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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 8/26/2026 is acknowledged.
Claims 17-20 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II and III, and there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/26/2026
Status of Claims
Withdrawn: 17-20
Examined Herein: 1-16
Priority
Acknowledgment is made of applicant's claim for priority under based upon an application filed in PRO 63/488,043 on 3/2/2023 and PCT/US2024/017807.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/20/2024 and 6/24/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings received on 2/29/2024 are accepted.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 6, 10-13, 15, and 16 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Reb (US 2016/0200670 A1, Published 7/14/2016).
With respect to claim 1 and 10, Reb discloses a radiopaque particulate composition comprising a radiopaque crosslinked acrylamide copolymer that comprises:
(a) a monofunctional acrylamide monomer containing radiopaque atoms (disodium 5-(4-acrylamidobutanamido)-2,4,6-triiodoisophthalate); and
(b) a multifunctional acrylamide monomer that does not contain radiopaque atoms (N,N'-methylenebis acrylamide));
wherein the composition comprises at least one multifunctional acrylamide monomer that does not contain radiopaque atoms, thus meeting the limitations of claim 1 and 10. [Reb, 0080-0141]
With respect to claim 2, Reb discloses that the monofunctional acrylamide monomer comprises a single acrylamido moiety and an iodinated moiety, thus meeting the limitations of claim 2. [Reb, 0080-0141]
With respect to claim 3, Reb discloses that the iodinated moiety is an iodinated aromatic group, thus meeting the limitations of claim 3. [Reb, 0080-0141]
With respect to claim 6, Reb discloses that the monofunctional acrylamide monomer comprises a phenyl group substituted with (a) three iodine atoms and (b) one acrylamide moiety, thus meeting the limitations of claim 6. [Reb, 0080-0141]
With respect to claim 11, Reb discloses that the composition further comprises an imaging agent (ferucarbotran) or a therapeutic agent, doxorubicin, thus meeting the limitations of claim 11. [Reb, 0129, 0138]
With respect to claim 12, Reb discloses that radiopaque particles have an average size of 260-402 microns, thus meeting the limitations of claim 12. [Reb, 0128]
With respect to claim 13, Reb discloses that the composition is injectable, thus meeting the limitations of claim 13. [Reb, 0061-0063, 0072]
With respect to claims 15 and 16, Reb discloses that the composition is in a suspension, thus meeting the limitations of claims 15 and 16. [Reb, 0130, 0141] The limitation "wherein the radiopaque particulate composition is provided in a container" does not functionally or structurally alter the radiopaque particulate composition, and therefore is owed no patentable weight. Nonetheless, Reb discloses that the particulate composition is provided in a vial. [Reb, 0130, 0141]
Claims 1-3, 6, and 8 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Cruise (US 2009/0164013 A1, Published 6/25/2009).
With respect to claim 1, Cruise discloses a radiopaque crosslinked acrylamide copolymer comprising:
(a) a monofunctional acrylamide monomer containing one or more radiopaque atoms (5 acrylamido-2,4,6-triiodo-n,n'-bis-(2,3 dihydroxypropyl) isophthalamide); and
(b) a multifunctional acrylamide monomer that does not contain one or more radiopaque atoms (PEG diacrylamide);
wherein the copolymer comprises at least one multifunctional acrylamide monomer that does not contain one or more radiopaque atoms, thus meeting the limitations of claim 1. [Cruise, 0059]
With respect to claim 2, Cruise discloses that the monofunctional acrylamide monomer comprises a single acrylamido moiety and an iodinated moiety, thus meeting the limitations of claim 2. [Cruise, 0059]
With respect to claim 3, Cruise discloses that the iodinated moiety comprises an iodinated aromatic group, thus meeting the limitations of claim 3. [Cruise, 0059]
With respect to claim 6, Cruise discloses that the monofunctional acrylamide monomer comprises a phenyl group substituted with (a) three iodine atoms, (b) one acrylamido moiety, thus meeting the limitations of claim 6. [Cruise, 0059]
With respect to claim 8, Cruise discloses that the copolymer is a hydrogel, thus meeting the limitations of claim 8. [Cruise, 0059]
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.
Claims 1-3, 6, and 9-16 are rejected under 35 U.S.C. 103 as being unpatentable over Reb, as applied to claims 1-3, 6, 10-13, 15, and 16 above, further in view of Hohn (US 2016/0228556 A1, Published 8/11/2016).
With respect to claim 1, Reb discloses the teachings above.
