RADIOPAQUE MONOMER AND EMBOLISATION MICROSPHERES COMPRISING SAME

§103 §DOUBLEPATENT

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 . Summary Claims 1-20 are pending in this office action. All pending claims are under examination in this application. Priority The current application was filed on December 27, 2024 is a 371 of PCT/EP2023/067727 filed June 28, 2023. The current application claims foreign priority to EP22305941.1 filed June 28, 2022. Information Disclosure Statement Receipt of the Information Disclosure Statement filed on March 5, 2025 is acknowledged. A signed copy of the document is attached to this office action. Claim Objections Claims 2-3, 6, 8, 11, 15, and 18 are objected to because of the following informalities: Claim 2: Please amend a comma after the text “…as defined in claim 1…”. Claim 3: Please amend the text to read “…wherein Z represents…”. Also, within c) Please amend the text to read “…[CH2=(CR16)]…” and later “…wherein R16 independently represents…”. Claim 6: Please amend the text to read “…[CH2=(CR16)]CO- or [CH2=(CR16)]CO-O- …”. Claim 8: Please delete bullet point four. Also, please add an “and” after bullet point two. Claim 11: Please amend the text to insert the plural form of mixture (…mixtures thereof.). Claim 15: Please delete the text “…on the one hand…” and “…on the other hand…”. Claim 18: Please amend bullet point four of claim 8 here. Appropriate correction is required. Claim Rejections - 35 USC § 103 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. 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 non-obviousness. 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. Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Beilvert et al. (US2023/0285601A1*) in view of Jayakrishnan et al. (Journal of Applied Polymer Science, 1992). [The Examiner is going to introduce each reference and then combine them where appropriate to reject the instant claims. *For ease of examination, the Examiner relied upon US Publication 2023/0285601A1 as an equivalent English translation of the French WO 2021/069528A1 (published April 15, 2021) publication. All citations henceforth to Beilvert et al. are locations in the US Publication.] 1. Beilvert et al. Beilvert et al. is the closest prior art to the claimed invention as it teaches non- degradable radio-opaque embolisation microspheres (see title). Additionally, Beilvert et al. disclose that the invention relates to a polymer comprising a crosslinked matrix, the matrix being based on at least: a) 20 to 90% hydrophilic monomer; b) 5 to 50% radio-opaque halogenated monomer; c) 1 to 15% non-biodegradable hydrophilic crosslinking agent; and d) 0.1 to 10% transfer agent chosen among the alkyl halides and cycloaliphatic or aliphatic thiols having, in particular, 2 to 24 carbon atoms, and optionally having another functional group chosen among the amino, hydroxy and carboxy groups. The invention further relates to a pharmaceutical composition comprising at least one polymer according to the invention, in association with a pharmaceutically acceptable vehicle, advantageously for a parenteral administration. The invention further relates to a kit comprising a pharmaceutical composition comprising the polymer according to the invention in association with a pharmaceutically acceptable vehicle for a parenteral administration, and an injection means (see abstract). 2. Jayakrishnan et al. Jayakrishnan et al. teach synthesis and polymerization of some iodine-containing monomers for biomedical applications (see title). In addition, Jayakrishnan et al. disclose triiodophenol and iothalamic acid (5-acetamido-2,4,6-triiodo-N-methyl isophthalamic acid) were converted to their acrylic derivatives by esterification with methacryloyl chloride and 2-hydroxyethyl methacrylate (HEMA), respectively. The monomers due to presence of heavy iodine atoms were expected to be radiopaque in nature. The monomers were characterized using TLC, IR, and 1H-NMR spectroscopy. Both monomers were highly resistant to homopolymerization and copolymerization with other acrylic monomers such as methyl methacrylate (MMA) or HEMA by initiators such as 2,2'-azobis isobutyronitrile (AIBN) or benzoyl peroxide (BPO) yielding only polymers of low molecular weight. The polymers obtained were characterized by gel permeation chromatography (GPC) and differential thermal analysis (DTA). The resistance to polymerization is presumably due to the presence of bulky iodine atoms in the monomers sterically hindering the propagation step. The decomposition temperatures of the homopolymers and copolymers were close to 300°C. Copolymers of HEMA with both radiopaque monomers incorporated to the extent of 25 wt % in the feed, however, produced polymers with good radiopacity. Copolymers with HEMA were also prepared in the form of