DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement filed October 8, 2025 is acknowledged and has been considered by the examiner.
Drawings
The drawings are objected to because of the following informalities:
Figure 4C provides a line graph plotting two sets of data. However, in its current form, it is not possible to distinguish the T1 weighted SI and the T2 weighted SI, as these two sets of data are the same color and format with no distinguishing markings on this plot. Additionally, it is not clear what is meant by the “40mM 2h…” label on the x-axis of the plot.
Appropriate correction is required.
Specification
The use of terms which are trade names or marks used in commerce, has been noted in this application. The examiner notes the following instances of this occurrence:
On page 10 of the specification, there are recitations of MAGNEVIST®, MULTIHANCE®, EOVIST®, PRIMOVIST®, VASOVIST®, ABLAVAR®, OMNISCAN®, OPTIMARK®, DOTAREM®, and ARTIREM®.
On page 11 of the specification, there are recitations of PROHANCE®, GADOVIST®, GADAVIST®, ELUCIREM®, and VUEWAY®.
On pages 13-15 and 19 are recitations of PLURONIC® F-68.
On page 15 is a recitation of KRYTOX® and PLURONIC® F-127
In each instance, the terms should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 7 and 18 are objected to because of the following informalities:
Both of these claims contain the same list of components in the emulsion mixture. These appear to be a list of items separated by semicolons. However, there is a comma between the poloxamer nonionic surfactant component and the glyceride component. In view of the disclosure on the whole and claim 6, it appears that these are separate components in the emulsion composition. Thus, for consistency of list formatting, these components should be separated by a semicolon instead of a comma.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5-8, 13, and 17-19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 5, the phrase “such as” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of examination, the examiner will interpret the following phrase to not limit the claim. Furthermore, claim 6 is rejected due to its dependence on claim 5.
Regarding claim 5, the phrase “e.g.,” is interpreted by the examiner to have the same meaning as "for example," which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of examination, the examiner will interpret the following phrase to not limit the claim. Furthermore, claim 6 is rejected due to its dependence on claim 5.
Regarding claim 6, the phrase “such as” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of examination, the examiner will interpret the following phrase to not limit the claim.
Claim 7 recites the limitation “the gadolinium chelate” in the second line. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 7 depends, includes no recitation of a gadolinium chelate. For the purpose of examination, the examiner will interpret this limitation to read as “a gadolinium chelate” as is done in similarly structured claim 4.
Claim 7 recites the limitation “the poloxamer nonionic surfactant” in the third line. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 7 depends, includes no recitation of a poloxamer nonionic surfactant. For the purpose of examination, the examiner will interpret this limitation to read as “a poloxamer nonionic surfactant.”
Claim 7 recites the limitation “the final volume” in the fifth line. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 7 depends, includes no recitation of a final volume. For the purpose of examination, the examiner will interpret this limitation to read as “a final volume.”
Regarding claim 8, the phrase “e.g.,” is interpreted by the examiner to have the same meaning as "for example," which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of examination, the examiner will interpret the following phrase to not limit the claim.
Regarding claim 13, the phrase “such as” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of examination, the examiner will interpret the following phrase to not limit the claim.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 13 recites the broad recitation “at least 1.5T,” and the claim also recites “at least 3T” which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For the purpose of examination, the examiner will consider the scope of this limitation to be at least 1.5T.
Regarding claim 17, the phrase “such as” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of examination, the examiner will interpret the following phrase to not limit the claim.
Regarding claim 17, the phrase “e.g.,” is interpreted by the examiner to have the same meaning as "for example," which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of examination, the examiner will interpret the following phrase to not limit the claim.
Claim 18 recites the limitation “the poloxamer nonionic surfactant” in the third line. There is insufficient antecedent basis for this limitation in the claim. Claim 16, from which claim 18 depends, includes no recitation of a poloxamer nonionic surfactant. For the purpose of examination, the examiner will interpret this limitation to read as “a poloxamer nonionic surfactant.”
Regarding claim 19, the phrase “such as” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of examination, the examiner will interpret the following phrase to not limit the claim.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4-7 and 16-18 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 4, 7, and 16 require the emulsion composition to contain 5 to 20 mg/mL of a gadolinium chelate. However, claim 1, upon which claims 4 and 7 directly depend and upon which claim 16 indirectly depends (through claim 10), requires that the amount of the contrast agent in the composition be at least 10 mM. The examiner notes that not all gadolinium chelates at a concentration of 5 to 20 mg/mL meet the criteria of being at a concentration greater than or equal to 10 mM. To exemplify this point, the examiner provides the following examples:
Gd Chelate
MW (g/mol)
10mM =Xmg/mL
5mg/mL =XmM
20mg/mL =XmM
gadopentetate dimeglumine
938
9.38
5.33049
21.32196
gadobenate dimeglumine
1058
10.58
4.725898
18.90359
gadoxetate disodium
726
7.26
6.887052
27.54821
gadofosveset trisodium
958
9.58
5.219207
20.87683
gadodiamide
1071
10.71
4.668534
18.67414
gadoversetamide
662
6.62
7.55287
30.21148
gadoterate meglumine
753
7.53
6.640106
26.56042
gadoteridol
559
5.59
8.944544
35.77818
gadobutrol
605
6.05
8.264463
33.05785
gadopiclenol
970
9.7
5.154639
20.61856
The examiner notes that this is not a comprehensive list of gadolinium chelates within the scope of claims 4, 7, and 16 and other chelates may possess smaller or larger molecular weights, influencing this calculation. Importantly, it can be observed in the above table that for each exemplary Gd chelate a concentration of 5 mg/mL is not at a concentration of at least 10 mM. Therefore, claims 4, 7, and 16 include within their scopes embodiments that are not permitted in the claims upon which they depend. Thus, these claims fail to include all of the limitations of the claims upon which they depend. Furthermore, claims 5-6 and 17-18 depend on claims 4 and 16, respectively, and fail to resolve this deficiency, rendering these claims rejected as well.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Wolber (Wolber, J.; et al., Magn. Reson. Med., 1999).
