Patent Application 16066638 Rejection Details

Title: BINDING MEMBERS WITH ALTERED DIVERSITY SCAFFOLD DOMAINS
Application Information

Invention Title: BINDING MEMBERS WITH ALTERED DIVERSITY SCAFFOLD DOMAINS
Application Number: 16066638
Submission Date: 2025-04-10T00:00:00.000Z
Effective Filing Date: 2018-06-27T00:00:00.000Z
Filing Date: 2018-06-27T00:00:00.000Z
National Class: 506
National Sub-Class: 018000
Examiner Employee Number: 81538
Art Unit: 1684
Tech Center: 1600
Rejection Summary

102 Rejections: 1
103 Rejections: 1
Cited Patents

The following patents were cited in the rejection:
US 1621070🔗
US 1600341🔗
Office Action Text



    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 .

DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/30/2025 has been entered.
Claims Pending	54,63,64,86,88,92,94,100-103,107,112,115,128-136,138-147,149-153
Claims Withdrawn	100-102,112,115,146,147 
Claims Under Consideration	54,63,64,86,88,92,94,103,107,128-136,138-145,149-153


Priority
	The present application was filed 06/27/2018 and is a 371 of 
PCT/EP2017/050337 filed 01/09/2017.
	Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to UNITED KINGDOM document no. 1600341.0 filed 01/08/2016 and 
no. 1621070.0 12/12/2016.  Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.

Claim Interpretation
	Claim 107’s recitation of “artificial N and C terminals generated by cyclisation and linearization of the donor diversity scaffold domain” is interpreted as a product by process limitation wherein the “artificial N and C terminals” are not limited to the process steps recited in the claim in accordance with MPEP 2113. Thus the claim is interpreted as reciting --wherein artificial N and C terminals 

Maintained Claim Rejection(s) - 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)(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.

Claim(s) 54,63,64,103,107,128,131-136,138-142,145 plus 151 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bazirgan et al (US PG-Pub 20160159928).
Bazirgan et al teach throughout the document and especially the abstract, figures 16-17,21, document claims 178,184 187, paragraphs 0016-0058,0705 and/or examples 1-2,5 at least antibody libraries bearing ultralong CDR3Hs for grafting in various cytokines or cysteine (cystine) rich peptide toxins into various human immunoglobulins thereof. One Bazirgan library SEQ IDs 925-955 constitutes a population of fusion proteins and comprises SEQ ID 941, for example, including donor diversity scaffold domain with donor interaction sequences like: ShK (Stichodactyla toxin), having primary sequence RSCIDTIPKSRCTAFQCKHSMKYRLSFCRKTCGTC bearing disulfides between cysteines 3-35, 12-29 and 17-32, which binds the extracellular epitope of Kv1.3, an ion channel integral membrane protein target, blocking potassium influx; or IL8 (each per said figure 21) either inserted into a recipient diversity scaffold domain, that is: the donor diversity scaffold domains have a donor scaffolds and donor interaction sequences and recipient diversity scaffold domains have a recipient scaffold and recipient interaction sequence(s); the fusion proteins are covalently and non-covalently associated with light chain multidomain binding partners, forming heterodimers and such that: the recipient diversity scaffold domain is an antibody variable domain and the donor diversity scaffold domain replaces a human CDR3H region in VH4-34 or variants thereof; and the amino and carboxy termini of donor diversity scaffold domains are fused to the recipient diversity scaffold domain without linkers. Said Bazirgan passages teach the donor interaction sequences or the recipient interaction sequences as diverse in populations. The foregoing reads on claims 54, 63, 64, 103, 107, 128(i),131,135, 136,138 & 151 when the fusion protein and the partner domain such as a light chain necessarily bind to the same target molecule, 139,140,141,142 and 145. Moreover, and as in claims 132,133,134 as well as further reading on of claim 135, in paragraph 0465 Bazirgan et al teach phage display thereof such antibodies in scFv format.
***
Please note that the above rejection has been clarified and updated from the original version to better address Applicants’ new and/or amended claims.

