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 .
Status of Claims
Claims 1, 3-11, 13 and 21-23 are pending. Claims 2, 12 and 14-20 are canceled. Claims 22-23 are newly added.
Claims 4 and 21 are withdrawn, there being no linking or generic claim.
Claims 1, 3, 5-11, 13 and 22-23 are examined on their merits to the extent that the one or more photoreactive monomers is polyethylene glycol norbornene.
Previous Rejections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Rejections Withdrawn
Claim Rejections - 35 USC § 102
In light of the amendments to the claims the rejection of claims 1, 3, 5-11 and 13 under 35 U.S.C. 102(a)(1) as being anticipated by Lin US 2014/0112960 (4/24/2014) is withdrawn.
Double Patenting
In light of the amendments to the claims the provisional rejection of claims 1, 3, 5-11 and 13 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 9-10 and 25-30 of copending Application No. 18354636 in view of Lin US 2014/112960 (4/24/2014) is withdrawn.
In light of the amendments to the claims the provisional rejection of claims 1, 3, 5-11 and 13 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 17990195 in view of Lin US 2014/112960 (4/24/2014) is withdrawn.
New Rejections
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 3, 5-11, 13 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Lin US 2014/0112960 (4/24/2014) as evidenced by the specification and Lin et al. Thiol-norbornene photoclick hydrogels for tissue engineering applications, J Appl Polym Sci 2015 Feb 20; 132(8)(“J Appl”).
Lin is directed to a compositions comprising a visible light-curable mixture capable of forming a biocompatible hydrogel and hydrogels prepared from the hydrogel precursor mixtures. (See Abstract). The hydrogels are generally formed under radical polymerization conditions. Type II initiators are activated with light and extra hydrogen atoms from reactive thiol groups. The formed radical (R-S) reacts with a carbon-carbon multiple bond such as norbornene. (See [0036]). Alternatively, a step-growth polymerization can be utilized. Step growth polymerization provides a more organized and/or more regularly repeating pattern, structure or matrix as taught in figure (paragraph 0037).
Lin teaches that in general photo-polymerization for hydrogel synthesis are initiated by either long wavelength ultraviolet light or alternatively using visible light. (See [0005]).
Lin teaches monomers that are polyethylene glycol norbornene. (See [0206], [0181], Example 180). Polyethylene glycol norbornene has a methylene functional group and is called for in instant claim 3. The mixture further comprises a population of cells. (See Lin claim 7). Cells are called for in instant claim 1.
The crosslinker is a polythiol compound (See Lin claim 10). Cells are human mouse insulinoma (MIN6) beta-cells spheroids (See [0072], figure 22(a), [0035], [0147], and examples). Crosslinking agents include PEG dithiol which has from 20 to about 1000 repeat units (See [0086-0089]). PEG dithiol is called for in instant claim 6. (See [0076-0077]). PEG dithiol is a dithiol linker as called for in instant claim 6. The PEG dithiol has a molecular weight in the range from about 5000 to 40000 Da. (See [0113]). From about 5000 to 40000 Da overlaps with the molecular weight of from about 500 Da to about 10,000 Da as called for in instant claim 7.
In Example at paragraph [211] Lin teaches MIN6 β-cell spheroids are stained with Eosin-Y and PEG-dithiol. The coating of PEGSH introduced sulfhydryl groups used for thiol-ene crosslinking near the cell surface. PEG-norbornene macromer was used. The thiol labeled spheroids are contacted with PEG-norbornene macromer and crosslinking agent to form thiol-ene gel coated spheroids (See [211-212]).
Lin thus teaches an embodiment that is a composition that comprises a hydrogel which contains a polymer formed from the photoreactive monomer PEG norbornene and a PEG dithiol linker. PEG norbornene is a photoreactive monomer with a methylene group and PEG dithiol linker is a dithiol linker as called for in instant claims 8 and 1. PEG norbornene is an ultraviolet light photoreactive monomer as evidenced by J. Appl. (See Abstract “The gelation of thiol-norbornene hydrogels can be initiated by long-wave uv light or visible light without an additional coinitiator or comonomer”). An ultraviolet light photoreactive monomer is called for in instant claims 1, 7, 8, 9 and 11. Lin thus teaches a composition comprising a ultraviolet light curable mixture capable of forming a biocompatible hydrogel, the mixture comprising one or more macromers each comprising a methylene functional group and one or more crosslinking agents. (See Lin claim 1).