Wolber teaches perfluorocarbon emulsions loaded with hyperpolarized xenon (pg. 442, Title and Abstract). More specifically, Wolber teaches emulsions of PFOB (perfluorooctyl bromide), lecithin surfactant loaded with laser-polarized xenon (Sample Preparation and Droplet Size Analysis, first two paragraphs). Wolber teaches that the xenon Ostwald solubility of PFOB was approximately 1.2 (pg. 443, left column, fourth paragraph). Wolber teaches performing MRI on rats after administering this emulsion (pg. 443, Animal Studies), teaching xenon as a contrast agent.
Wolber does not explicitly teach a contrast agent emulsion comprising at least 10 mM of a contrast agent in an emulsion comprising at least 10% w/v of a perfluorocarbon (as is required in claim 1) within a single embodiment. However, per Wolber does teach an emulsion composition of a perfluorocarbon and a contrast agent and changes in concentration generally do not support patentability (MPEP § 2144.05(II)), as changes in concentration of these components amounts to routine optimization. The skilled artisan would be motivated to optimize the amount of xenon and perfluorocarbon in the emulsion to optimize contrast signal and improve delivery of the contrast agent to the desired location. Therefore, the teachings of Wolber render claim 1 obvious.
Claims 1-2, 4-5, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Cacheris (US 5,614,170).
Cacheris teaches emulsions containing contrast agents (Abstract). More specifically, Cacheris teaches emulsions for use in MRI comprising an oil and/or a perfluorocarbon emulsified in an aqueous solution containing a metal chelate complex (column 2, lines 55-57). Cacheris teaches that a surfactant may also be included (column 2, lines 57-59). Cacheris teaches that the oil and/or perfluorocarbon may be present in amounts from about 0.5% to 50% by weight, specifically teaching a preferred range of 5-50% for the perfluorocarbon (column 2, line 60; through column 3, line 4). Cacheris teaches that a surfactant may be present in amounts from about 05% to 10% by weight and that the MRI agent may be dispersed in amounts up to 30% by weight (column 3, lines 6-9). Cacheris teaches that specific examples of the MRI agent chelate complex includes gadolinium diethylenetriaminepentaacetic acid bis(N-stearyl-N-hydroxylamide), gadolinium diethylenetriaminepentaacetic acid bis(N-tetradecyl-N-hydroxylamide), and gadolinium diethylenetriaminepentaacetic acid bis(N-hexadecyl-N-hydroxylamide) (column 3, lines 50-56). Cacheris teaches that the oil may be selected from a range of physiologically acceptable substances including mineral, vegetable, animal, essential, or synthetic oils; including seed oils, fish oils, and corn oils (column 3, line 57; through column 4, line 15). Furthermore, Cacheris teaches that the perfluorocarbon chemical can be perfluorodecalin (column 4, lines 30-35). Additionally, Cacheris teaches that the identity of the surfactant used in such a composition can vary and can include Pluronic® poloxamers and cholesterol derivatives (column 5, lines 13-28). Cacheris teaches an example containing 2% lecithin, 10% safflower oil, and 5% GdDTPA-bis(N-stearyl-N-hydroxylamide) (column 6, lines 31-34; and Table 9) and describes lecithin as a surfactant (column 11, line 26).
Cacheris does not explicitly teach a contrast agent emulsion comprising at least 10 mM of a contrast agent in an emulsion comprising at least 10% w/v of a perfluorocarbon within a single embodiment. However, Cacheris teaches that the emulsion can be composed of a range of components in a range of amounts. Thus, it would have been prima facie obvious before the effective filing date of the claimed invention to combine these features, as a skilled artisan would recognize that these elements were known in the art.
Regarding claim 1, Cacheris teaches an emulsion containing 2% lecithin, 10% safflower oil, and 5% GdDTPA-bis(N-stearyl-N-hydroxylamide) (column 6, lines 31-34; and Table 9). Cacheris teaches that the oil phase in such emulsions can be replaced with perfluorocarbons, which may be present in similar amounts (column 2, line 55 through column 3, line 3). The substitution of a perfluorocarbon for the safflower oil in the example of Cacheris would result in an emulsion composition comprising 10% of a perfluorocarbon by weight. While this does not directly read on the limitation of at least 10% w/v of a perfluorocarbon, changes in concentration generally do not support patentability (MPEP § 2144.05(II)), as changes in the concentration of perfluorocarbon may amount to routine optimization. Indeed, Cacheris teaches that altering oil/perfluorocarbon phase concentration impacts the viscosity of the composition, which should be optimized to the means of administration. Thus, the skilled artisan would be motivated to optimize the amount of perfluorocarbon in the composition. Similarly, while Cacheris does not directly teach a 10 mM concentration of the contrast agent, this similarly amounts to a change in concentration rendered obvious by routine optimization (MPEP § 2144.05(II)), as the skilled artisan would be motivated to adjust the amount of contrast agent (gadolinium chelate) in the composition to improve signal to noise in MRI usage. Therefore, the teachings of Cacheris render claim 1 obvious.
