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 .
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/01/2026 has been entered.
Claims 1, 4-6, 8-11, and 14 have been amended.
Claims 1-14 are pending and under examination.
2. The objections to claims 1, 11, and 14 are withdrawn in response to the amendments filed on 06/01/2026.
The written description and obviousness-type rejections are withdrawn in response to applicant’s arguments.
New grounds of rejection are set forth below.
Claim Objections
3. Claims 4 and 8 are objected to because of the recitation “having a function of NDST2”. Correction to “having NDST2 activity” is suggested.
4. Claims 5 and 9 are objected to because of the recitation “having a function of Hs3st1”. Correction to “having Hs3st1 activity” is suggested.
5. Claims 6 and 10 are objected to because of the recitation “has a function of the extracellular domain of SDC”. Correction to “has the activity of the SDC extracellular domain” is suggested.
Claim Rejections - 35 USC § 103
6. Claims 1-5, 7-9, and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Yayon, in view of Baik et al. (Metabolic Engineering, 2012, 14: 81-90).
Yayon teaches a recombinant CHO cell comprising a gene encoding the syndecan ectodomain (extracellular domain); the soluble syndecan ectodomain is post-translationally modified with heparan sulfate (HS), carries and release the HS into the culture medium (claims 11, 13, and 14) (see p. 3, lines 1-4; p. 4, lines 18-21; p. 15, lines 1-9; p. 16, line 30 through p 17, line 9; claims 1, 4, 9-12; 14).
Yayon do not teach transfecting the CHO cells with plasmids encoding the mouse Hs3st1 and the human NDST2 and using the resultant recombinant CHO cell to produce heparin/HS (a heparin-like substance; see the specification, [0018]) (claims 1-3 and 12). Baik et al. teach that heparin is the most widely used pharmaceutical to control blood coagulation; Baik et al. teach that CHO cells express HS; genetically engineering the CHO cells to express the mouse Hs3st1 and the human NDST2 results in recombinant cells capable of also producing heparin (claim 7). Baik et al. teach that the genetically engineered CHO cells secrete heparin/HS in the culture medium, supporting the hypothesis that the HS/heparin chains use syndecan for targeting the heparin/HS on the cell surface. Baik et al. teach that overexpressing syndecan would increase heparin secretion (as the syndecan ectodomain carrying heparin/HS is released into the culture medium via the action of proteases), eliminating the need for cell lysis and greatly simplifying the heparin purification process (see Abstract; p. 82; p. 83, column 1, second full paragraph; p. 84, column 1; p. 85, column 2, first paragraph; paragraph bridging p. 85 and 86; p. 87, column 2; p. 89, column 1). Based on the combined teachings of Yayon and Baik et al., one of skill in the art would have reasonably concluded that Yayon’ CHO cells overexpressing the syndecan ectodomain would be suitable to be genetically engineered for increased production of secreted heparin. One of skill in the art would have found obvious to modify Yayon’ CHO cells by transfecting them with plasmids encoding the mouse Hs3st1 and the human NDST2 as taught by Baik et al., to achieve the predictable result of obtaining increased heparin secretion into the culture medium and simplify heparin purification process. Since the specification discloses that SEQ ID NOs: 4 and 5 used to obtain the claimed recombinant cell are the NDST2- and Hs3st1-encoding nucleic acids of Baik et al. (see [0078]), one of skill in the art would have used SEQ ID NOs: 2-5 (claims 4, 5, and 7-9).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
7. Claims 1-5, 7-9, and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Baik et al. (Metabolic Engineering, 2012, 14: 81-90), in view of Yayon
(WO 01/40267).
Baik et al. teach (1) a recombinant CHO cell obtained by transfecting the CHO cell with plasmids encoding the mouse Hs3st1 and the human NDST2; and (2) using the recombinant CHO cell to produce heparin/HS (claims 1-3, 7, 12, and 13) (see Abstract; p. 83, column 1, second full paragraph; p. 84, column 1; p. 85, column 2, first paragraph; p. 89, column 1). As defined by the specification, the heparin-like substance is a heparin/HS mixture (see [0018]).
