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 .
Claims 1, 9, 24, 30, 46 and 50 have been amended. Claims 1-14, 24, 27, 30, 32-34, 36, 37 and 40-50 are pending and under consideration.
The replacement drawings, substitute specification and the sequence listing of 12/05/2025 have been entered.
Claim 50 is objected to because of the following informalities: the claim has an extraneous “-” preceding “and I361T”. Appropriate correction is required.
The rejection of claim 9 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in light of applicant’s amendment.
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.
The rejection of claims 1-14, 24, 27, 30, 32, 34, 36, 37, and 40-49 on the ground of nonstatutory double patenting as being unpatentable over claims 1-49 of U.S. Patent No. 12,371,683 in view of Teschner et al (WO2011/034604, reference of the IDS filed 2/12/2025), Han et al (U.S. 2019/0030076), Sandborn et al (Alimentary Pharmacology & Therapeutics, 2018, Vol. 48, pp. 65-77), Adler et al (U.S. 2011/0044977, reference of the IDS filed 5/16/2022), Boekhout et al (The Oncologist, 2011, Vol. 16, pp. 800-810) and Cingo (mAbs, 2009, Vol.1, pp. 216-212) is maintained for reasons of record.
Claim 1-3 of the ‘683 patent meets the limitations of the PH20 variant of instant claims 1, 24, 27, 30 and 46.
Claims 4-7 of the ‘683 patent encompass the PH20 variants of SEQ ID NO: 79, 87 and 99. SEQ ID NO: 99 meets the limitation of instant claims 32, 33, 40, 41, 44 and 45 for a PH20 variant which consists of, or comprises SEQ ID NO: 44.
RESULT 1
US-17-052-952-44
Query Match 100.0%; Score 2327; DB 1; Length 431;
Best Local Similarity 100.0%;
Matches 431; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 60
Qy 61 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 120
Qy 121 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 180
Qy 181 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 240
Qy 241 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 300
Qy 301 IWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 IWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 360
Qy 361 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 420
Qy 421 CIADGVCIDAF 431
|||||||||||
Db 421 CIADGVCIDAF 431
SEQ ID NO: 79 and 87 meet the limitations of a PH20 variant which comprises SEQ ID NO: 44 in instant claims 32, 33, 40, 41, 44, and 45.
RESULT 1
US-17-052-952-44
Query Match 94.9%; Score 2327; DB 1; Length 431;
Best Local Similarity 100.0%;
Matches 431; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 3 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 62
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 60
Qy 63 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 122
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 120
Qy 123 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 182
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 180
Qy 183 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 242
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 240
Qy 243 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 302
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 300
Qy 303 IWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 362
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 IWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 360
Qy 363 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 422
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 420
Qy 423 CIADGVCIDAF 433
|||||||||||
Db 421 CIADGVCIDAF 431
RESULT 1
US-17-052-952-44
Query Match 99.6%; Score 2327; DB 1; Length 431;
Best Local Similarity 100.0%;
Matches 431; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 60
Qy 61 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 120
Qy 121 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 180
Qy 181 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 240
Qy 241 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 300
Qy 301 IWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 IWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 360
Qy 361 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 420
Qy 421 CIADGVCIDAF 431
|||||||||||
Db 421 CIADGVCIDAF 431
SEQ ID NO: 99 of claims 19, 20 of the ‘683 patent meets the limitations of instant claims 1, 24, 46, for the 15 amino acid substitutions of part (i), truncation before F38 which meets the limitation of an N-terminus deletion of residues M1-N37 of part (ii) and truncation after F468 at the C terminus which meets the limitation of the C-terminus ending with an amino acid residue F468 also in instant claim 30; an N-terminal deletion of M1-N37 in claims 1, section (ii) and 27 and a C-terminal deletion wherein the variant ends with an amino acid residue of I465 to S490 in claim 1 section (iii), and 30; the deletion of amino acid residues M1-N37 of SEQ ID NO: 1 in claims 1 and 46 section (ii), and claims 27, 42 and 43; wherein the variant ends with the amino acid F468 in instant claims 30, 42, 43:
RESULT 1
US-17-052-952-1
Query Match 96.3%; Score 2242; DB 1; Length 509;
Best Local Similarity 96.5%;
Matches 416; Conservative 5; Mismatches 10; Indels 0; Gaps 0;
Qy 1 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 38 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 97
Qy 61 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 98 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 157
Qy 121 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 158 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 217
Qy 181 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 218 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 277
Qy 241 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 278 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 337
Qy 301 IWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 360
|||: |: :|| : ||:| ||||||||||||||||||||||||||||||||||||
Db 338 IWGTLSIMRSMKSCLLLDNYMETILNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 397
Qy 361 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 398 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 457
Qy 421 CIADGVCIDAF 431
|||||||||||
Db 458 CIADGVCIDAF 468
SEQ ID NO: 87 meets the limitations of instant claim 134 for the 15 amino acid substitutions of part (i), truncation before F38 which meets the limitation of an N-terminus deletion of residues M1-N37 of part (ii) and truncation after K470 at the C terminus which meets the limitation of the C-terminus ending with an amino acid residue K470 in claim 134.
