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 .
1. Election of Species
This application contains claims directed to the following patentably distinct species –
Claims 26-29 – Applicants are to elect one heavy chain SEQ ID NO and one light chain SEQ ID NO
The species are independent or distinct because each sequence would require its own potentially non-overlapping search. In addition, these species are not obvious variants of each other based on the current record. Therefore, there is a search and/or examination burden for the patentably distinct species as set forth above.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no
generic claim is finally held to be allowable. Currently, claims 19-25 and 29-46 are generic.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected species or grouping of patentably indistinct species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species or grouping of patentably indistinct species.
Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
2. Election by Telephone
A voicemail was left with Craig Crandall on 11/30/25, which was returned on 12/1/25. SEQ ID NO:11 and 31 (identified as construct A120) were elected. However, upon further review of the prior art, all sequences have been examined.
3. Formal Matters
Claims 19-36 are pending and are the subject of this Office Action.
4. Claim Objections
A. Claim 20 is objected to since it recites “comprises an amino acid sequence”. It is suggested that the claim mimic the language of claim 22, which recites “comprising the amino acid sequence”.
B. Claim 24 is objected to since there is a space between “anti-” and “TGF-B”.
C. Claim 24 is objected to since “single domain” should be hyphenated in both instances.
D. Claims 26 and 29 are objected to since they recite “any one of”; however, they each only refer to a single claim.
E. Claim 32 is objected to since “myelo fibrosis” should be written as “myelofibrosis”.
5. Claim Rejections - 35 USC § 112(a) – scope of enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 31 and 32 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for treatment of all the conditions recited in claim 32, does not reasonably provide enablement for prevention of any disease condition. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
In In re Wands, 8USPQ2d, 1400 (CAFC 1988) page 1404, the factors to be considered in determining whether a disclosure would require undue experimentation include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
With regard to prevention, the Examiner is unable to find a definition in the specification and is, therefore, interpreting this term to mean that a disease or condition will not occur in 100% of the patients treated with the claimed bifunctional molecule. Applicants have not provided any guidance or working examples that the molecule of the invention can inhibit the occurrence of the claimed conditions, nor is it predictable that a molecule of the invention could have such an effect.
These factors lead the Examiner to hold that undue experimentation is necessary to practice the invention as claimed.
6. Claim Rejections - 35 USC § 112(a) – written description
Claims 19, 20, 22 and 30-36 are rejected under 35 U.S.C. 112, first paragraph, as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
These are genus claims. Other than a “bifunctional antagonist molecule”, the specification and claims do not indicate what distinguishing attributes are shared by the members of the genus. Thus, the scope of the claims includes numerous structural variants, and the genus is highly variant because a significant number of structural differences between/among genus members is permitted. The specification and claims do not provide any guidance as to what changes should be made. Structural features that could distinguish compounds in the genus from others classes, including nucleic acid, protein and small molecule are missing from the disclosure. No common structural attributes identify the members of the genus. Furthermore, a search of the prior art does not identify any known bifunctional TNF-TGB inhibitors other than MA-35 (see Shima et al. in the rejection below under 35 USC 103).
Though the focus is not on bifunctional TNF-TGB-binding molecules, Konde (page 9, right column, 3rd paragraph) does discuss the challenges with producing bifunctional molecules, especially regarding in vivo use –
Challenges, however, must be carefully navigated when implementing synergistic targeted protein degradation strategies. One major concern is the risk of additive or synergistic toxicity, which may arise from combining multiple active agents or employing complex bifunctional molecules with overlapping or interacting biological effects. Additionally, there can be pharmacokinetic mismatches between agents that differ in bioavailability, half-life, or tissue distribution, complicating dose optimization and timing. From a development standpoint, such combination strategies introduce greater complexity in drug discovery, requiring sophisticated design, synthesis, and optimization processes, as well as more extensive regulatory evaluation. Furthermore, there is the potential for unpredictable biological cross-effects or off-target interactions, especially in cases where the mechanisms of the combined agents intersect within overlapping cellular pathways or interact with unintended proteins.
Therefore, the general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, MA-35 and antibodies, alone, are insufficient to describe the genus. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus. Thus, Applicant was not in possession of the claimed genus at the time the invention was made.
7. Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Regarding claim 24, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
8. Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
A. Claims 19, 21, 23-25 and 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Shima et al. in view of Nolan.
The claims are generally drawn to a bifunctional antagonist molecule that specifically binds TNF and TGF-b.