Regarding claim 2, the above-described example of Cacheris teaches a GdDTPA-bis(N-stearyl-N-hydroxylamide) contrast agent (Table 9). The examiner interprets this to be a gadolinium chelate contrast agent. Cacheris further teaches that the MRI agent can be various metal chelates of gadolinium (column 3, lines 51-56). Therefore, the teachings of Cacheris render claim 2 obvious.
Regarding claim 4, the above described example of Cacheris teaches an emulsion containing 2% lecithin, 10% safflower oil, and 5% GdDTPA-bis(N-stearyl-N-hydroxylamide) (column 6, lines 31-34; and Table 9) and renders obvious a composition wherein 10% of perfluorocarbon is present instead of the safflower oil (column 2, line 55 through column 3, line 3). Cacheris teaches that lecithin is a surfactant (column 11, line 26). As described above, GdDTPA-bis(N-stearyl-N-hydroxylamide) is interpreted to be a gadolinium chelate. Furthermore, lecithin is an emulsifier, surfactant and/or other lipid. Cacheris teaches that these emulsions are prepared in water (column 2, line 56). Thus, the examiner interprets there to be an aqueous phase to a final volume of the composition. Regarding the concentrations of the gadolinium chelate, perfluorocarbon, and emulsifier, while the example of Cacheris does not explicitly teach these concentrations, these concentrations are rendered obvious because changes in concentration generally amount to routine optimization (MPEP § 2144.05(II)). The skilled artisan would be motivated to optimize the viscosity, emulsion particle size, and contrast signal of the composition to improve performance of the product in MRI usage. Therefore, the teachings of Cacheris render claim 4 obvious.
Regarding claim 5, the above-described example of Cacheris contains lecithin, which Cacheris describes as a surfactant (column 6, lines 31-34; Table 9; and column 11, line 26). Therefore, the teachings of Cacheris render claim 5 obvious.
Regarding claim 8, Cacheris teaches that such emulsions containing gadolinium chelates and perfluorocarbons can contain perfluorodecalin (column 4, lines 30-35). Therefore, the teachings of Cacheris render claim 8 obvious.
Claims 10, 12-14, 16, 17, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Temme (Temme, S.; et al., Circulation, 2015) in view of Cacheris.
Temme teaches a method of performing magnetic resonance imaging of venous thrombosis using a perfluorocarbon emulsion composition (pg. 1405, Title and Abstract). Temme teaches using emulsions of a perfluorocarbon surrounded with a lecithin layer (pg. 1407, Figure 1A). Temme teaches injecting the emulsion into the tail vein of mice and then performing MRI (pg. 1407, left column, first paragraph). Temme teaches performing MRI using a 9.4T MRI scanner (pg. 1407, MRI Studies). Temme teaches obtaining magnetic resonance imaging images of venous thrombosis in the mice (pg. 1407, Figure 1B; and pg. 1409, Figure 3B).
Temme does not teach a method of performing magnetic resonance imaging using the emulsion composition of claim 1.
As described above, Cacheris teaches emulsions for use in MRI comprising an oil and/or a perfluorocarbon emulsified in an aqueous solution containing a metal chelate complex (column 2, lines 55-57). Cacheris teaches that a surfactant may also be included (column 2, lines 57-59). Cacheris teaches that the oil and/or perfluorocarbon may be present in amounts from about 0.5% to 50% by weight, specifically teaching a preferred range of 5-50% for the perfluorocarbon (column 2, line 60; through column 3, line 4). Cacheris teaches that a surfactant may be present in amounts from about 05% to 10% by weight and that the MRI agent may be dispersed in amounts up to 30% by weight (column 3, lines 6-9). Cacheris teaches that specific examples of the MRI agent chelate complex includes gadolinium diethylenetriaminepentaacetic acid bis(N-stearyl-N-hydroxylamide), gadolinium diethylenetriaminepentaacetic acid bis(N-tetradecyl-N-hydroxylamide), and gadolinium diethylenetriaminepentaacetic acid bis(N-hexadecyl-N-hydroxylamide) (column 3, lines 50-56). Cacheris teaches that the oil may be selected from a range of physiologically acceptable substances including mineral, vegetable, animal, essential, or synthetic oils; including seed oils, fish oils, and corn oils (column 3, line 57; through column 4, line 15). Furthermore, Cacheris teaches that the perfluorocarbon chemical can be perfluorodecalin (column 4, lines 30-35). Additionally, Cacheris teaches that the identity of the surfactant used in such a composition can vary and can include Pluronic® poloxamers and cholesterol derivatives (column 5, lines 13-28). Cacheris teaches an example containing 2% lecithin, 10% safflower oil, and 5% GdDTPA-bis(N-stearyl-N-hydroxylamide) (column 6, lines 31-34; and Table 9) and describes lecithin as a surfactant (column 11, line 26). As described above, the teachings of Cacheris render claim 1 obvious.
A person of ordinary skill in the art would recognize that both Temme and Cacheris teach using perfluorocarbon emulsions for MRI imaging. It would also be recognized that both perfluorocarbon emulsions use lecithin as the surfactant.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Temme by substituting the perfluorocarbon emulsion used by Temme with the perfluorocarbon emulsion composition of Cacheris because these emulsions serve the same purpose of generating contrast for magnetic resonance imaging (MPEP § 2143(I)(B)). This substitution would predictably result in a method of imaging an organ having a cavity comprising administering an emulsion of claim 1 into a cavity of the organ and obtaining an MRI image of the organ having a cavity containing the emulsion.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this substitution because these emulsions are similar in structure, having a lecithin surfactant outer layer and a perfluorocarbon core. Thus, they would be expected to share relevant properties for use in MRI.
