DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 06/23/2026 is acknowledged.
Status of Application
Applicant has elected Group I in response to restriction requirement and for the examination.
Due to restriction, based on election of Group I, claims 32 and 37 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 18-36 are pending.
Claims 18-31 and 33-36 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Claims 18-22, 26-31, 33-36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (An Interpenetrating Alginate/Gelatin Network for Three-Dimensional (3D) Cell Cultures and Organ Bioprinting).
Rejection:
Chen et al. teaches a method of making gelatin/alginate hydrogels comprising combining alginate and gelatin in phosphate buffer saline (PBS) to form a well-mixed solution, and then contacted with a 10% w/v transglutaminase solution to crosslink the gelatin and contacted with a 2%w/v calcium chloride solution for ionic crosslinking the alginate. Additional amounts of the transglutaminase and calcium chloride solutions are added when the polymer concentrations were increased to fully ensure crosslinking (Page 14 section 4.2, Page 15 section 4.6).
Chen et al. teaches that the double crosslinking model such as using calcium ions to crosslink the alginate and transglutaminase to crosslink gelatin, improves the properties of the alginate/gelatin hydrogels like the water holding capacity and structural integrity making it desirable for a range of biomedical applications like cell cultures and organ bioprinting (abstract). The amount of gelatin and alginate falls within the claimed range (i.e. gelatin 2w/v% and 5w/v%; alginate is from about 0.5-2.5%w/v, Table 1).
Chen et al. exemplifies making the double crosslinked hydrogel including with suspension of human neuroblastoma cells (SH-SY5Y) in an alginate/gelatin solution (0.75%w/v alginate and 2%w/v gelatin, hydrosols), then a 10% w/v transglutaminase solution was used to crosslink the gelatin in the hydrosols at 37oC for 6 hours and a 2%w/v calcium chloride solution to crosslink the alginate; there was 1 ml of alginate/gelatin solution in each well of a 12 well plate (shaped/molded) where the samples were vibrated to suspend the cells evenly and the crosslinking agents covered the hydrosols (immersed, when both transglutaminase and calcium chloride are added and covering the hydrosol/hydrogels they combine to form one solution, Page 15 section 4.6, see full document specifically areas cited).
All the critical elements are taught by the cited reference and thus the claims are anticipated.
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.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (An Interpenetrating Alginate/Gelatin Network for Three-Dimensional (3D) Cell Cultures and Organ Bioprinting) as applied to claims 18-22, 26-31, 33-36 above, in view of MacQueen et al. (U.S. Pat. Pub. 2020/0330644).
Rejection:
The teachings of Chen et al. are addressed above.
Chen et al. does not expressly teach the inclusion of fibrinogen and thrombin, but does teach the method of making a double crosslinked gelatin/alginate hydrogel with cells useful as a bioink and a 3D support/organ constructs.
MacQueen et al. teaches that bioinks/hydrogels/3D tissue scaffolds are known to incorporate biogenic polymers to promote cell attachment and 3D tissue culture and structural/functional support [132] including fibrinogen and thrombin ([134] line 11-12).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate fibrinogen and thrombin as suggested by MacQueen et al. and produce the claimed invention, as it is prima facie obvious to incorporate known polymers for their known use in bioinks/hydrogels/3D tissue scaffolds with a reasonable expectation of success. It is also prima facie obvious to incorporate them at any step (i.e. fibrinogen in hydrogel/hydrosol, thrombin with crosslinker) absent evidence of criticality for the recited step.
Claims 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (An Interpenetrating Alginate/Gelatin Network for Three-Dimensional (3D) Cell Cultures and Organ Bioprinting) in view of MacQueen et al. (U.S. Pat. Pub. 2020/0330644) as applied to claim 23 above, further in view of Marquette et al. (U.S. Pat. Pub. 2019/0002836).
Rejection:
The teaching of Chen et al. in view of MacQueen et al. are addressed above, including 10% transglutaminase and 2% calcium chloride.
Chen et al. in view of MacQueen et al. does not expressly recited the amount of fibrinogen or thrombin, but does teach their inclusion.
Marquette et al. teaches that fibrinogen and thrombin are useful in bioinks with fibrinogen of 0.2% preferably the minimum amount of 0.3% as if there is not enough the cells will not adhere to the bio-ink and spread, and if too much fibrinogen it will be too hard to use; and have enough thrombin at a concentration for the fibrinogen transform to fibrin [78] such as 10 U/ml-30U/ml [34].
