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 .
Applicant canceled claims 2 and 7.
In view of the amendment, previous 112(b) rejection on claims 1-20, previous 112(b) rejection on claims 2 and 3, and previous 112(b) rejection on claim 20 are hereby withdrawn.
In view of the amendment, previous 102(a)(1) and 103 rejections over Campbell et al’936 are hereby withdrawn. Thus, applicant’s arguments as to those previous rejections are now moot.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 3-6 and 8-20 are rejected under 35 U.S.C. 103 as being unpatentable over Campbell et al (US 2011/0142936 A1) in view of (i) Adams et al (US 2018/0303945 A1), Ramstack et al (US 6,495,164 B1) or Chen et al (US 2006/0141040 A1); and (ii) Delaney, JR. et al (US 2021/0060183 A1).
Campbell teaches (claim 1) a pharmaceutically acceptable implant system comprising a collection of pharmaceutically acceptable, covalently crosslinked hydrogel particles having a radiopaque agent covalently attached to a plurality of the crosslinked hydrogel particles in the collection, with the radiopaque agent being present in the collection at a concentration of at least about 0.1 wt.%. Campbell further teaches (claims 18-20 and [0134]) that its implant system contains (i) an applicator (a syringe – see [0134]) in which the crosslinked hydrogel particles (dehydrated) are disposed; and (ii) a container of physiological saline fluidly connectable to the applicator to mix the saline and particles in the applicator (so as to form injectable preformed hydrogel slurries that will be placed into the patient). Thus, Campbell teaches instant injectable suspension comprising radiopaque crosslinked hydrogel particles in a carrier fluid.
With respect to the carrier fluid comprising a linear hydrophilic polymers, Campbell teaches (claim 12) that the implant system of claim 1 further comprise an osmotic agent comprising a linear hydrophilic polymer in a mixture with the crosslinked hydrogel particles (as a means to improve the injectability of the crosslinked hydrogel particles through the catheter and/or needle of the syringe by reducing the force required to eject the hydrogel particles from the small gauge needle/catheter – see [0117]-[0119], [0019] and [0156]). Thus, Campbell teaches instant carrier fluid comprising a linear hydrophilic polymers.
With respect to the linear hydrophilic polymer being selected from a poly-2-oxazoline, a polyvinylpyrrolidone or a polyacrylamide, in its Example 5, Campbell uses linear PEG (a linear hydrophilic polymer) as the osmotic agent. Campbell’s linear PEG does not teach instant linear hydrophilic polymers. However, as evidenced by Adams et al ([0470] and [0459]) or Ramstack et al (abstract and col.1, lines 59-62, col.12, lines 58-64), it is well known in the art that polymers, such as polyvinylpyrrolidone, can be used as a viscosity enhancer in injectable suspensions of particles in order to make it easier to inject the suspension of particles (i.e., with low force on the syringe plunger) and thus improve injectability. Since a linear PEG and polyvinylpyrrolidone are individually taught to be useful for the same purpose (i.e., useful for improving the injectability of the suspensions of particles), it would have been obvious to one skilled in the art to use a linear PEG and polyvinylpyrrolidone together (as osmotic agents) in Campbell’s implant system with a reasonable expectation of improving the injectability of Campbell’s suspension of crosslinked hydrogel particles by making it easier to inject with low force on the syringe plunger. MPEP 2144.06 states that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Alternatively, as evidenced by Chen et al (claim 7, [0029] and [0030]), PEG (polyethylene glycol), polyvinylpyrrolidone and polyacrylamide are all known in the art as equivalent or interchangeable hydrophilic viscosity enhancers that are used to provide sufficiently high viscosity to an injectable suspension vehicle (so as to support the stable suspension). Thus, it would have been obvious to one skilled in the art to use polyvinylpyrrolidone or polyacrylamide (instead of PEG) as the linear hydrophilic polymer (Campbell’s osmotic agent) in Campbell’s implant system with a reasonable expectation of enhancing the viscosity of its injectable hydrogel slurries so as to support the stable suspension of the crosslinked hydrogel particles and improve the injectability. Thus, Campbell in view of Adams, Ramstack or Chen renders obvious instant linear hydrophilic polymer, which is polyvinylpyrrolidone or polyacrylamide.