The skilled artisan would have been motivated to make this substitution because the emulsion of Cacheris also contains gadolinium, which imparts additional utility in performing MRI imaging.
Regarding claim 10, as described above, the teachings of Cacheris render the emulsion composition of claim 1 obvious. Additionally, Temme teaches a method of imaging an organ having a cavity of a patient comprising administering a perfluorocarbon emulsion into a cavity of the organ having a cavity (pg. 1407, left column, first paragraph) and obtaining a magnetic resonance imaging image of the organ having a cavity containing the perfluorocarbon emulsion composition (Figure 1B and Figure 3B). As Temme teaches imaging venous thrombi (Figure 3 caption), the examiner considers the blood vessel to be the organ having a cavity. Indeed, Applicant states in [0052] that organs having a cavity include blood vessels. Furthermore, as Temme teaches administration of the perfluorocarbon emulsion into the tail vein of the mice (pg. 1407, left column, first paragraph), the examiner interprets this as administering the emulsion into the cavity of the organ with a cavity being imaged. Therefore, the combined teachings of Temme and Cacheris render claim 10 obvious.
Regarding claim 12, Temme teaches imaging venous thrombi (Figure 3). The examiner interprets this to mean that Temme is imaging blood vessels. Therefore, the combined teachings of Temme and Cacheris render claim 12 obvious.
Regarding claim 13, Temme teaches using a 9.4T MRI scanner (pg. 1407, MRI Studies). Therefore, the combined teachings of Temme and Cacheris render claim 13 obvious.
Regarding claim 14, Cacheris teaches a perfluorocarbon emulsion containing a GdDTPA-bis(N-stearyl-N-hydroxylamide) contrast agent (Table 9). The examiner interprets this to be a gadolinium chelate contrast agent. Cacheris further teaches that the MRI agent can be various metal chelates of gadolinium (column 3, lines 51-56). Therefore, the combined teachings of Temme and Cacheris render claim 14 obvious.
Regarding claim 16, the above described example of Cacheris teaches an emulsion containing 2% lecithin, 10% safflower oil, and 5% GdDTPA-bis(N-stearyl-N-hydroxylamide) (column 6, lines 31-34; and Table 9) and renders obvious a composition wherein 10% of perfluorocarbon is present instead of the safflower oil (column 2, line 55 through column 3, line 3). Cacheris teaches that lecithin is a surfactant (column 11, line 26). As described above, GdDTPA-bis(N-stearyl-N-hydroxylamide) is interpreted to be a gadolinium chelate. Furthermore, lecithin is an emulsifier, surfactant and/or other lipid. Cacheris teaches that these emulsions are prepared in water (column 2, line 56). Thus, the examiner interprets there to be an aqueous phase to a final volume of the composition. Regarding the concentrations of the gadolinium chelate, perfluorocarbon, and emulsifier, while the example of Cacheris does not explicitly teach these concentrations, these concentrations are rendered obvious because changes in concentration generally amount to routine optimization (MPEP § 2144.05(II)). The skilled artisan would be motivated to optimize the viscosity, emulsion particle size, and contrast signal of the composition to improve performance of the product in MRI usage. Therefore, the combined teachings of Temme and Cacheris render claim 16 obvious.
Regarding claim 17, the above-described example of Cacheris contains lecithin, which Cacheris describes as a surfactant (column 6, lines 31-34; Table 9; and column 11, line 26). Additionally, the perfluorocarbon emulsion of Temme contains the lecithin surfactant (Figure 1). Therefore, the combined teachings of Temme and Cacheris render claim 17 obvious.
Regarding claim 19, Cacheris teaches that such emulsions containing gadolinium chelates and perfluorocarbons can contain perfluorodecalin (column 4, lines 30-35). Therefore, the combined teachings of Temme and Cacheris render claim 19 obvious.
Claims 1-5, 8, 10-11, 13-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Tyagi (Tyagi, P.; et al., Am. J. Physio. Renal Physiol., 2017 – provided by applicant in IDS filed October 8, 2025) in view of Yokoyama (US 4,252,827) as evidenced by Mattrey (Mattrey, R. F.; et al., Am. J. Roentgenol., 1987), Unger (US 5,368,840), and Palacios (Palacios, L. E.; et al., J. Am. Oil Chem. Soc., 2005).
Tyagi teaches the use of a contrast mixture composition for the imaging of bladder injury (pg. 1, Title and Abstract). Specifically, Tyagi teaches administration of a mixture of 5 mM ferumoxytol and 0.4-64 mM Gd-DTPA or gadobutrol directly into the lumen of the bladder of rats via catheter (pg. 1-2, Animals). Tyagi teaches then performing MRI with a 7-Tesla instrument and acquiring MRI images (pg. 2, Instruments; and Figure 2). Tyagi teaches that this MRI technique achieves increased contrast of the bladder wall due to the effect of the iron oxide particles in the bladder lumen quenching the signal from the gadolinium chelate (pg. 6, left column, first paragraph).
Tyagi does not teach an emulsion composition comprising a gadolinium chelate and a perfluorocarbon nor the use of such a composition for MRI imaging.
