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 .
Priority
This application is a 371 of PCT/US2020/048243 filed on 08/27/2020. PCT/US2020/048243 has PRO 63/005,146 filed on 04/03/2020. PCT/US2020/048243 has PRO 62/892,477 filed on 08/27/2019.
Election/Restrictions
Claims 84-86, 113, 126, 140 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II and III. Election was made without traverse in the reply filed on 05/13/2025. Applicant’s election without traverse of Group I drawn to a method of producing, in the reply filed on 05/13/2025 is acknowledged.
Claim Status
Claims 1-3, 5-13, 17, 19, 84-86, 113, 126, 140 are pending. Claims 84-86, 113, 126, 140 are withdrawn. Claims 1, 6, 10, 13 are amended. Claims 1-3, 5-13, 17, and 19 are being examined on the merits in this office action.
Claim Objections and Rejections - Withdrawn
The objection of claims 10 and 13 is withdrawn in view of the amended claims.
The rejection of claims 1-3, 6, 8-10, 12-13 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gasimli et al. (Glycobiology, Volume 24, 3: 2014, Pages 272–280) is withdrawn in view of the claim amendments.
Claim Rejections - 35 USC § 102 - Maintained
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 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 1-3, 5-13 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Glass et al. (WO2018112434A1* – hereinafter “Glass”)*.
Regarding claim 1, Glass teaches a method of preparation of a substantially pure heparin or hyper- sulfated heparan sulfate comprising growing genetically modified cell line using an appropriate growth media and isolating the growth media from the cells by centrifugation [0008-0009]. Glass teaches that the cell line includes mast cells [0007, 0033, 0061, 0137]. Glass further teaches cell lines including KU812 [0053] which is a basophil neoplastic cell line. Glass teaches the instant method and teaches that the cell line expresses Hs3st1 [0015], Hs6st1 and sulf2 [0014, 0060]. The disclosure anticipates claim 1.
Regarding claim 2, Glass teaches that the cell line includes mast cells [0007, 0033, 0061, 0137] and that the mast cells include a P815 cell, MC/9 cell [0053].
Regarding claim 3, Glass teaches that the cell line is deficient in chondroitin sulfate synthase 1 (ChSyl) [0007].
Regarding claim 5, Glass teaches that the cell line is deficient in heparanase (Hpse), beta-glucuronidase (Gusb) [0060].
Regarding claims 6, 8, and 11-12, Glass teaches that the cell is transgenic for one or more genes that encode a proteoglycan core protein, such as any membrane proteoglycan (e.g., a glypican, a syndecan, or any secreted proteoglycan (e.g. serglycin, perlecan, collagen XVIII, or agrin, glypican 1 (Gpcl), glypican 2 (Gpc2), lypican 3 (Gpc3), glypican 4 (Gpc4), glypican 5 (Gpc5), glypican 6 (Gpc6), syndecan 1 (Sdcl), syndecan 2 (Sdc2), syndecan 3 (Sdc3), syndecan 4 (Sdc4), betaglycan [0060].
Regarding claim 7, Glass teaches that the protease comprises trypsin and chymotrypsin [0069].
Regarding claim 9, Glass teaches that the cell is transgenic for one or more genes that encode a proteoglycan core protein, such as any membrane proteoglycan (e.g., a glypican, a syndecan, or any secreted proteoglycan (e.g. serglycin, perlecan, collagen XVIII, or agrin, glypican 1 (Gpcl), glypican 2 (Gpc2), lypican 3 (Gpc3), glypican 4 (Gpc4), glypican 5 (Gpc5), glypican 6 (Gpc6), syndecan 1 (Sdcl), syndecan 2 (Sdc2), syndecan 3 (Sdc3), syndecan 4 (Sdc4), betaglycan [0060]. Glass further teaches that the cell is a mouse cell, a rat cell, a non-human primate cell, or a human cell [0053].
Regarding claim 10, Glass teaches that proteins are further modified (i.e., glycosylated) in the cell with various diverse GAGs thereby creating proteoglycans [0029].
Regarding claim 13, Glass teaches that the genetically modified cell line overexpresses Ndst1 and Ndst2 [0024-0025, 0162-0163].
Claim Rejections - 35 USC § 103 - Maintained
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.
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 17 and 19 remain rejected under 35 U.S.C. 103 as being unpatentable over Glass et al. (WO2018112434A1* – hereinafter “Glass”)* as applied to claim 1 above, and further in view of Bashkin et al. *(Blood, Vol 75, No 11 (June 1). 1990: pp 2204-2212)*.
The teachings of Glass are disclosed above and incorporated herein by reference.
