 patent discloses that a complex such as a reduced
derivatized polysaccharide iron oxide complex may be stable
at a temperature of at least approximately 100°C or
121°C. (Id. at col. 5-20).
'498 patent includes a total of 26 claims, wherein claims
1, 13, 23 and 25 are independent claims. Claims 1 and 23
being method claims and claims 13 and 25 being product
Prosecution History of the '498 Patent
Applicant's Arguments/Remarks filed October 9,
response to the July 5, 2001 non-final Office action, the
Applicant responded by arguing that none of the cited
references disclosed a “reduced polysaccharides”
or “carboxyalkylated polysaccharides” such as
reduced carboxymethylated dextran as required in then pending
claims 1-13, 18-29-35-36, 39-52 and 57-66. (See
Image File Wrapper of the '498 Patent; Applicant's
Arguments/Remarks at 6-7, filed October 9, 2001).
Additionally, with respect to a particular reference cited
against the claimed invention, Applicant argued that there
was no disclosure of autoclavability of the MRI contrast
agents. (Id. at 8). With respect to then claims
18-20 and 29, the Applicant argued that the methods and
compositions are “stable after autoclaving, with
respect to certain physical and chemical properties (e.g.,
stability at particular elevated temperatures, or stability
of colloidal suspensions without aggregation), ” which
were not disclosed by any of the prior art references.
(Id. at 9).
in the same response, in order to distinguish the claimed
invention over the cited art, the Applicant equates the term
“complex” to “polysaccharide, ” by
arguing that “Golman et al. neither teaches nor
suggests autoclaving, either of a polysaccharide or of a
complex.” (Id. at 11).
Applicant's Arguments/Remarks filed April 25,
in response statements made on April 25, 2002, the Applicant
noted that preamble “for administration to a mammalian
subjection, ” would be understood by one of ordinary
skill in the art to mean that “the iron oxide complex
must have an acceptable profile with respect to stability and
risk of adverse reaction, and if the mammal is a human, must
typically be approved by a regulatory authority such as the
Food and Drug administration.” (See
Applicant's Arguments/Remarks at 4, filed April 25,
2002). Further, in order to distinguish over the cited art,
the Applicant primarily relies on an affidavit of one of the
co-inventors of the '498 patent.
to 37 C.F.R. § 1.132, in support of its response, the
Applicant submitted an affidavit of Dr. Jerome Lewis. Dr.
Lewis is a co-inventor of polysaccharide superparamagnetic
iron oxide complexes and related materials and methods.
(Id. at Declaration of Jerome Lewis (“Decl. of
Lewis”) at ¶ 1). Dr. Lewis noted that from a
regulatory and commercial perspective, to have a
“polysaccharide superparamagnetic iron oxide complex as
a pharmaceutical that when terminally sterilized (autoclaved)
does not form particulates and that has minimal edematous
response.” (Id. at ¶ 3). Terminal
sterilization (autoclaving) being favored over filter
sterilization because-(i) terminal sterilization provides a
much higher level of sterility assurance; and (ii) their
opaque nature prevents ordinary visual inspection by the
physician during administering the drug, thereby making
terminal sterilization more desirable. (Id. at
¶¶ 4-5 (internal citations omitted)).
declaration, Dr. Lewis provides a background on the
development of these types of pharmaceutical drugs. In
particular, he notes that the drug disclosed in the present
application is a third generation drug. The two previous
generation drugs had issues. The first generation drug was
Feridex® disclosed in U.S. Patent 4, 827, 945.
The material used in Feridex® had issues such
as particulate formulation and adverse reactions such as
edematous response (i.e., accumulation of an excessive amount
of watery fluid in cells, tissues, or body cavities).
(Id. at ¶ 7). The second generation drug being
Combidex®, a complex of ultra-small particles.
This drug is filtered by a process of filtration, instead of
terminal sterilization, at the time it is administered to the
patient. The risks with this drug being-edematous response,
administration of the material only after dilution, and slow
the first and second generation drugs, this third generation
drug, which is a complex of ultra-small particles and has a
favorable bio-distribution, has sufficiently small risk of
particulate formulation such that no filtration is required
during administration. (Id. at ¶¶ 7-9).