microspheres by a solvent evaporation method with the aim of using them as particles in therapeutic embolization. While the polymer based on triiodophenol was found to cause extensive blood haemolysis within in vitro tests, polymer based on iothalamic acid was found to be nonhemolytic in character suggesting that copolymers based on iothalamic acid would be suitable for implantation in the living tissue (see abstract). Combination of Beilvert et al. and Jayakrishnan et al. Regarding instant claim 1, Beilvert et al. and Jayakrishnan et al. teach a compound of formula (A). The necessary citations within Beilvert et al. and Jayakrishnan et al. that pertain to instant claim 1 are presented in Table I. Table I Instant Claim 1 Beilvert et al. and Jayakrishnan et al. Citations A compound of formula (A): Beilvert et al. disclose non-degradable radio-opaque embolisation microspheres comprising numerous halogenated monomers represented by the following preferred halogenated compound set: PNG media_image1.png 200 400 media_image1.png Greyscale (see paragraph [0106]; abstract and claims; all within Beilvert et al.). PNG media_image2.png 200 332 media_image2.png Greyscale Jayakrishnan et al. disclose triiodophenyl methacrylate: PNG media_image3.png 200 400 media_image3.png Greyscale (see page 745, right column within Jayakrishnan et al.). Therefore, a skilled artisan (POSITA; person of ordinary skill in the art) would create under routine synthetic procedures a polyethylene glycol (PEG) linker between the methacrylate moiety and the triiodophenol portion, similar to the above analogues Vb-Vd disclosed by Beilvert et al. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the composition of Beilvert et al. with the teachings of Jayakrishnan et al. The motivation to combine the two references would be to synthesize a PEG linked triiodide methacrylate based off on TIPM, using the teachings of Beilvert et al. as examples of PEG linked methacrylates with aryl iodide analogues. This would create a novel radio-opacity imaging agent. Regarding instant claims 2 and 10, Beilvert et al. and Jayakrishnan et al. teach a method of medical imaging, comprising administering to a patient in need thereof an effective dose of compound of formula (A) as defined in claim 1 as halogenated radiopaque monomer. Beilvert et al. disclose wherein the matrix is further based on particles visible in magnetic resonance imaging (MRI) (see claim 10 within Beilvert et al.). Regarding instant claim 3, Beilvert et al. and Jayakrishnan et al. teach radiopaque embolization microspheres comprising a crosslinked matrix, said matrix being based on at least: a) from 20% to 90% of hydrophilic monomer chosen from N-vinylpyrrolidone and a monomer of following formula (I):(CH2=CR-1)-CO-D (I) in which: D represents O-Z or NH-Z, Z representing (C1-C6)alkyl, -(CR2R3)m-CH3, -(CH2-CH2-O)m-H-, -(CH2-CH2-O)m-CH3, -C(R4OH)m or -(CH2)m-NR5R6 with m representing an integer from 1 to 30; R1, R-2, R3, R4, R5 and R-6 represent, independently of one another, H or a (C1-C6)alkyl; b) from 5% to 50% of compound of following formula (A); c) from 1% to 15% of nonbiodegradable linear or branched hydrophilic crosslinking monomer exhibiting (CH2=(CR16))- groups at each of its ends, each R16 independently representing H or a (C1-C6)alkyl; and d) from 0.1% to 10% of transfer agent being alkyl halides, cycloaliphatic thiols or aliphatic thiols, and optionally having another functional group chosen from amino, hydroxy and carboxy groups, the percentages of the monomers a) to c) being given in moles with respect to the total number of moles of monomers, and the percentages of the compound d) being given in moles with respect to the number of moles of the hydrophilic monomer a). Beilvert et al. disclose radiopaque embolization microspheres comprising a crosslinked matrix matching the limitations of instant claim 3 (see claim 1; paragraphs [0001], [0110], and [0223]; all within Beilvert et al.). Regarding instant claim 4, Beilvert et al. and Jayakrishnan et al. teach wherein the matrix is based on the compound of general formula (A) in an amount of greater than 7% and of less than or equal to 50% per mole, with respect to the total number of moles of monomers. Beilvert et al. disclose wherein the matrix is based on halogenated radiopaque monomer of general formula (A) in an amount greater than 7% and less than or equal to 50% (mol %), relative to the total number of moles of monomers (see claim 2 within Beilvert et al.). Regarding instant claim 5, Beilvert et al. and Jayakrishnan et al. teach the embolization microspheres of instant claim 3, wherein the hydrophilic monomer a) is selected from the group consisting of N-vinylpyrrolidone, vinyl alcohol, 2-hydroxyethyl methacrylate, sec-butyl acrylate, n-butyl acrylate, t-butyl acrylate, t-butyl