Response to Arguments
The remarks accompanying the present response argue not all elements are taught.
Applicant’s arguments have been fully considered but they are not deemed persuasive for the following reasons.
More particularly starting at p 11, the remarks allege the examiner is being arbitrary and capricious, improperly relying upon two inconsistent interpretations of the Bazirgan reference to account for the donor diversity scaffold domain set forth in in claims 54 and 64, noting replacement of a native CDRH3 of a human antibody for a ultralong bovine CDRH3 (e.g. BLVH12) including a ShK insert as in Bazirgan SEQ ID 949 does not anticipate the claims since it has greater than 4 residue linkers.
In response, first it is noted that the current amendments to claims 54 and 63 do not narrow the scope of the claimed subject matter in any way. Second, rather than the previous action being improper, it is the remarks that conflate the presently claimed donor diversity domain for the presently claimed donor interaction sequence, indeed Bazirgan SEQ ID 949 is immaterial to the individual antibodies in Bazirgan's SEQ ID 925-955 library that DO meet all the limitations of claims 54 and 64, such as Bazirgan SEQ ID 941 -- as well as SEQ IDs 925 and 926 – three fusion proteins that are clearly encompassed by the rejected claims. 
From Bazirgan figure 21 sheets 62-71 and employing Applicant's own assignments reflected pp 12-13 of the current remarks, SEQ ID 941 includes a donor scaffold domain with NO linkers that replaces a human CDR3H in a VH4-34 heavy chain having recipient scaffold domains with BLVH12 bearing a ShK knob as a donor interaction sequence (underlined):
…Y
CTSVHOETKKYQS
RSCIDTIPKSRCTAFQCKHSMKYRLSFCRKTCGTC
SYTYNYEVVHVDVW
G…

Bazirgan SEQ ID 926 includes a donor scaffold domain with NO linkers that similarly replaces a human CDR3H in a VH4-34 heavy chain having recipient scaffold domains with BLVH12 bearing an IL8 knob as a donor interaction sequence (underlined):
…Y
CTSVHQETKKYQS
PRSAKELRCQCIKTYSKPFHPKFIKELRVIESGPHCANTEIIVKLSDGRELCLDPKENWVQRVVEKFLKRAENSGSG
SYTYNYEWHVDVW
G…

Finally, Bazirgan SEQ ID 925 includes a donor scaffold domain once again with NO linkers that replaces a human CDR3H in a VH4-34 heavy chain having recipient scaffold domains simply with BLVH12 bearing its native knob as a donor interaction sequence between the same stalk sequences (underlined) as SEQ ID 926 and 941.
…Y
CTSVHQETKKYQS
CPDGYRERSDCSNRPACGTSDCCRVSVFGNCLTTLPVSY-
SYTYNYEWHVDVW
G…

	Accordingly, as opposed to the office acting arbitrarily and capriciously, it is the current remarks that ignores three species of Bazirgan at least that unequivocally anticipate the genus set forth in claims 54 and 63. 

Maintained Claim Rejection(s) - 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.