Yokoyama teaches perfluorocarbon emulsion compositions (Abstract). The emulsion of Yokoyama comprises at least one perfluorocarbon compound from the group consisting of perfluorodecalin, perfluoromethyldecalin, perfluoro alkylcyclohexanes, perfluoro alkyltetrahydrofurans, perfluoroalkanes (column 2, line 64 through column 3, line 3). The emulsion of Yokoyama also comprises a second perfluorocarbon compound (column 3, lines 3-9). The total amount of the perfluorocarbon in the emulsion is about 10 to about 50% w/v (column 3, lines 59-60). The emulsion of Yokoyama also contains 2-5% w/v nonionic surfactant (column 3, lines 17-23) and phospholipid emulsifiers including either yolk or soybean phospholipids at 0.1-1% w/v (column 3, lines 61-66). Yokoyama also teaches that the emulsion contains fatty acid compounds, which may be caprylic acid, capric acid, oleic acid at an amount of 0.004-0.1% w/v (column 3, line 67 to column 4, line 16). Yokoyama teaches that the emulsion is prepared in an aqueous medium, such as water (column 4, lines 16-24). Yokoyama teaches an example embodiment in Table 4 comprising 25.3% w/v perfluorodecalin, 0.6% w/v yolk phospholipid, and 3.4% PLURONIC® F68 (which Yokoyama describes as a polyoxyethylene-polyoxypropylene copolymer).
Mattrey teaches the use of perfluorochemicals as MRI contrast agents for gastrointestinal imaging (pg. 1259, Title and Abstract). Mattrey teaches that perfluorochemical compounds have potential as magnetic resonance contrast agents due to a lack of hydrogen, creating a signal void in both T1 and T2 weighted images, darkening the organ lumen (pg. 1263, left column, first paragraph).
Unger teaches MRI contrast compositions comprising polymers in combination with various contrast agents (Abstract). Unger provides a description of various MRI contrast agents understood in the art, describing that gadolinium chelates are considered positive contrast agents and teaching that both iron oxide particles and perfluorocarbon materials are considered negative contrast agents as they both decrease signal in tissue lumen (column 2, lines 11-56).
Palacios teaches fractionation of lipids from egg yolks (pg. 571, Title and Abstract). Palacios describes the collection of phospholipids from egg yolks as lecithin (Introduction). Palacios teaches that egg yolk lecithin is used as an emulsifier in pharmaceutical and cosmetic compositions (pg. 571, Introduction, first paragraph, lines 9-10).
As evidenced by Palacios, a person of ordinary skill in the art would interpret the egg yolk phospholipids of Yokoyama to be lecithin. Additionally, it would be recognized that both Mattrey and Unger teach that perfluorocarbon materials can be used to decrease the signal in the lumen of organs in MRI imaging and that Unger describes perfluorocarbons as similar to iron oxide particles in this way. Thus, it would be recognized that perfluorocarbons materials and iron oxide particles such as ferumoxytol perform the same function in MRI.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the contrast composition and method of bladder MRI of Tyagi by substituting the ferumoxytol iron particles with the perfluorocarbon emulsion of Yokoyama because these materials serve the same purpose in MRI imaging, as evidenced by Mattrey and Unger (MPEP § 2143(I)(B)). This combination would predictably have yielded a contrast emulsion composition comprising a gadolinium chelate and a perfluorocarbon and a method of performing MRI of the cavity of an organ using said composition.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this substitution because Yokoyama teaches the perfluorocarbon emulsion is suitable for administration to living subjects. Yokoyama also teaches preparation of the emulsion in an aqueous medium and Tyagi teaches preparing the gadolinium chelate in saline. Thus, the emulsion of Yokoyama could be prepared using the aqueous gadolinium chelate solution as the aqueous phase.
The skilled artisan would have been motivated to make this substitution because Mattrey teaches that perfluorocarbons are effective magnetic resonance contrast agents and teaches that such agents are safe and have no side effects (pg. 1259, second paragraph, last sentence).
Regarding claim 1, Tyagi teaches a contrast agent mixture of 0.4-64 mM Gd-DTPA or gadobutrol in combination with a negative contrast agent (pg. 2, left column, first paragraph). Additionally, Yokoyama teaches an emulsion composition comprising 10-50% w/v perfluorocarbon materials (column 3, lines 59-60). As described above, it would have been obvious to prepare the emulsion in combination with the gadolinium chelates of Tyagi. This product would thus contain 0.4-64 mM gadolinium chelate and 10-50% w/v perfluorocarbon. As both of these ranges overlap the claimed ranges, these teachings render these limitations obvious (MPEP § 2144.05(I)). Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 1 obvious.
Regarding claim 2, Tyagi teaches a contrast agent mixture of 0.4-64 mM Gd-DTPA or gadobutrol in combination with a negative contrast agent (pg. 2, left column, first paragraph). The examiner interprets these to be gadolinium chelate contrast agents. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 2 obvious.
Regarding claim 3, Tyagi teaches a contrast agent mixture may contain gadobutrol in combination with a negative contrast agent (pg. 2, left column, first paragraph). Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 3 obvious.
Regarding claim 4, Tyagi teaches a contrast agent mixture containing 0.4-64 mM Gd-DTPA in combination with a negative contrast agent (pg. 2, left column, first paragraph). As the molecular weight of this complex is 547.57 g/mol, this range is equivalent to 0.22-35 mg/mL in concentration of gadolinium chelate. Additionally, Yokoyama teaches an emulsion composition comprising 10-50% w/v perfluorocarbon materials (column 3, lines 59-60). Furthermore, Yokoyama teaches the emulsion contains 2-5% w/v of a nonionic surfactant (column 3, lines 17-23). Each of these ranges overlaps with the claimed ranges, rendering them obvious (MPEP § 2144.05(I)). Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 4 obvious.