With respect to instant radiopaque crosslinked hydrogel particles comprising a crosslinked polymer that comprises one or more of poly(N-vinyl pyrrolidone) chain, a poly(2-oxazoline) chain, or a polyacrylamide chain, in Example 5 ([0156]-[0157]; see also [0054]), Campbell uses covalently crosslinked multiarmed PEG hydrogel particles, which comprise a crosslinked polymer comprising a poly(ethylene oxide) chain. Such crosslinked polymer does not teach instant crosslinked polymer comprising one or more of a poly(N-vinyl pyrrolidone) chain, a poly(2-oxazoline) chain, or a polyacrylamide chain. However, Delaney, JR. et al teaches (see [0003], [0040], [0047], [0073]) the equivalence of PEG and polyoxazolines (such as poly(2-alkyl-2-oxazolines)), both as hydrophilic polymers that can form hydrophilic polymer arms of reactive multi-arm polymers, which are used in forming injectable crosslinked hydrogels. Thus, it would have been obvious to one skilled in the art to use covalently crosslinked multiarmed poly(2-alkyl-2-oxazoline) (instead of PEG) hydrogel particles comprising a crosslinked polymer that comprises a poly(2-alkyl-2-oxazoline) chain (instead of a poly(ethylene oxide) chain) in Campbell with a reasonable expectation of success. Besides, Campbell also teaches ([0039] and [0041]) the equivalence of PEG and PVP (instant polyvinylpyrrolidone), both as polymers that form hydrophilic portion of its precursors, which are crosslinked together to form covalently crosslinked hydrogels. Thus, it would be obvious to one skilled in the art to use covalently crosslinked multiarmed polyvinylpyrrolidone (instead of PEG) hydrogel particles comprising a crosslinked polymer that comprises a polyvinylpyrrolidone chain (instead of a poly(ethylene oxide) chain) in Campbell with a reasonable expectation of success. Thus, Campbell or Campbell in view of Delaney, JR renders obvious instant radiopaque crosslinked hydrogel particles comprising a crosslinked polymer that comprises a poly(2-oxazoline) chain or a poly(N-vinylpyrrolidone) chain.
Therefore, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claims 1 and 16-18.
With respect to instant claim 3, as discussed above, in its Example 5, Campbell uses linear PEG (a linear hydrophilic polymer) as the osmotic agent. Furthermore, the Examiner already established above that in view of the teaching of Adams, Ramstack or Chen, it would have been obvious to one skilled in the art to use polyvinylpyrrolidone or polyacrylamide (instead of PEG) (as Campbell’s osmotic agent) in Campbell’s implant system with a reasonable expectation of success. Campbell further teaches ([0119]) that its osmotic agent (linear hydrophilic polymer) can have a molecular weight between about 500 and about 100,000. Such molecular weight range overlaps with instant Mw range of 1kDa – 60k Da, thus rendering instant range prima facie obvious. In the case “where the [claimed] ranges overlap or lie inside ranges disclosed by the prior art,” a prima facie case of obviousness would exist which may be overcome by a showing of unexpected results, In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 3.
With respect to instant claim 4, Campbell’s Fig.11A shows that the its linear hydrophilic polymer (PEG, which is to be replaced by polyvinylpyrrolidone or polyacrylamide according to the teachings of Adams, Ramstack; or Chen as discussed above) was used in its Example 5 in the amount of 5%, 10%, 15% and 20%. Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 4.
With respect to instant claims 5 and 6, as discussed above, Campbell teaches (claim 1) that the radiopaque agent is covalently attached to a plurality of its crosslinked hydrogel particles and further teaches (claim 8) that the radiopaque agent comprises iodine. Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claims 5 and 6.
With respect to instant claim 8, Campbell teaches ([0047]-[0048]) that the precursors for its crosslinked hydrogel may have, e.g., 2-100 arms, with each arm having a terminus where “an arm” on the hydrogel precursor refers to a linear chain of chemical groups that connect a crosslinkable functional group to a polymer core. Campbell teaches that its crosslinked hydrogels can be made from a multi-armed precursor with a first set of functional groups (e.g., a six- or eight-armed precursor having hydrophilic polyethylene glycol (PEG) arms that are terminated with primary amine groups) and a low molecular-weight precursor having a second set of functional groups. Once these precursors are covalently crosslinked with each other, they form a crosslinked hydrogel ([0032]). Furthermore, the Examiner established above that based on Delaney, JR.’s teaching of equivalence of PEG arm and polyoxazoline arm, it would be obvious to one skilled in the art to use covalently crosslinked multiarmed poly(2-alkyl-2-oxazoline) (instead of PEG) hydrogel particles comprising a crosslinked polymer that comprises a poly(2-alkyl-2-oxazoline) chain (instead of a poly(ethylene oxide) chain) in Campbell with a reasonable expectation of success. Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 8.