Lin teaches encapsulation of beta cells in a hydrogel formed of PEG norbornene and PEG dithiol in water and oil. Lin thus teaches a composition that contains a microcapsule that has a core containing a cell and polymeric shell in which the shell is made up of polymerized ultraviolet light photoreactive monomer (PEG norbornene) and a linker (PEG-dithiol) as called for in instant claim 1.
The thiol labeled spheroids are contacted with PEG-norbornene macromer and crosslinking agent to form thiol-ene gel coated spheroids (See [211-212]). The shell physically separates the cell from the external environment as called for in claim 22 because the cell is surrounded by the polymerized photoreactive monomer and a linker. This polymer is between the cell and any external environment because the spheroids are coated with the polymer.
It would have been prima facie obvious to one of ordinary skill in the art before the earliest effective filing date making the Lin composition to use ultraviolet light photoreactive monomer PEG norbornene and a PEG dithiol linker to encapsulate beta cells as taught by Lin in order to make a biocompatible hydrogel that can encapsulate beta cells without the need for an initiator and without the need to add cytotoxic co-monomers.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Lin US 2014/0112960 (4/24/2014) as evidenced by the specification and Lin et al. Thiol-norbornene photoclick hydrogels for tissue engineering applications, J Appl Polym Sci 2015 Feb 20; 132(8)(“J Appl”) as applied to claims 1, 3, 5-11, 13 and 23 and further in view of Murphy et al. US 2015/0293073 (10/15/2015).
The teachings of Lin are described supra. Lin does not teach lithium phenyl-2,4,6-trimethylbenzoylphosphinate. This deficiency is remedied by the teachings of Murphy et al.
Murphy et al. (Murphy) is directed to methods for forming patterned hydrogel arrays. (See Abstract). Murphy teaches that the patterned hydrogel arrays support the culture of a range of cell types. (See Abstract).
Murphy teaches that while biomaterial arrays such as self-assembled monolayers (“SAMs”) provide an excellent model substrate for investigating the effects of an immobilized ligand on cell behavior, preparing SAM array platforms using less labor intensive methods are needed to make SAM array use more widespread. (See [0011]).
Murphy teaches that suitable multifunctional polymer crosslinkers for use in the hydrogel precursor solution are known by those skilled in the art and polyethylene glycol dithiol is a particularly suitable polymer crosslinker. (See [0058]). Murphy teaches that the hydrogel precursor solution can further include an initiator. An initiator can induce polymerization and/or decrease the polymerization rate. (See [0059]). Murphy teaches that a particularly suitable photoinitiator is lithium phenyl-2,4,6-trimethylbenzoylphosphinate. (See [0059]).
It would have been prima facie obvious to one of ordinary skill in the art before the earliest effective filing date making the Lin composition of ultraviolet light photoreactive monomer PEG norbornene and a PEG dithiol linker to encapsulate beta cells to use lithium phenyl-2,4,6-trimethylbenzoylphosphinate as an initiator in order to have the ability to induce polymerization and decrease the polymerization rate as taught by Murphy.
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, 5-11, 13 and 22-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 9-10 and 25-30 of copending Application No. 18354636 in view of Lin US 2014/112960 (4/24/2014) and Murphy et al. US 2015/0293073 (10/15/2015).
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a composition, comprising: cells dispersed in or encapsulated within a hydrogel comprising a polymer made from a photoreactive monomer that is PEG-norbornene and a PEG-dithiol linker.
Copending ‘636 claims cells dispersed in or encapsulated within a hydrogel comprising a polymer made from a photoreactive monomer that is PEG-norbornene and a linker.
While copending ‘636 claims a linker, copending ‘636 does not expressly claim PEG diothiol linker or lithium phenyl-2,4,6-trimethylbenzoylphosphinate. However, this deficiency is cured by Lin and Murphy.
The teachings of Lin are described above. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘636 and Lin and utilize PEG dithiol as the crosslinker. One skilled in the art would have been motivated PEG dithiol as it is a crosslinker known to be used with PEG norbornene as taught by Lin. Since copending ‘636 claims a linker which can be utilized with PEG norbornene there is a reasonable expectation of success.
The teachings of Murphy are described above. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘636 and Murphy and add lithium phenyl-2,4,6-trimethylbenzoylphosphinate as an initiator in order to have the ability to induce polymerization and decrease the polymerization rate as taught by Murphy.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 5-11, 13 and 22-23 are directed to an invention not patentably distinct from claims 1-3, 5, 9-10 and 25-30 of copending Application No. 18354636 in view of Lin US 2014/112960 (4/24/2014) and Murphy et al. US 2015/0293073 (10/15/2015).