Regarding claim 5, Yokoyama teaches that the surfactant may be a polyoxyethylene-polyoxypropylene copolymer (column 3, lines 17-23), which the examiner interprets to be a poloxamer. Furthermore, Yokoyama teaches an example in which this copolymer is PLURONIC® F68, which is the trade name of a poloxamer. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 5 obvious.
Regarding claim 8, Yokoyama teaches an example wherein the emulsion comprises 25.3% w/v perfluorodecalin (Table 4). Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 8 obvious.
Regarding claim 10, Tyagi teaches a method of imaging the bladder in a rat using a composition comprising Gd-DTPA or gadobutrol gadolinium chelate in combination with a negative contrast agent using MRI (pg. 2, left column, first and second paragraphs; and Figure 2). Yokoyama teaches perfluorocarbon emulsions containing 10-50% w/v perfluorocarbon materials (column 3, lines 59-60). As described above, it would have been obvious to substitute the iron particles of Tyagi with the perfluorocarbon emulsion of Yokoyama, including the gadolinium chelate in the emulsion composition. Furthermore, Tyagi teaches administering the contrast mixture by catheter directly into the lumen of the bladder (pg. 1-2, Animals). The examiner interprets this to be a method in which the composition is administered into the cavity of the organ and MRI imaging is acquired of the organ with that cavity. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 10 obvious.
Regarding claim 11, Tyagi teaches a method of imaging the bladder of rats using a contrast mixture (pg. 1, Animals; and Figure 2). Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 11 obvious.
Regarding claim 13, Tyagi teaches using a 7-Tesla MRI scanner (pg. 2, Instruments). Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 13 obvious.
Regarding claim 14, Tyagi teaches a contrast agent mixture of 0.4-64 mM Gd-DTPA or gadobutrol in combination with a negative contrast agent (pg. 2, left column, first paragraph). The examiner interprets these to be gadolinium chelate contrast agents. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 14 obvious.
Regarding claim 15, Tyagi teaches a contrast agent mixture may contain gadobutrol in combination with a negative contrast agent (pg. 2, left column, first paragraph). Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 15 obvious.
Regarding claim 16, Tyagi teaches a contrast agent mixture containing 0.4-64 mM Gd-DTPA in combination with a negative contrast agent (pg. 2, left column, first paragraph). As the molecular weight of this complex is 547.57 g/mol, this range is equivalent to 0.22-35 mg/mL in concentration of gadolinium chelate. Additionally, Yokoyama teaches an emulsion composition comprising 10-50% w/v perfluorocarbon materials (column 3, lines 59-60). Furthermore, Yokoyama teaches the emulsion contains 2-5% w/v of a nonionic surfactant (column 3, lines 17-23). Each of these ranges overlaps with the claimed ranges, rendering them obvious (MPEP § 2144.05(I)). Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 16 obvious.
Regarding claim 17, Yokoyama teaches that the surfactant may be a polyoxyethylene-polyoxypropylene copolymer (column 3, lines 17-23), which the examiner interprets to be a poloxamer. Furthermore, Yokoyama teaches an example in which this copolymer is PLURONIC® F68, which is the trade name of a poloxamer. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 17 obvious.
Regarding claim 19, Yokoyama teaches an example wherein the emulsion comprises 25.3% w/v perfluorodecalin (Table 4). Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 19 obvious.
Regarding claim 20, Tyagi teaches a method of imaging the bladder in a rat using a composition comprising Gd-DTPA or gadobutrol gadolinium chelate in combination with a negative contrast agent using MRI (pg. 2, left column, first and second paragraphs; and Figure 2). Yokoyama teaches perfluorocarbon emulsions containing 10-50% w/v perfluorocarbon materials (column 3, lines 59-60). As described above, it would have been obvious to substitute the iron particles of Tyagi with the perfluorocarbon emulsion of Yokoyama, including the gadolinium chelate in the emulsion composition. Furthermore, Tyagi teaches administering the contrast mixture by catheter directly into the lumen of the bladder (pg. 1-2, Animals). The examiner interprets this to be a method in which the composition is administered into the cavity of the organ and MRI imaging is acquired of the organ with that cavity. As the claim language regarding the composition used is that the composition administered “comprises at least 10% w/v of a perfluorocarbon,” a combination composition further containing a gadolinium chelate reads on this claimed composition as the comprising language allows for the presence of additional components. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render claim 20 obvious.
Claims 6-7, 9, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Tyagi and Yokoyama, as evidenced by Mattrey, Unger, and Palacios, as applied to claims 1-5, 8, 10-11, 13-17, and 19-20 above, and further in view of Fernandez-Tarrio (Fernandez-Tarrio, M.; et al., AAPS PharmSciTech, 2008).
As described above, the combined teachings of Tyagi and Yokoyama render obvious the emulsion composition of claim 1 and its use for MRI imaging of an organ with a cavity. In summary, Tyagi teaches the use of a contrast mixture composition of 5 mM ferumoxytol (a negative contrast agent) and 0.4-64 mM Gd-DTPA or gadobutrol for the imaging of bladder injury (pg. 1-2, Animals). Yokoyama teaches perfluorocarbon emulsion compositions comprising about 10 to about 50% w/v perfluorocarbon, (column 3, lines 59-60), 2-5% w/v nonionic surfactant (which may be a poloxamer) (column 3, lines 17-23), and 0.1-1% w/v yolk or soybean phospholipids (column 3, lines 61-66). Yokoyama also teaches that the emulsion contains fatty acid compounds, which may be caprylic acid, capric acid, oleic acid at an amount of 0.004-0.1% w/v (column 3, line 67 to column 4, line 16). Yokoyama teaches an example embodiment in Table 4 comprising 25.3% w/v perfluorodecalin, 0.6% w/v yolk phospholipid, 3.4% PLURONIC® F68 (which Yokoyama describes as a polyoxyethylene-polyoxypropylene copolymer), and 0.004% w/v potassium oleate fatty acid. As evidenced by Palacios, yolk phospholipids are lecithin. Additionally, as evidenced by Mattrey and Unger, a skilled artisan would recognize the perfluorocarbon emulsion of Yokoyama as a negative MRI contrast agent that would suppress MRI signal, similar to the mechanism of the ferumoxytol of Tyagi.
The combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios does not teach an emulsion composition (or the use thereof) wherein the emulsion composition comprises capryl caproyl polyoxyl-8 glycerides and/or oleoyl polyoxyl-6 glycerides.
Fernandez-Tarrio teaches pharmaceutical emulsions of griseofulin (pg. 471, Title and Abstract). More specifically, Fernandez-Tarrio teaches the optimization of surfactants and co-surfactants (copolymers and glycerides) in the preparation of emulsions (pg. 473, Copolymer/Glyceride systems). Fernandez-Tarrio teaches that the combination of LABRASOL® with PLURONIC® F127 at different weight percents prepared good emulsions (Table II). Fernandez-Tarrio teaches that the LABRASOL®/PF127 mixture was a stable emulsion (pg. 478, left column, first paragraph, last sentence). Fernandez-Tarrio teaches that LABRASOL® is saturated polyglycolysed (PEG-8) caprylic/capric glycerides (pg. 472, Materials).
A person of ordinary skill in the art would recognize that both the product of the combination of the teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios and Fernandez-Tarrio relate to pharmaceutical emulsion compositions. It would also be recognized that both emulsion systems include poloxamers. It would further be recognized that Fernandez-Tarrio specifically teaches that poloxamers and polyglycolyzed glycerides result in highly stable emulsions when used in combination. It would also be recognized that Yokoyama teaches including fatty acid and glycerides thereof in such emulsions.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the contrast composition and method of bladder MRI of the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios by adding the caprylic/capric glyceride (LABRASOL®) of Fernandez-Tarrio to the emulsion composition because Fernandez-Tarrio teaches that this glyceride improves the stability of a poloxamer emulsion, which is a similar emulsion to that of Yokoyama (and the combination of references described above) that can be improved in the same way (MPEP § 2143(I)(C)). This combination would predictably have yielded a contrast emulsion composition comprising a gadolinium chelate, a perfluorocarbon, lecithin, a poloxamer, and a transesterified ethoxylated oil and a method of performing MRI of the cavity of an organ using said composition.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this substitution because both Yokoyama and Fernandez-Tarrio teach pharmaceutical emulsion compositions suitable for administration to living subjects. Additionally, Yokoyama teaches that the perfluorocarbon emulsion may contain fatty acids or glycerides thereof.
The skilled artisan would have been motivated to make this modification because Fernandez-Tarrio teaches that the combination of a poloxamer and LABRASOL® resulted in emulsions with increased stability.
Regarding claim 6, as described above, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render obvious the emulsion composition of claims 1, 4, and 5, producing an emulsion composition comprising 0.4-64 mM gadolinium chelate, 10-50% w/v perfluorocarbon, and 2-5% w/v of a poloxamer surfactant. Additionally, Fernandez-Tarrio teaches adding LABRASOL® (polyglycolysed (PEG-8) caprylic/capric glycerides) to poloxamer-containing emulsions (Table II). The examiner notes that in paragraph [0060] of the instant specification, Applicant states that transesterified ethoxylated vegetable oils include capryl caproyl polyoxyl-8 glycerides, e.g., LABRASOL®. Therefore, the examiner interprets the LABRASOL® of Fernandez-Tarrio to read on the limitation of claim 6. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, Palacios, and Fernandez-Tarrio render claim 6 obvious.
Regarding claim 7, Tyagi teaches a contrast agent mixture containing 0.4-64 mM Gd-DTPA in combination with a negative contrast agent (pg. 2, left column, first paragraph). As the molecular weight of this complex is 547.57 g/mol, this range is equivalent to 0.22-35 mg/mL in concentration of gadolinium chelate. Additionally, Yokoyama teaches an emulsion composition comprising 10-50% w/v perfluorocarbon materials (column 3, lines 59-60). Furthermore, Yokoyama teaches the emulsion contains 2-5% w/v of a nonionic surfactant, preferably a poloxamer (column 3, lines 17-23) and 0.1-1% w/v yolk phospholipid (column 3, lines 61-66). As evidenced by Palacios, egg yolk phospholipids can alternatively be described by the term lecithin (pg. 571, Introduction). Each of these ranges overlaps with the claimed ranges, rendering them obvious (MPEP § 2144.05(I)). Additionally, Fernandez-Tarrio teaches preparing emulsions with a combination of a LABRASOL® and a poloxamer at 80:20 and 60:40 w/w ratios (Table II). Applying these ratios to the range of Yokoyama would yield LABRASOL® amount ranges of 8-20% w/v and 3-7.5% w/v, respectively. The examiner notes that the range of 3-7.5% w/v approaches that of the claimed 1.5-2% w/v ethoxylated oil (MPEP § 2144.05(I)). Furthermore, the examiner notes that the difference between the taught composition and the claimed composition is a matter of the concentration of ethoxylated oil present in the emulsion. Per MPEP § 2144.05(II)(A), generally, differences in concentration do not support patentability unless there is evidence indicating such concentration is critical. Adjustment of surfactant, fatty acid, and glyceride concentrations in an emulsion amounts to routine optimization, as the skilled artisan would be motivated to optimize the particular concentrations of each component for any emulsion prepared (similar to how Fernandez-Tarrio teaches optimizing the ratio between poloxamer and ethoxylated oil) to optimize emulsion stability and particle size. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, Palacios, and Fernandez-Tarrio render claim 7 obvious.