And, because of low risk of adverse reaction, the drug
disclosed in the '498 patent can be administered more
rapidly and without dilution. (Id. at ¶ 10). In
short, Dr. Lewis notes that the new material disclosed in the
'498 patent is sterilized using the autoclaving method.
And, unlike the conventional drugs, Combidex®
and Feridex®, the new material does not
require filtration during administration, no dilution, no
slow administration, and no edematous response. Accordingly,
noting that such properties are commercially and medically
desirable in an iron based colloidal MRI contrast agent.
(Id. at ¶ 11).
distinguishing the third generation agent disclosed in the
'498 patent from the conventional drugs, Dr. Lewis states
that “autoclaving normally requires temperatures of at
least 121 degrees [C] (see, for example, Exhibit C), and in
any event at least 115 degrees C.” (Id. at
¶ 15). Dr. Lewis notes that the material disclosed in
the prior art references, noted in the Office action dated
November 2, 2001, namely, Lewis and Groman references, are
autoclaved in the presence of citrate. Doing so has a risk of
particulate formulation requiring administration through a
filter, and an adverse reaction risk requiring dilution and
slow administration. (Id. at ¶ 15). In other
words, the cited references fail to teach anything about
creating a material without degradation or decreased risk of
adverse reactions. (Id.)
the section titled “Consideration of Certain Terms in
the Patent Application, ” Dr. Lewis notes, “[i]n
the present invention, the reduced polysaccharide is a poly
alcohol compound; thus, it contains multiple OH groups. All
the OH groups are functional groups and thus potential
reactive sites to form derivatives of the original
compound.” (Id. at ¶ 16). With respect to
“ultrasmall” term, Dr. Lewis relied on a
publication to define this term as a new class of contrast
agents “small enough to migrate across the capillary
wall, a prerequisite in the design of targetable particulate
pharmaceuticals.” (Id. at ¶ 19 (internal
support of Dr. Lewis' declaration, Applicant submits
multiple exhibits to the Patent Office. One of these
exhibits, Exhibit D, is entitled “European
Pharmacopoeia, 3rd Edition, 1997.” Exhibit D
states, “[s]terility is the absence of viable
micro-organisms […] [which] is assured by the
application of a suitably validated production
process.” As such, failure to follow a meticulously
validated process involves the risk of a non-sterile product
or of a deteriorated product. Wherever possible, “a
process in which the product is sterilized in its final
container (terminal sterilization) is chosen.” For
terminal sterilization, it is essential to take into account
the non-uniformity of the physical and chemical conditions
within the sterilizing chamber. By establishing a terminal
sterilization process, knowledge of its performance in
routine use is gained wherever possible, by monitoring and
suitably recording the physical and chemical conditions
achieved within the load in the chamber throughout each
attached Exhibits H and I, note that ultrasmall
superparamagnetic iron oxide (USPIO) are small enough to
migrate across the capillary wall, a prerequisite in the
design of targetable particulate pharmaceuticals. As such,
the applications of USPIO being-(i) used as an intravenous
contrast agent for the lymphatic system, (ii) a bone marrow
contrast agent, (iii) a long-half-life perfusion agent for
brain and heart, and (iv) the magnetic moiety in
organ-targeted superparamagnetic contrast agents for magnetic
resonance imaging. (Id. at Exhibit I,
Applicant's Arguments/Remarks filed June 4 2002,
October 8, 2002 and November 13, 2002.
respect to the remarks filed June 4, 2002, no significant
comments were made by the Applicant.
with respect to the remarks filed October 8, 2002, the
Applicant noted “[t]he change in claims such as 53 and
54 from ‘colloid' to ‘complex' is
intended to be a broadening amendment; similar language
already appeared in numerous claims.” (See
Applicant's Arguments/Remarks at 6, filed October 8,
2002). Additionally, Dr. Lewis' attached declaration
notes that the material in the patent application of the
'498 patent employs a synthetic method that “does
not require a reflux step or centrifugation. And the
resulting material falls apart upon autoclaving - i.e.,
heating at 121°C for 30 min. does not result in an
increase in particulate formulation.” (Decl. of Lewis
at ¶ 11, dated September 25, 2002). In addition, Dr.