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate fibrinogen at 0.2% preferably the minimum amount of 0.3% as suggested by Marquette et al. and produce the claimed invention, as it is prima facie obvious to incorporate the fibrinogen at its known range which overlaps the claimed range wherein even a slight overlap establishes a prima facie case of obviousness as it is obvious to optimize within the range to attain the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality.
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 18, 20-22, 27-31, 33-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49-54 of copending Application No. 18/029290 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are directed to a method of making a hydrogel 3 dimensional bod implant comprising preparing a hydrogel with gelatin and alginate, shaping the hydrogel, and crosslinking the hydrogel with at least one divalent cation and transglutaminase wherein the copending claims fall within the breath instantly claimed. As there is no heating temperature recited, the method is implicitly at room temperature (25oC) falling within the claimed range.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 19, 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49-54 of copending Application No. 18/029290 (reference application) as applied to claims 18, 20-21, 27-31, 33-36 above, in view of Chen et al. (An Interpenetrating Alginate/Gelatin Network for Three-Dimensional (3D) Cell Cultures and Organ Bioprinting).
The teaching of the copending claims are addressed above.
The copending claims do not recited immersion of the hydrogel with the crosslinkers, or the amount of alginate/gelatin.
Chen et al. takes human neuroblastoma cells (SH-SY5Y) where suspended in alginate (0.75%w/v)/gelatin (2%w/v) solutions (hydrosols), then the a 10% w/v transglutaminase solution was used to crosslink the gelatin in the hydrosols at 37oC for 6 hours and contacted with a 2%w/v calcium chloride solution to crosslink the alginate; there was 1 ml of alginate/gelatin solution in each well of a 12 well plate (shaped/molded) where the samples were vibrated to suspend the cells evenly and the crosslinking agents covered the hydrosols (immersed, when both transglutaminase and calcium chloride are added and covering the hydrosol/hydrogels they combine to form one solution, Page 15 section 4.6).
Wherein it would be obvious to one of skill in the art to add the crosslinkers on top of hydrogel (immerse) and the known amounts of gelatin and alginate and known amounts of the crosslinkers (transglutaminase/calcium) as suggested by Chen et al. and produce the claimed invention as it is prima facie obvious to add the crosslinkers at known means and amounts and the known amounts of gelatin/alginate with a reasonable expectation of success..
Claims 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49-54 of copending Application No. 18/029290 (reference application) as applied to claims 18, 20-21, 27-31, 33-36 above,
in view of Marquette et al. (U.S. Pat. Pub. 2019/0002836).
The teaching of copending claims are addressed above.
The copending claims do not recite the amount of fibrinogen or the inclusion of thrombin.
Marquette et al. teaches that fibrinogen and thrombin are useful in bioinks with fibrinogen of 0.2% preferably the minimum amount of 0.3% as if there is not enough the cells will not adhere to the bio-ink and spread, and if too much fibrinogen it will be too hard to use; and have enough thrombin at a concentration for the fibrinogen transform to fibrin [78] such as 10 U/ml-30U/ml [34].
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate fibrinogen at 0.2% preferably the minimum amount of 0.3% and incorporate thrombin as suggested by Marquette et al. and produce the claimed invention, as it is prima facie obvious to incorporate the fibrinogen at its known range which overlaps the claimed range wherein even a slight overlap establishes a prima facie case of obviousness as it is prima facie obvious to optimize within the range to attain the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality. It is also prima facie obvious to incorporate the thrombin as an adequate amount is needed to convert the fibrinogen to fibrin with a reasonable expectation of success.
Claim 25 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49-54 of copending Application No. 18/029290 (reference application) in view of Marquette et al. (U.S. Pat. Pub. 2019/0002836) as applied to claims 23-24 above, further in view of Chen et al. (An Interpenetrating Alginate/Gelatin Network for Three-Dimensional (3D) Cell Cultures and Organ Bioprinting).
The teaching of the copending claims in view of Marquette et al. are addressed above.
The copending claims in view of Marquette et al. does not address the amount of the divalent ion or amount of transglutaminase but does teach its inclusion.
Chen et al. teaches the inclusion of 10% transglutaminase and 2% calcium chloride for alginate/gelatin hydrogels for crosslinking for improved properties.
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the transglutaminase and calcium chloride (divalent cation) at 10%w/v and 2%w/v respectively as suggested by Chen et al. and produce the claimed invention, as it is prima facie obvious to incorporate the transglutaminase and calcium at its known values with a reasonable expectation of success.
Conclusion
Claims 18-31 and 33-36 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613
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