Regarding claim 9, Yokoyama teaches perfluorocarbon emulsion compositions that may comprise perfluorodecalin (column 3, lines 27-56), poloxamer surfactant (column 3, lines 17-23), and yolk or soybean phospholipid (column 3, lines 61-66). Yokoyama teaches a specific embodiment containing perfluorodecalin, yolk phospholipid, and PLURONIC® F68 poloxamer (Table 4). As evidenced by Palacios, egg yolk phospholipids can alternatively be described by the term lecithin (pg. 571, Introduction). Additionally, Fernandez-Tarrio teaches adding LABRASOL® (polyglycolysed (PEG-8) caprylic/capric glycerides) to poloxamer-containing emulsions (Table II). The examiner notes that in paragraph [0060] of the instant specification, Applicant states that transesterified ethoxylated vegetable oils include capryl caproyl polyoxyl-8 glycerides, e.g., LABRASOL®. Therefore, the examiner interprets the LABRASOL® of Fernandez-Tarrio to read on the limitation of claim 9. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, Palacios, and Fernandez-Tarrio render claim 9 obvious.
Regarding claim 18, as described above, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, and Palacios render the method of claim 16 obvious. As described above, the incorporation of the cosurfactant LABRASOL® of Fernandez-Tarrio in the emulsion composition and method of use thereof of Tyagi, Yokoyama, Mattrey, Unger, and Palacios would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention. Additionally, as described in the rejection to claim 7, this would result in a composition containing 0.4-64 mM Gd-DTPA, 10-50% w/v perfluorocarbon, and 2-5% w/v poloxamer nonionic surfactant, and 0.1-1.0% w/v lecithin. As demonstrated above, 0.4-64 mM Gd-DTPA is equivalent to the range of 0.22-35 mg/mL gadolinium chelate. Each of these ranges overlaps with the claimed ranges, rendering them obvious (MPEP § 2144.05(I)). Additionally, Fernandez-Tarrio teaches preparing emulsions with a combination of a LABRASOL® and a poloxamer at 80:20 and 60:40 w/w ratios (Table II). Applying these ratios to the range of Yokoyama would yield LABRASOL® amount ranges of 8-20% w/v and 3-7.5% w/v, respectively. The examiner notes that the range of 3-7.5% w/v approaches that of the claimed 1.5-2% w/v ethoxylated oil (MPEP § 2144.05(I)). Furthermore, the examiner notes that the difference between the taught composition and the claimed composition is a matter of the concentration of ethoxylated oil present in the emulsion. Per MPEP § 2144.05(II)(A), generally, differences in concentration do not support patentability unless there is evidence indicating such concentration is critical. Adjustment of surfactant, fatty acid, and glyceride concentrations in an emulsion amounts to routine optimization, as the skilled artisan would be motivated to optimize the particular concentrations of each component for any emulsion prepared (similar to how Fernandez-Tarrio teaches optimizing the ratio between poloxamer and ethoxylated oil) to optimize stability and size of the emulsion product. Therefore, the combined teachings of Tyagi, Yokoyama, Mattrey, Unger, Palacios, and Fernandez-Tarrio render claim 18 obvious.
Pertinent art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
As pertinent art, the examiner cites Mattrey 1989 (Mattrey, R. F., Am. J. Roentgenol., 1989). Mattrey provides a review of perfluorochemical compounds as contrast agents, providing a status of that which was known to skilled artisans in biomedical imaging in 1989. Mattrey 1989 provides a summary of the use of perfluorocarbon compositions for imaging using computed tomography (pg. 248), sonography (pg. 249), and magnetic resonance imaging (pg. 249-251). Mattrey 1989 teaches that perfluorocarbons are useful for MRI because they darken lumen of organs, are immiscible with water, and are safe to use (pg. 249-250, PFOB as an Oral MR Contrast Agent). Mattrey 1989 also teaches that perfluorocarbon emulsions are known to stay within the lumen of blood vessels and not leak into capillaries (pg. 248, left column, first paragraph). The examiner notes that the teachings of Mattrey 1989 demonstrate that it is understood by skilled artisans in biomedical imaging that perfluorocarbons can be used to darken the lumen of organs imaged by MRI and are suitable for contrast usage in the form of an emulsion.
As pertinent art, the examiner cites Sigward (Sigward, E.; et al., Pharm. Res., 2015). Sigward teaches emulsions containing gadolinium chelate (pg. 2983, Title and Abstract). More specifically, Sigward teaches the preparation of Water/Oil/Water emulsions containing Gd-DTPA in the inner water component and demonstrates that such emulsions are useful as MRI contrast agents (pg. 2990, MRI; and pg. 2992, Figure 5 and Table VIII). The examiner notes that this demonstrates that gadolinium chelates are compatible in emulsion compositions and that gadolinium chelates in an aqueous phase do not cross into oil phases in stable emulsions. The teaches of Sigward also demonstrate the utility of gadolinium chelates in the form of an emulsion.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric P Mosher whose telephone number is (571)272-3258. The examiner can normally be reached Monday-Friday 9am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
Prosecution Insights