Glass does not teach degranulating the cell line as recited in claim 17.
Bashkin teaches Caz+-ionophore (A23187) and IgE-mediated degranulation of mouse mast cell (BMMC) and that the cultured mast cells were incubated for 45 minutes at 37ºC with the calcium-ionophore A23187 (page 2205, left col., 3rd paragraph, line 1015).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Glass and degranulate the cell line as taught by Bashkin so as to release the heparin. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in degranulating the mast cell line using Caz+-ionophore (A23187) and IgE-mediated degranulation as taught by Bashkin so as to release the heparin.
Regarding claims 17 and 19, Bashkin teaches Caz+-ionophore (A23187) and IgE-mediated degranulation of mouse mast cell (BMMC) and that the cultured mast cells were incubated for 45 minutes at 37OC with the calcium-ionophore A23187 (page 2205, left col., 3rd paragraph, line 1015).
Response to Arguments
Applicant's arguments filed10/01/2025 have been fully considered but they are not persuasive.
Applicant argues that the cited references do not teach wherein the genetically modified cell line overexpresses Heparan sulfate-glucosamine 3-0- sulfotransferase 1 (Hs3stl), Heparan-sulfate 6-0-sulfotransferase 1 (Hs6stl), and sulfatase 2 (Sulf2).
Examiner notes the cited reference Glass et al. teach producing the instant heparin or heparan sulfate and teach using the instant mastocytoma cell line and further teach that the cell line expresses Hs3st1, Hs6st1 or Sulf2. The arguments are unpersuasive.
Double Patenting - Maintained
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, 5-6, 13, 17, 19 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 11, and 13-17 of copending Application No. 18/575,016. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the copending application recite a method a heparin or heparan sulfate, the method comprising culturing a genetically modified mastocytoma cell line; and isolating the heparin or heparan sulfate from the cell line, wherein the genetically modified cell line overexpresses one or more of heparan sulfate-glucosamine 3- sulfotransferae 1 (Hs3stl), heparan sulfate 6-0-sulfotransferase 1 (Hs6stl), heparan sulfate 6-0- sulfotransferase 2 (Hs6st2), and N-deacetylase N-sulfotransferase 2 (Ndst2), and Sulf-2.2 (claim 1).
The instant claims recite a method of producing a heparin or a heparan sulfate, the method comprising culturing a genetically modified cell line comprising at least one of a mastocytoma cell line and a basophil neoplastic cell line; wherein the genetically modified cell line overexpresses Heparan sulfate-glucosamine 3-0-sulfotransferase 1 (Hs3stl), Heparan-sulfate 6- 0-sulfotransferase 1 (Hs6stl), and sulfatase 2 (Sulf2); and isolating the heparin or heparan sulfate from the genetically modified cell line (claim 1).
The claims of the copending application anticipate the instant claims.
Regarding claim 2, the claims of the copending application recite wherein the mastocytoma cell line is selected from the group consisting of MST cells, P815 cells, MC/9 cells, SI/S14 cells, 10P2 cells, 11PO-1 cells, and 1OP12 cells (claim 3).
Regarding claim 3, the claims of the copending application recite wherein the genetically modified cell line is deficient for one or more of chondroitin sulfate N-acetylgalactosaminyltransferase 1 (Csgalnactl), chondroitin sulfate N- acetylgalactosaminyltransferase 2 (Csgalnact2), chondroitin sulfate synthase 1 (Chsyl), and Heparan sulphate 2-0-sulfotransferase (Hs2st) (claim 2).
Regarding claim 5, the claims of the copending application recite wherein the genetically modified cell line is deficient for a heparan sulfate catabolic enzyme (claim 4).
Regarding claim 6, and 13 the claims of the copending application recite wherein the genetically modified cell line overexpresses one or more of heparan sulfate-glucosamine 3- sulfotransferae 1 (Hs3stl), heparan sulfate 6-0-sulfotransferase 1 (Hs6stl), heparan sulfate 6-0- sulfotransferase 2 (Hs6st2), and N-deacetylase N-sulfotransferase 2 (Ndst2), and Sulf-2.2 (claim 1, 11).
Regarding claim 17, the claims of the copending application recite wherein the method comprises degranulating the cell line (claim 5), wherein degranulating the cell line comprises a method selected from the group consisting of Antigen -IgE induced Fec
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RI aggregation on the degranulating cell surface, contacting the cell line to a degranulating agent, altering the culture temperature, altering the culture medium pH, altering the culture medium salt concentration, and agitation (claim 6).
Regarding claim 19, the claims of the copending application recite wherein the degranulating agent is selected from the group consisting of calcium ionophore A23187, compound 48/80, tetradecanoyl phorbol acetate (TPA), and substance P (claim 7).