Lewis notes that his experimental data indicates that such
“autoclaved materials are stable (as measured by no
increase in particulate level per mL of material) for up to 3
years.” (Id. at ¶ 12).
in the remarks filed November 13, 2002, Applicant again noted
that the changing of claim terms from “colloid”
to “complex” is intended to be a broadening
Notice of Allowance mailed on January 22, 2003.
the reasons for allowance, the Examiner noted that the
claimed subject matter was novel and nonobvious because the
prior art references did not disclose-(i) a reduced
carboxyalkylated polysaccharide iron oxide complex wherein
the complex is stable at a temperature of about 121°C;
and (ii) a method of providing an iron oxide complex for
administration to a mammalian subject consisting of producing
a carboxyalkylated reduced polysaccharide iron oxide complex
and sterilizing the complex by autoclaving. The Examiner
further noted that the declaration filed by Dr. Lewis on
October 8, 2002, was sufficient and persuasive to overcome
the prior art references because the material disclosed in
the prior art was “not stable upon autoclaving (heating
at 121 C for 30 minutes), ” unlike the material of the
patent application of the '498 patent.
The '479 Patent
Disclosure of the '479 Patent
Court notes that the patent application for the '479
patent is a continuation-in-part patent application for the
patent application for the '498 patent. As such, a
substantial portion of the disclosure in the '479 patent
is recited in the '498 patent. (See supra fn.
on a review of the disclosure of the '479 patent,
additional disclosure regarding the colloid particles is made
in the '479 patent. The '479 patent explains that
unlike the conventional drugs, Combidex® and
Feridex®, the colloid particles disclosed in
this patent application show less evidence of polysaccharide
dissociation under stress, and exhibiting no appreciable
change in size. The '479 patent identifies the
shortcomings with the conventional drugs such as loss of
dextran coating when subjected to heat stress, increase in
particle diameter size, and clumping of material.
(See the '479 patent, col. 11, ll. 5-20).
'479 patent discloses an improved method of
administration, which comprises injection of an autoclaved
reduced polysaccharide iron oxide complex in a volume of 15
mL or less. In another aspect of the embodiment the injected
volume is injected as a bolus. (See the '479
patent, col. 3, ll. 20-25).
'479 patent includes two (2) claims wherein claim 1 is in
independent form, and is directed to a pharmaceutical
composition in a vial. Claim 1 of the '479 patent, unlike
the claims of the '498 patent, recites carboxymethylated
dextran iron oxide complex, which comprises at least 750
micromole and less than 1500 micromole of carboxyl groups per
gram of dextran. (See the '479 patent, col. 38,
Prosecution History of the '479 Patent
Applicant's Arguments/Remarks filed December 14,
responding to the rejections set forth in the outstanding
Office action issued by the patent examiner, the Applicant
argued, “[w]hether a composition, or in this case a
complex, is terminally sterilizable - i.e. autoclavable -
depends on the chemical composition of the disclosed complex,
it does not describe a purpose or intended use.”
(See Applicant's Arguments/Remarks at 9, filed
December 14, 2006). The Applicant further states that
“[a]utoclavability is a physical property that reflects
a chemical property and thus chemical composition.”
(Id. at 10).
Applicant further notes that the term “terminally
sterilizable” also “adds patentable weight to the
claimed iron oxide composition, because not all reduced
carboxyalkylated polysaccharide iron oxide complexes are
terminally sterilizable and stable at temperatures of at
least 100°C.” As such, the term “terminally
sterilizable” imparts essential chemical structure via
this physical property because a composition that is
“terminally sterilizable” is chemically different
from one that is not. (Id. at 10). The Applicant
argued that they have developed “unexpectedly and
surprisingly” developed a process that prepares reduced
carboxyalkylated polysaccharide iron oxide complexes that can
be autoclaved without precipitating or degrading.
support of its arguments, the Applicant submitted a
declaration by one of the inventors', Dr. Jerome Lewis.
Generally, the declaration of Dr. Lewis submitted with the
Applicant's remarks was substantially similar to the
declaration by Dr. Lewis in the '498 patent.