RESULT 1
US-17-052-952-1
Query Match 96.4%; Score 2251; DB 1; Length 509;
Best Local Similarity 96.5%;
Matches 418; Conservative 5; Mismatches 10; Indels 0; Gaps 0;
Qy 1 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 38 FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLG 97
Qy 61 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 98 YYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARN 157
Qy 121 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 158 WKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWG 217
Qy 181 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 218 YYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLY 277
Qy 241 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 278 VRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIV 337
Qy 301 IWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 360
|||: |: :|| : ||:| ||||||||||||||||||||||||||||||||||||
Db 338 IWGTLSIMRSMKSCLLLDNYMETILNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDY 397
Qy 361 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 398 LHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDV 457
Section 804IIb of the M.P.E.P. states
The specification can be used as a dictionary to learn the meaning of a term in the patent
claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d
1065, 1067 (Fed. Cir. 1999).
In the instant case, the specification defines the instant PH20 variants as having the characteristics of increased thermal stability compared to mature wild-type PH20 and enzymatic activity which exceeds or is similar to that of mature wild-type PH20 (page 20, lines 17-23).
The claims of the patent do not teach a composition or formulation for subcutaneous injection comprising the PH20 variants of SEQ ID NO: 79, 87 or 99 admixed with Ustekinumab, or a composition comprising the PH20 variant of claim 1 of the ‘683 patent admixed with Ustekinumab, or the subcutaneous administration of the combination of variant PH20 and Ustekinumab to treat autoimmune disease in a patient in need thereof.
Teschner et al teach the co-formulation of hyaluronidase and immunoglobulin for the treatment of an autoimmune disease (page 5, lines 6-9). Teschner et al teach that the hyaluronidase can be PH20, or a truncated form thereof (page 3, lines 20-21). Teschner et al teach that the co-formulation compositions are formulated for subcutaneous administration (page 2, lines 21-23),
Han et al teach that Crohn’s disease is an autoimmune disease (claim 28 of ‘076).
Sandborn et al teach the administration of subcutaneous Ustekinumab to patients with Crohn’s disease every 8 weeks or every12 weeks (abstract). Sanborn et al teach that the subcutaneous Ustekinumab maintained clinical response and remission through week 92.
It would have been prima facie obvious at the time prior to the effective filing date to formulate the Ustekinumab with the PH20 variant of the claims of the ‘258 patent, and to administer said formulation subcutaneously in a method of treating Crohn’s Disease. One of skill in the art would have been motivated to do so because instant claim 37 requires that the PH20 variant co-formulated with Ustekinumab is administered subcutaneously, and because Teschner et al teach that the co-formulations are formulated for subcutaneous administration.