Baik et al. do not teach that the recombinant CHO cell comprises a gene encoding the extracellular domain of syndecan (claims 1, 11, and 14). However, Baik et al. teach that the genetically engineered CHO cells secrete heparin/HS in the culture medium, supporting the hypothesis that the HS/heparin chains use the syndecan for targeting the heparin/HS on the cell surface. Baik et al. teach that overexpressing syndecan would increase heparin secretion (as the syndecan ectodomain carrying heparin/HS is released into the culture medium via the action of proteases), eliminating the need for cell lysis and greatly simplifying heparin purification (see Abstract; p. 82; p. 83, column 1, second full paragraph; p. 84, column 1; p. 85, column 2, first paragraph; paragraph bridging p. 85 and 86; p. 87, column 2; p. 89, column 1). Furthermore, Yayon teaches that cells (including CHO cels) genetically engineered to express the syndecan ectodomain accumulate together with the associated HS into the culture medium (see p. 3, lines 1-4; p. 4, lines 18-21; p. 15, lines 1-9; p. 16, line 30 through p. 17, line 9). Based on the combined teachings of Baik et al. and Yayon, one of skill in the art would have reasonably concluded that overexpressing the syndecan ectodomain could be used to increase the secretion of heparin/HS into the culture medium and simplify the purification process. One of skill in the art would have found obvious to modify the recombinant CHO cell by transfecting it with an expression vector encoding the syndecan ectodomain to achieve the predictable result of simplifying the purification process.
Since the specification discloses that SEQ ID NOs: 4 and 5 used to obtain the claimed recombinant cell are the NDST2- and Hs3st1-encoding nucleic acids of Baik et al. (see [0078]), Baik et al. teach SEQ ID NOs: 2-5 (claims 4, 5, 8 and 9).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
8. Claims 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Yayon taken with Baik et al., in further view of Daisuke et al. (WO 15/076282).
The English language translation of the WO 15/076282 document is U.S. Patent No. 10,370,450; the passages indicating the teachings of the WO 15/076282 document are based on its English language translation, i.e., the U.S. Patent No. 10,370,450.
The teachings of Yayon and Baik et al. are applied as above for claims 1-5, 7-9, and 11-14. Yayon and Baik et al. do not specifically teach that the syndecan ectodomain domain is set forth by SEQ ID NO: 1, which is encoded by SEQ ID NO: 6 (claims 6 and 10). However, it is noted that there is no evidence of record indicating that specifically using SEQ ID NO: 1 leads to unexpected results. One of skill in the art would have found obvious to use any syndecan ectodomain to achieve the predictable result of achieving increased secretion of bioengineered heparin. Furthermore, Daisuke et al. teach the extracellular domain of syndecan-1 set forth by SEQ ID NO: 10 and encoded by SEQ ID NO: 9 (see column 2, lines 34-52). These sequences have a length of 250 amino acids and 750 nucleotides, respectively. As evidenced by the Sequence Alignments of record, the amino acids 1-229 of SEQ ID NO: 10 and 1-687 of SEQ ID NO: 9 are identical to the claimed SEQ ID NO: 1 and SEQ ID NO: 6, respectively. Using these sequences to obtain the recombinant CHO cell expressing the extracellular domain of syndecan would have been obvious to one of skill in the art to achieve the predictable result of simplifying the purification process.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
9. Claims 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Baik et al. taken with Yayon, in further view of Daisuke et al. (WO 15/076282).
The English language translation of the WO 15/076282 document is U.S. Patent No. 10,370,450; the passages indicating the teachings of the WO 15/076282 document are based on its English language translation, i.e., the U.S. Patent No. 10,370,450.
The teachings of Baik et al. and Yayon are applied as above for claims 1-5, 7-9, and 11-14. Baik et al. and Yayon do not specifically teach that the syndecan ectodomain is set forth by SEQ ID NO: 1, which is encoded by SEQ ID NO: 6 (claims 6 and 10). However, it is noted that there is no evidence of record indicating that specifically using SEQ ID NO: 1 leads to unexpected results. One of skill in the art would have found obvious to use any syndecan ectodomain to achieve the predictable result of achieving increased secretion of bioengineered heparin. Furthermore, Daisuke et al. teach the extracellular domain of syndecan-1 set forth by SEQ ID NO: 10 and encoded by SEQ ID NO: 9 (see column 2, lines 34-52). These sequences have a length of 250 amino acids and 750 nucleotides, respectively. As evidenced by the attached Sequence Alignments, the amino acids 1-229 of SEQ ID NO: 10 and 1-687 of SEQ ID NO: 9 are identical to the claimed SEQ ID NO: 1 and SEQ ID NO: 6, respectively. Using these sequences to obtain the recombinant CHO cell expressing the extracellular domain of syndecan would have been obvious to one of skill in the art to achieve the predictable result of simplifying the purification process.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
10. None of the arguments pertains to the new rejections.
11. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633
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