Applicant's Arguments/Remarks filed February 23,
remarks, the Applicant addressed indefiniteness rejections
under 35 U.S.C. § 112, first paragraph by making certain
amendments. Next, the Applicant addressed obviousness
rejection by asserting that the cited art failed to disclose
“an injectable complex in a vial that is stable at a
temperature of about 100°C, or an injectable complex in a
vial that is terminally sterilizable (autoclavable) within
the vial.” (See Applicant's
Arguments/Remarks at 4, filed February 23, 2007).
Applicant's Arguments/Remarks filed May 4, 2007.
remarks, relying on the declaration by Dr. Lewis and Dr.
Timothy Frigo, the Applicant argued that unlike the
conventional drugs, PCU-USPIO iron oxide complex, showed an
insignificant change in size upon autoclaving. (See
Applicant's Arguments/Remarks at 5, filed May 4, 2007).
Dr. Timothy Frigo is an assignee of the '479 patent and
one of the senior scientists who prepared and analyzed the
substances disclosed in this patent. Dr. Frigo's
declaration indicates that the size of PCU-USPIO after
autoclaving did not change drastically, as it did for the
conventional drugs. (See Declaration of Dr. Frigo
(“Decl. of Frigo) at ¶¶ 10-11, filed May 4,
Notice of Allowance mailed on April 10, 2009.
reasons for allowance, the Examiner indicated that the
claimed subject matter is patentable over the cited art
because the compositions disclosed in the references are not
stable when subjected to autoclaving. As such, the
compositions in the claimed subject matter do “not form
into a gel or form substantial particulates and remains clear
and can be micro-filtered.” (See Notice of
Allowance at 3, mailed on April 10, 2009).
The '597 Patent
Disclosure of the '597 Patent
'597 patent is directed towards administrating an
effective amount of a pharmacological composition that uses
an iron oxide complex with a polyol or polyether. The complex
is formulated in a biocompatible liquid that provides minimal
detectable free iron in a subject and minimal incidence of
anaphylaxis (i.e., allergic reaction). (See the
'479 patent, col. 2, ll. 5-10). The '479 patent notes
that unlike the existing iron oxide complexes, polyol or
polyether iron oxide complexes disclosed herein, when
administered parenterally to a patient for use as a
pharmacological agent, provides minimal detectable free iron
and anaphylaxis in a patient. (Id. at col. 11, ll.
the improvement comprising that of parenteral administration
to a mammalian subject of an effective dose of the complex
formulated in a biocompatible liquid delivered at a rate
substantially greater than 1 mL/min. (Id. at col. 3,
ll. 40-45). The method of administration comprising-injection
of an autoclaved reduced polysaccharide iron oxide complex in
a volume of 15 mL or less. (Id. at col. 6, ll.
this patent notes that four of the conventional types of iron
oxide compounds used as MRI contrast agents and/or hematinic
agents (i.e., agents for increasing the amount of hemoglobin
in the blood) have serious drawbacks. (Id. at col.
15, ll. 45-65 and col. 16, ll. 1-25). Accordingly, the
embodiments of the '597 patent are directed to polyol or
polyether iron oxide complex, when administered to a patient,
provides both minimal detectable free iron in a subject and
minimal anaphylaxis in a patient. For example, as discussed
in examples 6 and 7 and examples 8 and 9 of the '597
patent. (Id. at col. 19, ll. 45-50). The polyol or
polyether iron oxide complex of the '597 patent are
administered parenterally by bolus injection at a dosage of
from about 1 mg to about 4 mg of iron/kg of body weight.
(Id. at col. 26, ll. 30-35).
'597 patent identifies autoclave or terminally sterilize
as synonyms. (Id. at col. 10, ll. 65-67).
“Terminal sterilization (autoclaving) is a preferred
method of sterilizing drugs for injection.”
(Id. at col. 13, ll. 4-5). “These colloids are
particularly suited to parenteral administration, because the
final sterilization typically is autoclaving, a preferred
method since it eliminates viability of all cellular life
forms including bacterial spores, and viruses.”
(Id. at col. 18, 35-40).
example 62, the '597 patent discloses that following
autoclaving for 30 minutes at 121°C, USPIO
coated with reduced dextran maintained its small size.
Whereas, USPIO coated with native dextran increased in size
28-fold following autoclaving. (Id. at col. 45, ll.
