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 the Application
1. Claims 1-17 are pending and subject to examination on the merits. Claims 12-17 are withdrawn from consideration as being drawn to non-elected subject matter. Claims 1-11 are currently under examination.
Priority
2. Acknowledgment is made for the Applicant’s claim for domestic priority based on the US provisional application PRO 63/216,495 filed 29 June 2021.
Election/Restrictions
3. Applicant’s election without traverse of Group I (Claims 1-11) in the reply filed on 27 July 2026 is acknowledged.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on 27 July 2026 has been considered by the examiner. See initialed and signed PTO/SB/08’s.
Drawings
5. The drawings are objected to because Fig 1A, Fig. S1A, Fig. S1B, Fig. S1C, Fig. S1D, Fig. S1E, Fig. S2A, Fig. S2B, Fig. 4A, Fig. 5B, Fig. 5C, Fig. 7A, Fig. 7B have large letters either to the top right or even at the bottom of the page that are either present or partially occluded. Delete these large letters completely. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
6. The use of the term GlutaMAX™ (paragraph 00103), RNeasy™ (paragraph 00105), TruSeq™ (paragraph 00105), HiSeq™ 4000 (paragraph 00105), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
7. Claims 4-11 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot dependent from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claim Interpretation
8. For examination, claims 4-11 will be examined as being dependent on claim 1 only, since the claim language recites “any one of claims…” (directly applicable to claims 4-5 and 8-11).
Claim Rejections - 35 USC § 102
9. 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.
10. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
11. Claims 1-10 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Glass et al (Glass et al., 2021, WO 2021/041711 A1—cited on the IDS dated 27 July 2026). Regarding claims 1 and 3, drawn to a method of producing heparin or heparan sulfate, comprising culturing a genetically modified mastocytoma cell line, wherein said line is a MST cell line (claim 3), 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-sulfotransferase (Hs3st1), heparan sulfate 6-O-sulfotransferase 1 (Hs6st1), heparan sulfate 6-O-sulfotransferase 2 (Hs6st2), N-deacetylase N-sulfotransferase 2 (Ndst2), and Sulf-2, Glass et al. teaches methods of producing heparin and heparan sulfate from modified MST cells, further comprising culturing a genetically modified cell line and isolating the heparin or heparan sulfate from the cell line (abstract). Specifically, Glass et al. teaches the overexpression of one or more of Hs3st1, Hs6st1, Hs6st2, Ndst2, or Sulf2 (paragraph 0004). Regarding claim 2, wherein the genetically modified cell line is deficient for one or more of chondroitin sulfate N-acetylgalactosaminyltransferase 1 (Csgalnact 1), chondroitin sulfate N-acetylgalactosaminyltranferase 2 (Csgalnact2), chondroitin sulfate synthase 1 (Chsy 1), and Heparan sulphate 2-O-sulfotransferase (Hs2st), Glass et al. teaches the genetically modified cells being deficient for one or more of CHSY 1, CCSGALNACT2, CSGALNACT1, HS2ST, and GLCE (paragraph 0007). Regarding claim 4, drawn to the utilization of a genetically modified cell line deficient for a heparan sulfate catabolic enzyme, Glass et al. teaches the utilization of a genetically modified cell line deficient in a heparan sulfate catabolic enzyme (paragraph 0004). Regarding claims 5-7, drawn to degranulating the cell line (claim 5) comprising a method of Antigen-IgE induced FcεRI 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), and utilizing an agent selected from the group consisting of calcium ionophore A23187, compound 48/80, tetradecanoyl phorbol acetate (TPA), and substance P (claim 7), Glass et al. teaches the method comprising degranulating a cell, said method being selected from the group conssiiting of Antigen-IgE induced FcεRI 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, and utilizing an agent selected from the group consisting of calcium ionophore A23187, compound 48/80, tetradecanoyl phorbol acetate (TPA), and substance P (paragraph 0004). Regarding claim 8-9, drawn to the genetically modified cell line cultured in CDM4NS0 medium, supplemented with xylosides, Glass et al. teaches the genetically modified cell line cultured in CDM4NS0 medium, where said medium is supplemented with xylosides (paragraph 0004). Regarding claim 10, drawn to the genetically modified cell line cultured in suspension culture or in a hollow fiber bioreactor, Glass et al. teaches the genetically modified cell line cultured in suspension or in a hollow fiber bioreactor (paragraph 0004).
Claim Rejections - 35 USC § 103
12. 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.
13. Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Glass et al (Glass et al., 2021, WO 2021/041711 A1—cited on the IDS dated 27 July 2026) as applied to claims 1-10 above, and further in view of Glass et al., 2021, WO 2021/041711 A1—cite don the IDS dated 27 July 2026).
The teachings of Glass et al., as applicable to claims 1-10, are discussed above an incorporated into the instant rejection.
Regarding claim 11, drawn to the overexpression of Hs3st1, Hs6st1, and Sulf-2 and being deficient for Hs2st, Glass et al. teaches the overexpression of Hs3st1, Hs6st1, and Sulf-2 to produce heparin or a heparan sulfate in a genetically modified mastocytoma cell line (claims 1 and 16). Regarding the deficiency of Hs2st, Glass et al. teaches the production of heparin or a heparan sulfate in cell line deficient in Hs2st (claims 1 and 3).
Therefore, it 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 combine the teachings Glass et al. to utilize a cell line overexpressing Hs3st1, Hs6st1, and Sulf-2 and deficient in Hs2st to produce heparin or a heparan sulfate because Glass et al. teaches the modulation of said proteins to produce heparin or a heparan sulfate. One would be motivated to combine these teachings to arrive at the instant claims to produce a recombinant heparin to reduce the risk of HIT by engineering the molecular structure of cell-produced heparin, as taught by Glass et al (paragraph 0045). There would be reasonable expectation of success, yielding no surprising results when combining the teachings of knocking out Hs2st and simultaneously overexpressing Hs3st1, Hs6st1, and Sulf-2 to enhance the production of heparin or heparan sulfate in mastocytoma cells, since Glass et al. teaches the manipulation of the said gene products in the mastocytoma cell line.
Double Patenting
14. 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.
15. Claims 1-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 17, and 19 of copending Application No. 17/638,760 (reference application) and in view of Glass et al (Glass et al., 2021, WO 2021/041711 A1—cited on the IDS dated 27 July 2026). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims in their broadest are drawn to a method of producing heparin or heparan sulfate, comprising culturing a genetically modified mastocytoma cell line, wherein said line is a MST cell line (claim 3), 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-sulfotransferase (Hs3st1), heparan sulfate 6-O-sulfotransferase 1 (Hs6st1), heparan sulfate 6-O-sulfotransferase 2 (Hs6st2), N-deacetylase N-sulfotransferase 2 (Ndst2), and Sulf-2, and further wherein the genetically modified cell line is deficient for one or more of chondroitin sulfate N-acetylgalactosaminyltransferase 1 (Csgalnact 1), chondroitin sulfate N-acetylgalactosaminyltranferase 2 (Csgalnact2), chondroitin sulfate synthase 1 (Chsy 1), and Heparan sulphate 2-O-sulfotransferase (Hs2st) (claim 3). Claims 5-7 are drawn to a method of degranulating the cell line comprising a method selected from the group consisting of Antigen - IgE induced FcsRI 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, utilizing a degranulating agent selected from the group consisting of calcium ionophore A23187, compound 48/80, tetradecanoyl phorbol acetate (TPA), and substance P.
The ‘760 claims in their broadest are drawn to 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 simultaneously 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, wherein the mastocytoma cell line is a MST cell, and wherein the genetically modified cell line is deficient for one or more of chondroitin sulfate synthase 1 (CHSY1), chondroitin sulfate N- acetylgalactosaminyltransferase 2 (CSGALNACT2), chondroitin sulfate N- acetylgalactosaminyltransferase 1 (CSGALNACT1), Heparan sulfate 2-0-sulfotransferase (HS2ST), and heparan sulfate C5-epimerase (GLCE). Additionally, the ‘760 claims are drawn to a method of degranulating the cell line comprising a method selected from the group consisting of Antigen - IgE induced FcsRI 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, utilizing a degranulating agent selected from the group consisting of calcium ionophore A23187, compound 48/80, tetradecanoyl phorbol acetate (TPA), and substance P.
The ‘760 claims do not teach he genetically modified cell line cultured in CDM4NS0 medium, supplemented with xylosides, enetically modified cell line cultured in suspension culture or in a hollow fiber bioreactor, or the overexpression of Hs3st1, Hs6st1, and Sulf-2 and being deficient for Hs2st.
Regarding claims 8-9, drawn to the genetically modified cell line cultured in CDM4NS0 medium, supplemented with xylosides, Glass et al. teaches the genetically modified cell line cultured in CDM4NS0 medium, where said medium is supplemented with xylosides (paragraph 0004). Regarding claim 10, drawn to the genetically modified cell line cultured in suspension culture or in a hollow fiber bioreactor, Glass et al. teaches the genetically modified cell line cultured in suspension or in a hollow fiber bioreactor (paragraph 0004).