With respect to claim 14, Reb discloses that the composition is in dry (lyophilized) form. [Reb, 0122] The limitation "wherein the radiopaque particulate composition is provided in a container" does not functionally or structurally alter the radiopaque particulate composition, and therefore is owed no patentable weight. Nonetheless, Reb discloses that the particulate composition is provided in a container (a vial). [Reb, 0130, 0141]
Reb does not disclose that the radiopaque crosslinked acrylamide copolymer has a radiopacity that is greater than 100 Hounsfield units (HU). (Claim 9) Reb does not disclose that the particulate composition is sterile. (Claim 14)
However, with respect to claim 9, Hohn discloses a particulate composition comprising radiopaque material covalently attached to a polymer. [Hohn, 0029] Hohn discloses that the radiopaque material may be halogenated (e.g. iodinated) phenyl groups, which are useful because they can be mono-, di-, tri- or even tetra-substituted in order to control the amount of the halogen, such as iodine, that is incorporated into the radiopaque polymer, and hence control the level of radiopacity. [Hohn, 0055] Hohn discloses that the composition is preferred to have a radiopacity of greater than 100 HU and, more preferably greater than 500 HU, including greater than 2000, 3000, 4000, or 5000 HU. Radiopacity at these levels allows the microspheres to be differentiated from blood (30-45 HU), liver (40-60 HU), brain (20-45 HU), and soft tissue (100-300 HU), for example. [Hohn, 0064]
With respect to claim 14, Hohn discloses that the particulate composition is in dry (lyophilized) form and sterile. [Hohn, 0166, 0172]
Modifying the copolymer disclosed by Reb so that it achieves a radiopacity that is greater than 100 Hounsfield units (HU) results in the copolymer of claim 9.
Modifying the copolymer disclosed by Reb so that it is sterile results in the copolymer of claim 14.
It would be obvious to one of ordinary skill in the art to modify the copolymer disclosed by Reb so that it achieves a radiopacity that is greater than 100 Hounsfield units (HU) and have a reasonable expectation of success. Reb discloses a particulate composition comprising a radiopaque material (iodinated phenyl moiety) covalently attached to a crosslinked acrylamide polymer. Hohn discloses a particulate composition comprising radiopaque material (e.g., iodinated phenyl groups) covalently attached to a polymer. Hohn further discloses that the iodinated phenyl groups can be mono-, di-, tri- or even tetra-substituted and used to control the amount of iodine that is incorporated into the radiopaque polymer, thereby controlling the level of radiopacity. Hohn discloses that the composition is preferred have a radiopacity of greater than 100 HU and, more preferably greater than 500 HU, including greater than 2000, 3000, 4000, or 5000 HU. Accordingly, the combined teachings of Reb and Hohn reasonably suggest that the particulate composition disclosed by Reb is capable of achieving a radiopacity greater than 100 HU via the substituted iodinated phenyl moiety comprised within. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Hohn discloses that a radiopacity greater than 100 HU allows the microspheres to be differentiated from blood (30-45 HU), liver (40-60 HU), brain (20-45 HU), and soft tissue (100-300 HU), for example. [Hohn, 0064] Therefore, one would have been motivated to modify the copolymer disclosed by Reb to achieve a radiopacity that is greater than 100 Hounsfield units (HU) so that it can be differentiated from blood, liver, brain, and soft tissue during imaging.
It would be obvious to one of ordinary skill in the art to modify the composition disclosed by Reb so that it is sterile and have a reasonable expectation of success. Reb discloses a particulate composition (in dry form) comprising a radiopaque material covalently attached to a crosslinked acrylamide polymer. Hohn discloses a particulate composition (in dry form) comprising radiopaque material covalently attached to a polymer in lyophilized form. Hohn further discloses that the particles are gamma sterilized. Accordingly, the combined teachings of Reb and Hohn reasonably suggest that the particulate composition disclosed by Reb may be rendered sterile by subjecting it to a sterilization technique. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, sterilization techniques are known in the art and routinely performed to eliminate microorganisms from a product that it is applied to. Therefore, one would have been motivated by the expectation that the composition disclosed by Reb, when sterile, would be essentially free of microorganisms.
Claims 1, 4, 5, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Cruise, in view of Lux (Metal Chelating Crosslinkers Form Nanogels with High Chelation Stability, J Mater Chem B., 2013 Dec 14; 1(46):6359-6364).
With respect to claim 1, Cruise discloses a radiopaque crosslinked acrylamide copolymer comprising:
(a) a multifunctional acrylamide monomer that does not contain one or more radiopaque atoms (PEG diacrylamide); and
(b) a multifunctional acrylamide monomer that does not contain one or more radiopaque atoms (N,N-methylenebisacrylamide);
wherein the copolymer comprises at least one multifunctional acrylamide monomer that does not contain one or more radiopaque atoms. [Cruise, 0057]
With respect to claim 8, Cruise discloses that the copolymer is a hydrogel. [Cruise, 0059]
Cruise further discloses that the N,N-methylenebisacrylamide functions as an ethylenically unsaturated monomer with a visualization agent. [Cruise, 0038] Visualization agents may include radiopaque elements comprising an aromatic ring having a single unsaturation point and at least one iodine atom, tantalum, barium, salts thereof, or combinations thereof. [Cruise, 0012] However, Cruise discloses that the ethylenically unsaturated monomer may be monofunctional or multifunctional and may comprise a visualization agent that does or does not impart radiopacity. [Cruise, 0038] Example 3 exemplifies the embodiment of the co-polymer wherein the ethylenically unsaturated monomer is multifunctional and comprises a visualization agent that does not impart radiopacity. [Cruise, 0058]
Cruise does not disclose that the copolymer comprises a monofunctional or multifunctional acrylamide monomer that contains one or more radiopaque atoms.