Adler et al teach formulations of anti-Her antibody including hyaluronidase for subcutaneous injection (abstract). Adler et al teach “formulation X” comprising 120mg trastuzumab, 20mM histidine buffer, pH 5.5, 210 mM trehalose, 10mM methionine and 0.04% polysorbate 20 with 2000 U/ml PH20 (page 23, heading for Table 1) which fulfills the requirements of claims 2 and 5 wherein the pharmaceutically acceptable additives are a buffer, stabilizer and a surfactant, claim 8, requiring a sugar, and a non-ionic surfactant and claims 3, requiring a histidine buffer, claims 48, and 49 requiring a histidine buffer and a pH 4-8.3, a surfactant which is polysorbate 20, trehalose as a stabilizer which is a sugar and methionine which is a stabilizer, claim 9 requiring polyoxyethylene monolauryl ether which is a synonym for polysorbate 20, and claim 4 wherein the buffer is at pH 4-8. The formulation X of Adler et al fulfills the requirement for claim 6 for trehalose; claim 7 for the sugar, trehalose, being at a concentration of 210mM; claim 10 for the surfactant, polysorbate 20, at a concentration of 0.04%; claim 11 for the immunoglobulin at a concentration of 120 mg/ml; claim 12 for the PH20 at 2000 U/ml; and claims 13 and 14 for the immunoglobulin at a concentration of 120 mg/ml; the PH20 at 2000U/ml; histidine buffer at 20mM, trehalose at 210mM, polysorbate at 0.04%, methionine at 10mM and a pH of 5.5.
Cingoz teaches that Ustekinumab is a human IgG1 monoclonal antibody (abstract). Boekhout et al teach that Trastuzumab is a humanized IgG1 monoclonal antibody (abstract)
It would have been prima facie obvious to combine Ustekinumab with the PH20 variants of the ‘683 patent having increased thermal stability and similar or higher hyaluronidase activity to that of wild type PH20 in a composition formulated for subcutaneous injection as in the composition of Adler et al. One of skill in the art would have been motivated to do so based on the teachings of Teschner et al regarding the co-formulation of hyaluronidase and immunoglobulin for the treatment of an autoimmune disease, the teachings of Han et al that Crohn’s Disease is an autoimmune disease, and the teachings of the abstract of Sanborn et al that subcutaneous Ustekinumab maintained clinical response and remission for 92 weeks. One of skill in the art would have looked to the co-formulation of Adler et al because Trastuzumab is a humanized IgG1 antibody and Ustekinumab is a human IgG1 monoclonal antibody. Thus, a large portion of the structure of the two antibodies are similar providing a reasonable expectation of success in the substitution of Ustekinumab for Trastuzumab.
Applicant argues that none of the cited claims of the ‘683 patent alone or in combination with Teschner, Han, Sandborn Adler, Bockhout or Cingoz teach or suggest a composition comprising Ustekinumab and a claimed PH20 variant. Applicant further argues that Sanborn related to the effects of Ustekinumab on patients with Crohn’s disease and makes no mention of the use of hyaluronidase or the PH20 variant. Applicant points out that Han teaches the addition of 15-PGDH to PGE-2 expressing cells and that there ae no teachings regarding hyaluronidase or Ustekinumab. Applicant argues that Teschner relates to co-formulation of hyaluronidase with antibodies , but fails to teach a composition comprising the PH20 variant of the claims and Ustekinumab. Applicant argues that Adler teaches a formulation of an anti-Her2 antibody with hyaluronidase that is not PH20. Applicant further points out that there are known antibody formulations that do not utilize a hyaluronidase, and that Ustekinumab is approved for subcutaneous injection but is not formulated with a hyaluronidase. Applicant states that Boekhout relates to trastuzumab and that Cingoz related to clinical trials involving subcutaneous injection of Ustekinumab. Applicant concludes there is no teaching or suggestion to produce a composition comprising Ustekinumab and a PH20 variant of the invention.
This has been considered but not found persuasive. In response to applicant's argument that none of Teschner, Han, Sandborn Adler, Bockhout or Cingoz teach or suggest the composition comprising Ustekinumab and the claimed PH20 variant., the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Claims 1-14, 24, 27, 30, 32-34, 36, 37 and 40-49 are rejected. Claim 50 is objected to for an informality.
Conclusion
THIS ACTION IS MADE FINAL. 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 KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643