methacrylate, methyl methacrylate, N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylate, t-butylaminoethyl (meth)acrylate, N,N-diethylaminoacrylate, poly(ethylene oxide) (meth)acrylate, methoxy poly(ethylene oxide) (meth)acrylate, butoxy poly(ethylene oxide) (meth)acrylate, poly(ethylene glycol) (meth)acrylate, methoxy poly(ethylene glycol) (meth)acrylate, butoxy poly(ethylene glycol) (meth)acrylate, poly(ethylene glycol) methyl ether methacrylate and mixtures thereof. Beilvert et al. disclose wherein the hydrophilic monomer a) is selected from the group represented within instant claim 5 (see claim 3 within Beilvert et al.). Regarding instant claim 6, Beilvert et al. and Jayakrishnan et al. teach wherein the nonbiodegradable linear or branched hydrophilic crosslinking monomer c) exhibits (CH2=(CR16))CO- or (CH2=(CR16))CO-O- groups at its at least two ends, each R16 independently representing H or a (C1-C6)alkyl. Beilvert et al. disclose wherein the nonbiodegradable linear or branched hydrophilic crosslinking monomer c) exhibits (CH2=(CR16))CO- or (CH2=(CR16))CO-O- groups at its at least two ends, each R16 independently representing H or a (C1-C6)alkyl (see claim 6 within Beilvert et al.). Regarding instant claim 7, Beilvert et al. and Jayakrishnan et al. teach wherein the transfer agent d) is thioglycolic acid, 2-mercaptoethanol, dodecanethiol, hexanethiol, or mixtures thereof. Beilvert et al. disclose wherein the transfer agent d) is thioglycolic acid, 2-mercaptoethanol, dodecanethiol, hexanethiol, or mixtures thereof (see claim 7 within Beilvert et al.). Regarding instant claim 8, Beilvert et al. and Jayakrishnan et al. teach wherein the matrix is in addition based on at least one ionized or ionizable monomer of the following formula (IV): (CH2=CR11)-M-E (IV) in which PNG media_image4.png 200 400 media_image4.png Greyscale Beilvert et al. disclose wherein the matrix is in addition based on at least one ionized or ionizable monomer of instant claim 8 (see claim 8 within Beilvert et al.). Regarding instant claim 9, Beilvert et al. and Jayakrishnan et al. teach wherein the matrix is in addition based on at least one colored monomer of following general formula (VI): PNG media_image5.png 200 400 media_image5.png Greyscale Beilvert et al. disclose wherein the matrix is in addition based on at least one colored monomer of instant claim 9 (see claim 9 within Beilvert et al.). Regarding instant claim 11, Beilvert et al. and Jayakrishnan et al. teach the microspheres charged with an active substance selected from the group consisting of anti-inflammatory agents, local anesthetics, analgesics, antibiotics, anticancer agents, steroids, antiseptics and mixtures thereof. Beilvert et al. disclose wherein the drug or the active substance is selected from the group consisting of anti-inflammatory agents, local anesthetics, analgesics, antibiotics, anticancer agents, steroids, antiseptics and a mixture thereof (see claim 20 within Beilvert et al.). Regarding instant claim 12, Beilvert et al. and Jayakrishnan et al. teach the embolization microspheres of instant claim 8, charged with macromolecules selected from the group consisting of enzymes, antibodies, cytokines, growth factors, clotting factors, hormones, plasmids, antisense oligonucleotides, siRNA, ribozymes, DNA enzyme, aptamers, anti-inflammatory proteins, bone morphogenetic proteins (BMP), pro-angiogenic factors, vascular endothelial growth factors (VEGF) and TGF-beta, angiogenesis inhibitors, antityrosine kinases, and mixtures thereof. Beilvert et al. disclose the embolization microspheres of instant claim 8, charged with macromolecules selected from the group of instant claim 12 (see claim 12 within Beilvert et al.). Regarding instant claim 13, Beilvert et al. and Jayakrishnan et al. teach a pharmaceutical composition comprising at least one embolization microsphere of instant claim 3, in combination with a pharmaceutically acceptable vehicle. Beilvert et al. disclose a pharmaceutical composition comprising at least one embolization microsphere of instant claim 3, in combination with a pharmaceutically acceptable vehicle (see claim 13 within Beilvert et al.). Regarding instant claim 14, Beilvert et al. and Jayakrishnan et al. teach a kit comprising a pharmaceutical composition as defined in instant claim 13, in combination with a pharmaceutically acceptable vehicle, for parenteral administration, and at least one means of injection. Beilvert et al. disclose a kit comprising a pharmaceutical composition as defined in instant claim 13, in combination with a pharmaceutically acceptable vehicle, for parenteral administration, and at least one means of injection (see claim 14 within Beilvert et al.). Regarding instant claim 15, Beilvert et al. and Jayakrishnan et al. teach a kit comprising, on