However, with respect to claim 1, Lux discloses the following compound, N,N'-(5-lodo-1,3-phenylene)bis[2-acrylamide]:
PNG
media_image1.png
197
273
media_image1.png
Greyscale
[Lux, Page 10, Scheme 1]
N,N'-(5-iodo-1,3-phenylene)bis[2-acrylamide] is a derivative of N,N-methylenebisacrylamide and a multifunctional acrylamide monomer containing radiopaque atoms.
With respect to claim 4, Lux discloses that the multifunctional acrylamide monomer comprises two acrylamido moieties and an iodinated moiety. [Lux, Page 10, Scheme 1]
With respect to claim 5, Lux discloses that the iodinated moiety comprises an iodinated aromatic group. [Lux, Page 10, Scheme 1]
With respect to claim 7, Lux discloses that the multifunctional acrylamide monomer comprises a phenyl group substituted with (a) one iodine atom and (b) two acrylamido moieties. [Lux, Page 10, Scheme 1]
Modifying the polymer disclosed by Cruise by replacing N,N-methylenebisacrylamide with N,N'-(5-iodo-1,3-phenylene)bis[2-acrylamide] results in the copolymer of claim 1, 4, 5, and 7, wherein the copolymer comprises:
(a) a multifunctional acrylamide monomer that does not contain one or more radiopaque atoms (PEG diacrylamide); and
(b) a multifunctional acrylamide monomer that does contain radiopaque atoms (N,N'-(5-iodo-1,3-phenylene)bis[2-acrylamide];
It would be obvious to one of ordinary skill in the art to modify the polymer disclosed by Cruise by replacing N,N-methylenebisacrylamide with N,N'-(5-iodo-1,3-phenylene)bis[2-acrylamide]Cruise discloses a copolymer comprising a multifunctional ethylenically unsaturated monomer with a visualization agent that does not impart radiopacity, N,N-methylenebisacrylamide. Cruise further discloses that the multifunctional ethylenically unsaturated monomer may alternatively comprise a visualization agent that does impart radiopacity. Lux discloses a multifunctional acrylamide monomer N,N'-(5-iodo- 1,3-phenylene)bis[2-acrylamide], which comprises an aromatic ring with one iodine atom that enables the monomer to impart radiopacity. Accordingly, the combined teachings of Cruise and Lux reasonably suggest that N,N'-(5-iodo-1,3-phenylene)bis[2-acrylamide] is a multifunctional ethylenically unsaturated monomer with a visualization agent (aromatic ring with one iodine atom) that does impart radiopacity, and therefore, may replace N,N-methylenebisacrylamide as the multifunctional ethylenically unsaturated monomer with a visualization agent in the copolymer. One would have been motivated to do so because it is prima face obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Cruise discloses that the ethylenically unsaturated monomers comprising radiopaque elements serve to impart radiopacity to the resulting polymer and enables the polymer to be visualized during or after implantation. [Cruise, 0034-0036] Therefore, one would have been motivated by the expectation that modifying the polymer disclosed by Cruise by replacing N,N-methylenebisacrylamide with N,N'-(5-iodo-1,3-phenylene)bis[2-acrylamide] would enable the polymer to be visualized during or after implantation.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 6, 8-16 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 8, 10, 11, 13-18 of copending Application No. 19/288,214 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Although the claims at issue are not identical, they are not patentably distinct from each other
because the present invention discloses overlapping subject matter with the reference claims, and granting a patent to the present application would give rise to an unjustified extension of the rights granted in the reference application. Both sets of claims (instant claims 1-3, 6, 10; reference claim: 1, 5, 8, 13) are directed to a radiopaque crosslinked acrylamide copolymer or particulate composition comprising the copolymer comprising:
An iodinated monofunctional acrylamide monomer that comprises a single acrylamido group and an iodinated aromatic (i.e., phenyl) group linked to the acrylamido,
A monofunctional acrylamide monomer that does not contain radiopaque moieties (i.e., an iodinated aromatic group, and
A multifunctional acrylamide monomer that does not contain radiopaque moieties (i.e., an iodinated aromatic group.
The copolymer may additionally comprise:
A multifunctional acrylamide monomer that does contain radiopaque moieties (i.e., iodinated aromatic groups).
Instant claims 8, 9, 11, 12, 13, 14/15/16 are drawn to the same limitations as reference claims 10, 11, 14, 15, 16, and 17/18, respectively.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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, Michael Hartley can be reached at 571-272-0616. 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.
/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
Prosecution Insights