Claims 54,63,64,103,107,128,131-136,138-142,145 plus 151 and 86,88,92,94,129,130,143,144 plus 149-150,152-153 are rejected under 35 U.S.C. 103 as being unpatentable over Bazirgan et al (US PG-Pub 20160159928) in view of Escher (WO 2014124677).
Bazirgan et al is relied on as above and CDR3H; and diverse donor interaction sequences of claims 144,150 line 3.
Bazirgan et al do not explicitly teach: a donor diversity scaffold replacing a VL (light chain variable domain) CDR1 or CDR2 recipient diversity scaffold domain; nor explicitly such VL associated with a VH (heavy chain variable domain) partner domain connected by a flexible linker per claims 86 & 88,92,94,152-153; nor diverse linkers of claims 129,130,149,150 line 1.
Like claims 86,88,94,152-153 Escher suggests throughout the document and especially the abstract and document claim 12, an antibody acceptor (recipient) framework for grafting non-human donor sequences such as rabbit light chain CDR1s and/or CDR2s donors into light chain framework Escher SEQ ID 2 that is associated therewith heavy chain variable domain Escher SEQ ID 1. And at p 23 lines 15-26 and/or p 10 line 23 and/or p 6 lines 28-35 to p 7 lines 1-3, Escher teaches such antibody may be in scFv format with diverse linkers like claims 92,129,130,149 and 150 line 1.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have grafted cystine rich sequences as suggested by Bazirgan et al into Escher's antibody acceptor framework. 
One of ordinary skill in the art would have been motivated to have grafted cystine rich sequences as suggested by Bazirgan et al into Escher's antibody acceptor framework and had a reasonable expectation of success in doing so since Escher's acceptor framework is drawn to grafting rabbit CDRs, which likewise have extra cystines, whereas Escher's antibody acceptor framework beneficially yields a molecule with such CDRs displayed properly (see p 12 lines 8-18).
And regarding claims 143-144 as interpreted in MPEP 2144.06, the courts have held, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose is obvious.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Here, it is obvious to combine a CDR peptide sequence that binds to an external Kv1.3 epitope target with a toxin sequence that binds the same in an effort to form an antibody useful for the same purpose of blocking cellular potassium influx (see above).
***
Please note that the above rejection has been clarified and updated from the original version to better address Applicants’ currently amended claims.

Response to Arguments
Applicant does not offer further arguments regarding the above obviousness rejection(s) beyond what was set forth with regard to the 35 U.S.C. § 102 rejection, above.  To the extent that Applicant is merely repeating their previous argument, the examiner respectfully submits that those issues were adequately addressed in the above section(s), which is/are incorporated in their entireties herein by reference.

Maintained Claim Rejection(s) – 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 obviousness-type 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); and  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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. 
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).

Claims 54,63,64,103,107,128-136,138-142,145 and 86,88,94,143 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1(ii),2-6,14,20 of copending Application No. 16/629,877 (referred to hereafter as '877) in view of Bazirgan et al (US PG-Pub 20160159928)
	Although the conflicting claims are not identical, they are not patently distinct from each other because, for example, said present claims constitute structural variants, the very compound for treating autoimmune disease as recited in the conflicting claims for example of ‘877; or alternatively overlap in scope to a large extent and, as a result, the overlapping claims would be rendered obvious.
	The following is illustrative.
	For claim(s) 86,94, '877 claims VL recipients and CDR1L and CDR2L replacements (e.g. see claim(s) 3-4)
	For claim(s) 88, '877 claims VH partners (e.g. see claim(s) 3).
	For claim(s) 103, '877 claims linking donor native amino and carboxy termini to a recipient scaffold (e.g. see claim(s) 5)
	Additionally, it would have been obvious to one having ordinary skill in the art at the time the invention was made to modify embodiments of '877 that fall outside the scope of the present application to select a specifically disclosed embodiment that falls within the scope of the present application because each set of claims concern ShK peptide grafted antibody compositions with similar physiochemical properties and/or biological activities stemming from a common core structure. Furthermore, the skilled artisan would have been motivated to make such a modification because such changes are disclosed as “preferred” in so far as the dependent claims of ‘877 “teach toward” presently claimed materials, especially in view of Bazirgan et al, who as detailed supra suggest the same materials.
This is a provisional obviousness-type double patenting rejection.

Response to Arguments
	Applicants request that the rejection be held in abeyance until an indication of allowable subject matter occurs.
In this vein, Applicant is advised any abeyance described in MPEP 804(I)(B) concerns applications for which formal matters remain but are otherwise allowable. Here, rejections under 35 USC 102 and 103 remain, thus until a TD is filed or Applicant persuasively argues the present claims are not obvious over application 16629877, the foregoing double patenting rejection shall be maintained.


All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114.  See MPEP § 706.07(b). 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.



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/CHRISTOPHER M GROSS/Primary Examiner, Art Unit 1684