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between application or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned copending U.S. Patent Application No. 18354636, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualified as prior art under 35 U.S. C, 102(a)(2) and the patentably indistinct inventions were not commonly owner or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 101(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(v)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 USC 102(c) and 37 CFRR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the invention were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 USC 100(i) of the claimed invention will preclude a rejection under 35 USC 102 or 103 based upon the commonly assigned case. Alternative, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Claims 1, 3, 5-11, 13 and 22-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 17990195 in view of Lin US 2014/112960 (4/24/2014) and Murphy et al. US 2015/0293073 (10/15/2015).
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a composition, comprising: cells dispersed in or encapsulated within a hydrogel comprising a polymer made from a photoreactive monomer that is PEG-norbornene and a PEG-dithiol linker.
Copending ‘195 claims cells dispersed in or encapsulated within a hydrogel comprising a polymer made from a photoreactive monomer that is PEG-norbornene and a linker.
While copending ‘195 claims a linker, copending ‘195 does not expressly claim PEG diothiol linker or lithium phenyl-2,4,6-trimethylbenzoylphosphinate. However, this deficiency is cured by Lin and Murphy.
The teachings of Lin are described above. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘195 and Lin and utilize PEG dithiol as the crosslinker. One skilled in the art would have been motivated PEG dithiol as it is a crosslinker known to be used with PEG norbornene as taught by Lin. Since copending ‘636 claims a linker which can be utilized with PEG norbornene there is a reasonable expectation of success.
The teachings of Murphy are described above. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘195 and Murphy and add lithium phenyl-2,4,6-trimethylbenzoylphosphinate as an initiator in order to have the ability to induce polymerization and decrease the polymerization rate as taught by Murphy.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicants’ remarks filed February 3, 2026 have been fully considered and are found to be mostly unpersuasive in view of the amendments to the claims.
Applicants note the amendment to the claims.
II. Claim Rejections under 35 USC Sec. 102
Applicants argue that Lin does not teach or suggest a microcapsule comprising a core and a polymeric shell enclosing the core, the core comprising a cell. Applicants assert that Lin’s single layer and multilayer hydrogels are not described as core-shell microcapsules. Lin describes dual layer microgels in which a core microgel is formed and subsequently coated with an interfacial gel layer. Applicants assert that the core in Lin is a microgel, not a cell. Lin requires reacting the cells with PEGSH and then reacting the PEG-SH-cell with macromer and crosslinking agent
Applicants argue that Lin’s coating mechanism is surface-mediated and conditional as opposed to inherent and the hydrogel layer forms only when the surface has been chemically modified.
Response
Applicants’ arguments that Lin does not teach or suggest a microcapsule comprising a core and a polymeric shell enclosing the core, the core comprising a cell are not found to be persuasive. The core in Lin contains a cell. There is a core which contains a cell and there is a polymer shell surrounding it.
Nowhere in the language of the claims is there a prohibition or limitation to how the microcapsule comprising a core and polymeric core enclosing the core, the core comprising a cell, is formed. Lin teaches reacting the cells with PEGSH and then reacting the PEG-SH-cell with macromer and crosslinking agent to form the shell structure.
The claim is drafted with the open ended transitional phrase of comprising, so the presence of additional elements, as long as the recited cell is present (which it is in this instance) is not prohibited. Respectfully, Applicants are requiring limitations that the express language of the claims simply does not recite.
However, in light of the amendments to the claims the rejection has been withdrawn above and a new rejection has been applied above.
III. Obviousness Type Double Patenting Rejections
With respect to the obviousness type double patenting rejections, Applicants request that the rejections be held in abeyance.
Response
Applicants request to hold the double patenting rejection in abeyance until there is an indication of allowability of claims is noted, however, Applicant is reminded that a request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see MPEP 37 CFR 1.111(b) and 714.02). Thus, the double patenting rejection is maintained for reasons of record as no action regarding this rejection has been taken by applicants at this time.
In light of the amendments to the claims the obviousness-type double patenting rejection have been withdrawn above and new obviousness-type double patenting rejections have been applied above.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH CHICKOS whose telephone number is (571)270-3884. The examiner can normally be reached on M-F 9-6.
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/SARAH CHICKOS/
Examiner, Art Unit 1619
/SARAH ALAWADI/ Primary Examiner, Art Unit 1619