With respect to instant claim 9, Campbell gives an example (see Example 4 in [0154]; the footnote under Table III; and [0080]), an 8a20kSGA PEG with 3-4 terminal TIB (31% substitution) or about 5 terminal TIB (61% substitution), which refers to a 8-armed PEG of 20,000 Mw with SGA (succinimidyl glutarate) functional groups at the termini of arms, where 3-4 terminal SGA or 5 terminal SGA groups are substituted with TIB (triiodobenzoate which is a molecule that contains three iodines -instant radiopaque-atom). Thus, Campbell teaches a portion of plurality of polymer arms comprising a radiopaque-atom-containing moiety at the end. Furthermore, as already discussed above, the Examiner established above that it would be obvious (in view of Delaney, JR.’s teaching) to replace PEG chain (i.e., PEG arm) with poly(2-alkyl-2-oxazoline) chain (i.e., poly(2-alkyl-2-oxazoline) arm) in Campbell’s multiarmed polymer. Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 9.
With respect to instant claim 10, in Example 4, Campbell teaches that the 8a20kSGA PEG with 3-4 terminal TIB or about 5 terminal TIB was reacted with trilysine to make the hydrogels. The SGA (succinimidyl glutarate) moieties teach instant first reactive moieties that comprise electrophilic groups (see [0046] of present specification). The trilysine (composed of three L-lysine amino acid residues linked together by standard peptide bonds) teaches instant reactive compound having a plurality of second reactive moieties that comprise nucleophilic groups (see [0054] of present specification). Furthermore, as already discussed above, the Examiner established above that it would be obvious (in view of Delaney, JR.’s teaching) to replace PEG chain (i.e., PEG arm) with poly(2-alkyl-2-oxazoline) chain (i.e., poly(2-alkyl-2-oxazoline) arm) in Campbell’s multiarmed polymer (i.e., 8a20kSGA PEG with 3-4 terminal TIB or about 5 terminal TIB). Therefore, Campbell in view of Delaney, JR renders obvious instant radiopaque crosslinked hydrogel particles comprising a crosslinked reaction product of (a) a reactive multi-arm polymer containing a plurality of first reactive moieties that comprise electrophilic groups and (b) a reactive compound having a plurality of second reactive moieties that comprise nucleophilic groups. Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 10.
With respect to instant claim 11, in its Example 4 (see [0154]-[0155]), Campbell teaches injectable suspension containing 5% or 10% solids hydrogel (with bound iodine). Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 11.
With respect to instant claim 12, Campbell teaches that its collection of the covalently crosslinked hydrogel particles are spheroidal with a maximum diameter of about 20-200 microns. Such range falls within instant range 10-1500 microns and thus teaches instant range of claim 12. Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 12.
With respect to instant claim 13, Campbell first teaches ([0057] and [0134]) that buffers may be included in the hydrogels introduced into a body. Campbell also teaches in [0057] that the reaction rate of NHS (N-hydroxysuccinimide ester)-based crosslinking reactions (such as the crosslinking reaction between SGA functional group and trilysine as discussed above) may be delayed by keeping the reactant solutions at lower pH (pH 4-7). Campbell teaches ([0069]) that increasing the number of crosslinks content will affect the mechanical properties of the hydrogel, with more crosslinks making the gel more brittle and stronger. Campbell teaches that these factors can also increase degradation time. Based on such teachings of Campbell, it would have been obvious to one skilled in the art to have the saline fluid in its implant system to contain an acidic buffer so as to achieve a lower pH (4-7) with a reasonable expectation of delaying further crosslinking reaction (between SGA group and trilysine) and thus controlling the mechanical properties of the hydrogel to reduce the degradation time. The pH range of 4-7 overlaps with instant pH range 3-6.5, thus rendering instant range prima facie obvious. In re Wertheim, supra. Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 13.
With respect to instant claim 14, Campbell teaches (claim 21) that its implant system further comprises a therapeutic agent. Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 14.
With respect to instant claim 15, in Campbell’s Example 4, its injectable suspension of the radiopaque crosslinked hydrogel particles made by reacting 8a20kSGA PEG having 5 terminal TIB (61% substitution) with trilysine is shown to have a radiopacity of 155 HU (for 5% solids hydrogel) or 280 HU (for 10% solids hydrogel). Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claim 15.
With respect to instant claims 19 and 20, Campbell teaches (claim 37) a method of treating a patient with its pharmaceutically acceptable implant system by implanting (injecting) the collection of the covalently-crosslinked hydrogel particles. Campbell further teaches ([0100], [0124] and [0125]) that such implanted crosslinked hydrogel particles can be used as a fiduciary marker, for tissue augmentation or as spacers (to separate tissues to reduce a dose of radioactivity received by one of the tissues). Thus, Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR renders obvious instant claims 19 and 20.