the one hand, a pharmaceutical composition as defined in instant claim 13 and, on the other hand, at least one contrast agent for imaging by X-ray, by magnetic resonance or by ultrasonography, and optionally at least one means of injection for administration parenterally, the pharmaceutical composition and the at least one contrast agent being packaged separately. Beilvert et al. disclose a kit comprising, on the one hand, a pharmaceutical composition as defined in instant claim 13 and, on the other hand, at least one contrast agent for imaging by X-ray, by magnetic resonance or by ultrasonography, and optionally at least one means of injection for administration parenterally, the pharmaceutical composition and the at least one contrast agent being packaged separately (see claim 15 within Beilvert et al.). Regarding instant claim 16, Beilvert et al. and Jayakrishnan et al. teach the embolization microspheres of instant claim 3, wherein the matrix is based on the compound of general formula (A) in an amount from 20% to 30% per mole with respect to the total number of moles of monomers. Beilvert et al. disclose the embolization microspheres of instant claim 3, wherein the matrix is based on the compound of general formula (A) in an amount from 20% to 30% per mole with respect to the total number of moles of monomers (see paragraph [0154; radiopaque monomer] and abstract; both within Beilvert et al.). Regarding instant claim 17, Beilvert et al. and Jayakrishnan et al. teach the embolization microspheres of instant claim 3, wherein the hydrophilic monomer a) is poly(ethylene glycol) methyl ether methacrylate. Beilvert et al. disclose the embolization microspheres of instant claim 3, wherein the hydrophilic monomer a) is poly(ethylene glycol) methyl ether methacrylate (see paragraph [0084] within Beilvert et al.). Regarding instant claim 18, Beilvert et al. and Jayakrishnan et al. teach the embolization microspheres of instant claim 8, wherein in formula (IV), E is selected from the group consisting of -COOH, -COO-, -SO3H, -SO3-, -PO3H2, -PO3H-, -PO32-, -NR18R19 and -NR20R21R22+. Beilvert et al. disclose the embolization microspheres of instant claim 8, wherein in formula (IV), E is selected from the group consisting of -COOH, -COO-, -SO3H, -SO3-, -PO3H2, -PO3H-, -PO32-, -NR18R19 and -NR20R21R22+ (see claim 18 within Beilvert et al.). Regarding instant claim 19, Beilvert et al. and Jayakrishnan et al. teach the embolization microspheres of instant claim 9, wherein in formula (VI), R24 represents a -C6H4-O-(CH2)2-O or -C(CH3)2-CH2-O group. Beilvert et al. disclose the embolization microspheres of instant claim 9, wherein in formula (VI), R24 represents a -C6H4-O-(CH2)2-O or -C(CH3)2-CH2-O group (see claim 19 within Beilvert et al.). Regarding instant claim 20, Beilvert et al. and Jayakrishnan et al. teach the embolization microspheres of instant claim 10, wherein the matrix is additionally based on iron oxide nanoparticles, gadolinium chelates or magnesium chelates. Beilvert et al. disclose the embolization microspheres of instant claim 10, wherein the matrix is additionally based on iron oxide nanoparticles, gadolinium chelates or magnesium chelates (see paragraph [0150] within Beilvert et al.). Analogous Art The Beilvert et al. and Jayakrishnan et al. references are directed to the same field of endeavor as the instant claims, that is, a compound of formula (A), as disclosed within instant claim 1. Obviousness Analysis It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the non-degradable radio-opaque embolisation microspheres disclosed by Beilvert et al., using the teachings of Jayakrishnan et al. in order to arrive at the subject matter of the instant claims. The Beilvert et al. and Jayakrishnan et al. references all have considerable overlap in the radio-opaque embolisation microsphere arts. In this instant, Beilvert et al. supplies the template for the non-degradable radio-opaque embolisation microspheres, while Jayakrishnan et al. evidence of the triiodophenyl methacrylate (TIPM) en route to the radio-opaque monomer of instant claim 1. All references are directed to radio-opaque embolisation microspheres and therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the two references when seeking to develop an enhanced non-degradable radio-opaque embolisation microsphere. Given these teachings, a POSITA would have been motivated to combine the non-degradable radio-opaque embolisation microspheres as disclosed by Beilvert et al., and the triiodophenyl methacrylate (TIPM) monomer disclosed by Jayakrishnan et al. The modification constitutes a simple substitution of one known element for another to obtain a predictable result [MPEP §2143(I)(B)]. The combination represents the use of a known technique to improve a similar composition in the same