Regarding the deficiency of Hs2st, Glass et al. teaches the production of heparin or a heparan sulfate in cell line deficient in Hs2st (claims 1 and 3).
Therefore, it 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 combine the teachings of the ‘760 claims and Glass et al. to utilize a cell line overexpressing Hs3st1, Hs6st1, and Sulf-2 and deficient in Hs2st to produce heparin or a heparan sulfate because Glass et al. teaches the modulation of said proteins to produce heparin or a heparan sulfate. One would be motivated to combine these teachings to arrive at the instant claims to produce a recombinant heparin to reduce the risk of HIT by engineering the molecular structure of cell-produced heparin, as taught by Glass et al (paragraph 0045). There would be reasonable expectation of success, yielding no surprising results when combining the teachings Glass et al. with the ‘760 claims of knocking out Hs2st and simultaneously overexpressing Hs3st1, Hs6st1, and Sulf-2 to enhance the production of heparin or heparan sulfate in mastocytoma cells, since Glass et al. teaches the manipulation of the said gene products in the mastocytoma cell line.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
16. Claims 1-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44 and 54 of copending Application No. 19/670,992 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims in their broadest are drawn to a method of producing heparin or heparan sulfate, comprising culturing a genetically modified mastocytoma cell line, wherein said line is a MST cell line (claim 3), 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-sulfotransferase (Hs3st1), heparan sulfate 6-O-sulfotransferase 1 (Hs6st1), heparan sulfate 6-O-sulfotransferase 2 (Hs6st2), N-deacetylase N-sulfotransferase 2 (Ndst2), and Sulf-2, and further wherein the genetically modified cell line is deficient for one or more of chondroitin sulfate N-acetylgalactosaminyltransferase 1 (Csgalnact 1), chondroitin sulfate N-acetylgalactosaminyltranferase 2 (Csgalnact2), chondroitin sulfate synthase 1 (Chsy 1), and Heparan sulphate 2-O-sulfotransferase (Hs2st) (claim 3).
The ‘992 claims in their broadest are drawn to a method of utilizing a cell deficient in one or more of chondroitin sulfate N-acetylgalactosaminyltransferase 1 (Csgalnact 1), chondroitin sulfate N-acetylgalactosaminyltranferase 2 (Csgalnact2), chondroitin sulfate synthase 1 (Chsy 1) (and others) that is also transgenic in one or more of heparan sulfate-glucosamine 3-sulfotransferase (Hs3st1), heparan sulfate 6-O-sulfotransferase 1 (Hs6st1), heparan sulfate 6-O-sulfotransferase 2 (Hs6st2), N-deacetylase N-sulfotransferase 2 (Ndst2), and Sulf-2 (and many others), utilized in a method to produce heparin or heparan sulfate.
Regarding claims 8-9, drawn to the genetically modified cell line cultured in CDM4NS0 medium, supplemented with xylosides, Glass et al. teaches the genetically modified cell line cultured in CDM4NS0 medium, where said medium is supplemented with xylosides (paragraph 0004). Regarding claim 10, drawn to the genetically modified cell line cultured in suspension culture or in a hollow fiber bioreactor, Glass et al. teaches the genetically modified cell line cultured in suspension or in a hollow fiber bioreactor (paragraph 0004).
Regarding the deficiency of Hs2st, Glass et al. teaches the production of heparin or a heparan sulfate in cell line deficient in Hs2st (claims 1 and 3).
Therefore, it 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 combine the teachings of the ‘992 claims and Glass et al. to utilize a cell line overexpressing Hs3st1, Hs6st1, and Sulf-2 and deficient in Hs2st to produce heparin or a heparan sulfate because Glass et al. teaches the modulation of said proteins to produce heparin or a heparan sulfate. One would be motivated to combine these teachings to arrive at the instant claims to produce a recombinant heparin to reduce the risk of HIT by engineering the molecular structure of cell-produced heparin, as taught by Glass et al (paragraph 0045). There would be reasonable expectation of success, yielding no surprising results when combining the teachings Glass et al. with the ‘992 claims of knocking out Hs2st and simultaneously overexpressing Hs3st1, Hs6st1, and Sulf-2 to enhance the production of heparin or heparan sulfate in mastocytoma cells, since Glass et al. teaches the manipulation of the said gene products in the mastocytoma cell line.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
17. Claims 1-11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
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