It is to be noted that instant 103 rejection over Campbell in view of (i) Adams, Ramstack or Chen; and (ii) Delaney, JR can be overcome by incorporating the subject matter of instant claim 21 (the cited prior art does not teach or suggest the combination of instant crosslinked polymer comprising the poly(2-oxazoline) chain and instant linear hydrophilic polymer comprising the poly-2-oxazoline as required in instant claims 21 and 22).
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, 8-13, 15-18, 21 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 9-15 and 20 of copending Application No. 19/214,553 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reason.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 7, 9, 10 and 20 of App.’553 teach a hydrogel particle suspension where the radiopaque crosslinked hydrogel particles (formed in the method of claim 1 of App.’553) are suspended in a carrier fluid comprising a linear polymer having Mw of 5-20 kDa, such as polyoxazoline, polyvinylpyrrolidone or polyacrylamide, all of which are instant linear hydrophilic polymers of claim 1. Claim 11 of App.’553 teaches that the hydrogel particle suspension is contained in a preloaded syringe. Claim 12 of App.’553 teaches that the preloaded syringe is packaged together with a needle (instant delivery device). Claim 13 of App.’553 teaches that the radiocontrast agent (used in forming the radiopaque crosslinked hydrogel particles of claim 1) comprises an iodinated organic compound. Claim 14 of App.’553 teaches that the multi-arm polymer (used in the method of claim 1 to form the radiopaque crosslinked hydrogel particles) comprises 3 or more polymer arms linked to a core region, each of the polymer arms comprising a hydrophilic polymer segment and cyclic imide ester end group, and claim 15 of App.’553 teaches that such hydrophilic polymer segment can be polyoxazoline segments (thus, claims of App.’553 teach instant radiopaque crosslinked hydrogel particles comprising a crosslinked polymer that comprises a poly(2-oxazoline) chain).
Thus, claims of App.’553 render obvious instant claims 1, 3, 5, 6, 8 and 15-18 (since the claims of App.’553 teach instant injectable suspension of claim 1, it is the Examiner’s position that such injectable suspension would naturally have a radiopacity that is greater than 100 HU as recited in instant claim 15).
With respect to instant claims 4, 11 and 12, it is the Examiner’s position that determining instant range for the amount of the linear hydrophilic polymers contained in the carrier fluid, instant range for the amount of the radiopaque crosslinked hydrogel particles based on the total weight of the suspension and instant range for the longest dimension of the radiopaque crosslinked hydrogel particles that would give the optimal performance in injecting the suspension of the radiopaque crosslinked hydrogel particles would be within the realm of one of ordinary skill in the art. Thus claims of App.’553 render obvious instant claims 4, 11 and 12.
With respect to instant claim 9, although claims of App.’’553 do not explicitly teach that a portion of the polymer arms comprise a radiopaque-atom-containing moiety at the end, claim 13 of App.’553 teaches that the radiocontrast agent of claim 1 comprises an iodinated organic compound, and since the method of forming radiopaque crosslinked hydrogel particles as described in claims of App.’553 is the same as that of applicant, it is the Examiner’s position that the radiopaque-atom-moiety (of the radiopaque crosslinked hydrogel particles in claims of App.’553) would naturally be located at the end of the polymer arms as instantly recited in claim 9. Thus, claims of App.’553 render obvious instant claim 9.
With respect to instant claim 10, claim 1 of App.’553 teaches a crosslinked reaction product of a multi-arm polymer comprising a plurality of cyclic imide ester groups (instant electrophilic group) and a reactive multifunctional compound comprising a plurality of amino groups (instant nucleophilic groups). Thus, claims of App.’553 render obvious instant claim 10.
With respect to instant claim 13, claim 8 of App.’553 teaches that the carrier fluid has a pH of 3.5-6.5 (which implies the presence of an acidic buffer). Thus, claims of App.’553 render obvious instant claim 13.
With respect to instant claims 21 and 22, as already discussed above, claims of App.’553 teach instant crosslinked polymer comprising poly(2-oxazoline) chain and instant liner hydrophilic polymer comprising poly-2-oxazoline. Thus, claims of App.’553 render obvious instant claims 21 and 22.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SIN J. LEE whose telephone number is (571)272-1333. The examiner can normally be reached on M-F 9 am-5:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Kwon can be reached on 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SIN J LEE/
Primary Examiner, Art Unit 1613
August 2, 2026
Prosecution Insights