Claims 1-3, 5-6, 8, 11-13, remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 59, 76, 99-100 of copending Application No. 18/064,181 in view of Glass et al. (WO2018112434A1 – hereinafter “Glass”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the copending application recite a method of preparation of a substantially pure glycosaminoglycan selected from a group consisting of heparan sulfate comprising growing a cell deficient or transgenic in one or more genes recited in Tables 1, 2, 4 or 5, using an appropriate growth media, (b) isolating the growth media from the cells by centrifugation (claim 59).
The instant claims recite a method of producing a heparin or a heparan sulfate, the method comprising culturing a genetically modified cell line comprising at least one of a mastocytoma cell line and a basophil neoplastic cell line; wherein the genetically modified cell line overexpresses Heparan sulfate-glucosamine 3-0-sulfotransferase 1 (Hs3stl), Heparan-sulfate 6- 0-sulfotransferase 1 (Hs6stl), and sulfatase 2 (Sulf2);and isolating the heparin or heparan sulfate from the genetically modified cell line (claim 1).
The difference between the claims of the copending application and the instant claims is that the claims of the copending application do not recite that the cell is a mast cell.
However, a method of preparing heparan sulfate comprising growing a cell is known in the art as taught by Glass et al. (WO2018112434A1 – hereinafter “Glass”)
Glass teaches a method of preparation of a substantially pure heparin or hyper- sulfated heparan sulfate comprising growing genetically modified cell line using an appropriate growth media and isolating the growth media from the cells by centrifugation [0008-0009]. Glass teaches that the cell line includes mast cells [0007, 0033, 0061, 0137]. Glass further teaches cell lines including KU812 [0053] which is a basophil neoplastic cell line. Glass teaches the instant method and teaches that the cell line expresses Hs3st1 [0015], Hs6st1 and sulf2 [0014, 0060].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the copending application and use mast cells to prepare the heparan sulfate thus arriving to the instant invention. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in modifying the claims of the copending application and use mast cells to produce the heparan sulfate thus arriving to the instant claim.
The claims of the copending application render obvious the instant claims.
Regarding claim 2, Glass teaches using mast cells to produce heparin [0007, 0033, 0061, 0137]. It would have been obvious to modify the copending claims and use mast cells to produce the heparan sulfate thus arriving to the instant claims.
Regarding claims 3, 5, the claims of the copending application recite wherein the cell is deficient in one or more of chondroitin sulfate synthase 1 (ChSy), Chondroitin Sulfate N-Acetylgalactosaminyltransferase 2 (CSGalNAcT2), Chondroitin Polymerizing Factor (ChPF), heparan sulfate 2-0- sulphotransferase (HS2ST), glucuronic acid epimerase (GLCE), heparan sulfate N- deacetylase/sulfotransferase-1 (HSNDST1), heparan sulfate N-deacetylase/sulfotransferase-2 (HSNDST2), Sulfatase 1 (Sulfl), Sulfatase (Sulf2), Beta-glucuronidase (GUSB), Galactosamine-6 sulfatase (GALNS), Alpha-L-iduronidase (IDUA) (claim 99).
Regarding claims 6, 8, 11-13, the claims of the copending application recite wherein the cell is transgenic for one or more of heparan sulfate 2-0-sulphotransferase (HS2ST), glucuronic acid epimerase (GLCE), heparan sulfate N- deacetylase/sulfotransferase-1 (HSNDST1), heparan sulfate N-deacetylase/sulfotransferase-2 (HSNDST2), Heparanase (HPSE), Glypican 1 (GPC1), Glypican 2 (GPC2), Glypican 3 (GPC3), Glypican 4 (GPC4), Glypican 5 (GPC5), Glypican 6 (GPC6), Syndecan 1 (SDC1), Syndecan2 (SDC2), Syndecan3 (SDC3), Syndecan 4 (SDC4), Betaglycan (BGCAN/TGFBR3), CD44V3 (CD44V3), Neuropillin 1 (NRP1), Serglycin (SRGN), Perlecan (PLC), Agrin (AGRN) (claim 100).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 10/01/2025 have been fully considered but they are not persuasive.
Applicant argues that claim 1 and dependents therefrom are patentably distinct with respect to the asserted claims of U.S. Application Nos. 18/575,016 and 18/064,181.
Examiner disagrees and notes that the instant claims are not patentably distinct from copending applications 18/575,016 and 18/064,181 because as indicated in the rejection above, the copending applications recite all the limitations of the claimed invention or render obvious the claimed invention. The arguments are unpersuasive.
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 Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654