way [MPEP §2143(I)(C)]. The art provides a finite number of identified, predictable solutions, and the POSITA would have pursued the claimed configuration with a reasonable expectation of success [MPEP §2143(I)(E); KSR]. The combination of the non-degradable radio-opaque embolisation microspheres taught by Beilvert et al. along with the use of the necessary claim limitations disclosed by Jayakrishnan et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application. Furthermore, the additional claim limitations taught by Jayakrishnan et al. would have been viewed by a POSITA as routine design optimizations or known modifications for halogenated aryl methacrylates comprising non-degradable radio-opaque embolisation microspheres. The motivation to combine the two references would be to synthesize a PEG linked triiodide methacrylate based off on TIPM, using the teachings of Beilvert et al. as examples of PEG linked methacrylates with aryl iodide analogues. This would create a novel radio-opacity imaging agent. Implementing these features in Beilvert et al.’s non-degradable radio-opaque embolisation microspheres would not require more than ordinary skill or routine experimentation. Accordingly, the combination of Beilvert et al. and Jayakrishnan et al. provides all the elements of the claimed invention. The resulting improved non-degradable radio-opaque embolisation microsphere, constitutes no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention. Double Patenting The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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 1-16 and 18-19 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 1-3 and 6-19 of co-pending Application No. 17/754,532 (reference application) in view of Jayakrishnan et al. Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and that of Application ‘532 encompass non-degradable radio-opaque embolisation microspheres. The difference between the instant claims and that of Application ‘532 is the use of compound MAETIP: PNG media_image2.png 200 332 media_image2.png Greyscale However, Jayakrishnan et al. teach synthesis and polymerization of some iodine-containing monomers for biomedical applications (see title). In addition, Jayakrishnan et al. disclose triiodophenol and iothalamic acid (5-acetamido-2,4,6-triiodo-N-methyl isophthalamic acid) were converted to their acrylic derivatives by esterification with methacryloyl chloride and 2-hydroxyethyl methacrylate (HEMA), respectively. The monomers due to presence of heavy iodine atoms were expected to be radiopaque in nature. The monomers were characterized using TLC, IR, and 1H-NMR spectroscopy. Both monomers were highly resistant to homopolymerization and copolymerization with other acrylic monomers such as methyl methacrylate (MMA) or HEMA by initiators such as 2,2'-azobis isobutyronitrile (AIBN) or benzoyl peroxide (BPO) yielding only polymers of low molecular weight. The polymers obtained were characterized by gel permeation chromatography (GPC) and differential thermal analysis (DTA). The resistance to polymerization is presumably due to the presence of bulky iodine atoms in the monomers sterically hindering the propagation step. The decomposition temperatures of the homopolymers and copolymers were close to 300°C. Copolymers of HEMA with both radiopaque monomers incorporated to the extent of 25 wt % in the feed, however, produced polymers with good radiopacity. Copolymers with HEMA were also prepared in the form of microspheres by a solvent evaporation method with the aim of using them as particles in therapeutic embolization. While the polymer based on triiodophenol was found to cause extensive blood haemolysis in in vitro tests, polymer based on iothalamic acid was found to be nonhemolytic in character suggesting that copolymers based on iothalamic acid would be suitable for implantation in the living tissue (see abstract). It would have been prima facie obvious to provide the triiodophenol and methacrylate moieties linked by a series of PEG groups from application ’532, and the end-group synthetic pieces of the TIPM analogue taught by Jayakrishnan et al. (see page 745, right column within Jayakrishnan et al.). There would have been a reasonable expectation of success in linking the two end groups with a series of PEG moieties based on the disclosure of Beilvert et al. (see paragraph [0106]; abstract and claims; all within Beilvert et al.). This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN W LIPPERT III whose telephone number is (571)270-0862. The examiner can normally be reached Monday - Thursday 9:00 AM - 5:00 PM. 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, Robert A Wax can be reached on 571-272-0623. 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. /JOHN W LIPPERT III/Examiner, Art Unit 1615