35-45). Additionally, a second type of increased stability
was achieved by use of reduced dextran to coat USPIO is the
property of pH of the bulk solvent. (Id. at col. 45,
ll. 50-55). The data in both Tables 12 and 13 show that the
particles coated with reduced dextran had significantly
improved pH stability upon autoclaving, compared to those
coated with native dextran. As such, the effect of
autoclaving on pH, size, and bound polysaccharide of colloids
coated with native and reduced dextran was observed.
(Id. at col. 45, ll. 55-col. 46, ll. 1-30).
example embodiment disclosed in the '597 patent is that
of a method that comprises mixing the polyol, reduced
polysaccharide, or polyether with iron salts in an acidic
solution selected from the group comprising ferric salts,
ferrous salts, or a mixture of ferrous and ferric salts,
cooling the solution, neutralizing the solution with a base,
and recovering the coated iron oxide colloid. (Id.
at col. 17, ll. 30-35). Cooling the solution to 5°C as
noted in example 5 or cooled to a room temperature as noted
in example 36. (Id. at col. 25, ll. 40-45; col. 37,
Prosecution History of the '597 Patent
Applicant's Arguments/Remarks filed July 3,
responding to the rejections set forth in the outstanding
Office action, the Applicant argued that the claimed subject
matter is directed to ‘pharmacological
compositions, ' which requires a composition that will be
acceptable for use in humans. That is, the aforementioned
term informs a person of ordinary skill in the art that the
iron oxide complex must have an acceptable profile with
respect to stability and risk of adverse reaction in humans.
(See Applicant's Arguments/Remarks at 7, filed
July 3, 2006). Applicant further goes onto indicate that
those skilled in the art recognize that in the art of
contrast agents, use of terminal sterilization (autoclaving)
over filter sterilization is preferred because terminal
sterilization provides a much higher level of sterility
assurance. (Id. at 7). As such, being desirable to
have polyol/polyether superparamagnetic iron oxide complex as
pharmacological composition that is capable of being
autoclaved and that can be administered after autoclaving to
provide minimal detectable free iron and minimal incidence of
anaphylaxis. (Id. at 8).
Applicant further identifies that the drug disclosed in the
patent application is better than the conventional drugs,
Combidex® and Feridex®, because
it has a sufficiently small risk of particulate formulation
after autoclaving that no filtration is required during
administration of the drug. Thereby, providing minimal free
iron to the subject upon administration. And, the risk of
adverse reaction is lower compared to the conventional drugs,
which results in more rapid administration of this new drug
without dilution. (Id. at 9).
the Applicant argues that the prior art cited did not
disclose a pharmacological composition that is
“capable of being parenterally administered
(composition), or actually administered (method), at
a rate substantially greater than 1mL/min.”
(Id. at 11). Further, the Applicant argues that the
reduced carboxyalkylated polysaccharide iron oxide complexes
claimed in the instant application can be autoclaved, and the
claims require that they be autoclaved or autoclavable.
(Id. at 14).
Applicant's Arguments/Remarks filed January 29,
support of its remarks, Applicant submitted a declaration of
Dr. Lewis, one of the inventors of this patent. In order to
distinguish over the cited art, the Applicant amended the
claims to include claim term “autoclavable” in
the body of the claim in order to give patentable weight to
this claim term. The Applicant asserted that
“[a]utoclavability is a physical property that reflects
a chemical property and thus limits the chemical
composition.” (See Applicant's
Arguments/Remarks at 8, filed January 29, 2007). And, because
not all reduced carboxyalkylated polysaccharide iron oxide
complexes are autoclaved and thus stable, the term
“autoclavable” adds patentable weight.
(Id. at 9). Dr. Lewis points out that that the
“distinguishing property of the complexes of the
present application compared to the previous generation
complexes Feridex and Combidex, and the [reference] Maruno EP
compound, is autoclavability.” (Id. at 10).
Applicant's Arguments/Remarks filed May 18,
support of its remarks, Applicant submitted a declaration of
Dr. Timothy Frigo, an assignee and one of the senior
scientists who prepares and analyzes the substances disclosed
in the this patent. Dr. Frigo noted that PSC-USPIO
proprietary iron oxide complex showed an insignificant change