Shima teaches MA-35, which antagonizes both TNF-a and TGF-b and attenuates renal fibrosis The compound acts via inhibiting IkB kinase phosphorylation in the TNF pathway and Smad3 in the TGF-b pathway (Abstract) instead of directly binding TNF-a and TGF-b as required in claim 1. Regardless, Shima does provide motivation to target both TNF-a and TGF-b for the treatment of fibrosis. Regarding claim 30, given the teachings of Shima in the paragraph bridging pages 3-4 of Shima as well as page 9 under “Animals”, the artisan would immediately envision pharmaceutical compositions for these in vivo experiments. Claims 31 and 32 are met by Shima’s teaching of treatment of renal fibrosis.
Though Shima does not directly target TNF-a and TGF-b, Nolan does teach the use of bifunctional antibodies and their potential clinical applications. Given this, it would have been obvious to have produced bifunctional antibodies to both TNF-a and TGF-b, themselves, given their therapeutic potential as taught by Shima which inhibits targets downstream molecules in these pathways. Regarding claims 23 and 25, see Figure 2B of Nolan. Regarding claim 25, see Figure 1B and C.
B. Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Shima et al. in view of Nolan and further in view of Wong et al. and further in view of Tolcher et al. The teachings of Shima and Nolan are seen in paragraph A of this section. Neither teaches the claimed TNF or TGF antigen-binding molecules. However, Wong teaches infliximab, which binds the TNF-a ECD and Tolcher teaches LY3022859, which binds the TGF-b ECD.
Therefore, given the teachings of Shima and Nolan, it would have been obvious at the time of the instant invention to have made a bifunctional antibody comprising infliximab and LY3022859 in order to block both TNF-a and TGF-b and, thereby, treat fibrosis.
C. Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Shima et al. in view of Nolan and further in view of Chou et al. (U.S. Patent No. 8,669,350) and further in view of Bedi et al. (U.S. Patent No. 8,993,524). The teachings of Shima and Nolan are seen in paragraph A of this section. Neither teaches the claimed TNF or TGF ligands. However, Chou teaches the TNF-a ligands of SEQ ID NO:1, 2 or 5 and Bedi teaches the TGF-b ligands of SEQ ID NO:7 and 9.
Regarding claim 22, as stated above in paragraph A under 35 USC § 112(a), it appears that SEQ ID NO:1-5 and 6-9 are correct (i.e. these represent the ligands as opposed to the recited binding polypeptide). Therefore, the claim is rejected here.
SEQ ID NO:1
Patent No. 8669350
GENERAL INFORMATION
APPLICANT: CHOU, Min-Yuan
APPLICANT: CHIU, Wei-Chun
APPLICANT: LAI, Ya-Ping
TITLE OF INVENTION: TRIMERIC OR HEXAMERIC Fc FUSION PROTEINS
FILE REFERENCE: 2668-0126PUS1
CURRENT APPLICATION NUMBER: US/13/588,752
CURRENT FILING DATE: 2012-08-17
NUMBER OF SEQ ID NOS: 86
SEQ ID NO 66
LENGTH: 190
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
Query Match 100.0%; Score 1093; Length 190;
Best Local Similarity 100.0%;
Matches 190; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 IYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTKCHKGTYLYNDCPGPGQDTDC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 IYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTKCHKGTYLYNDCPGPGQDTDC 60
Qy 61 RECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDRDTVCGCRKNQYRHYWSENLF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDRDTVCGCRKNQYRHYWSENLF 120
Qy 121 QCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECVSCSNCKKSLECTKLCLPQIEN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECVSCSNCKKSLECTKLCLPQIEN 180
Qy 181 VKGTEDSGTT 190
||||||||||
Db 181 VKGTEDSGTT 190
SEQ ID NO:2
Patent No. 8669350
SEQ ID NO 16
LENGTH: 247
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic TNF_RII EC Domain
Query Match 100.0%; Score 1318; Length 247;
Best Local Similarity 100.0%;
Matches 235; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPGQHAKVFCTKTSDTVCDSCEDST 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10 LPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPGQHAKVFCTKTSDTVCDSCEDST 69
Qy 61 YTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTCRPGWYCALSKQEGCRLCAPLRK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 70 YTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTCRPGWYCALSKQEGCRLCAPLRK 129
Qy 121 CRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICRPHQICNVVAIPGNASMDAVCTS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 130 CRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICRPHQICNVVAIPGNASMDAVCTS 189
Qy 181 TSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTSFLLPMGPSPPAEGSTGD 235
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 190 TSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTSFLLPMGPSPPAEGSTGD 244
SEQ ID NO:5
Patent No. 8669350
SEQ ID NO 66
LENGTH: 190
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
Query Match 100.0%; Score 842; Length 190;
Best Local Similarity 100.0%;
Matches 145; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 IYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTKCHKGTYLYNDCPGPGQDTDC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 IYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTKCHKGTYLYNDCPGPGQDTDC 60
Qy 61 RECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDRDTVCGCRKNQYRHYWSENLF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDRDTVCGCRKNQYRHYWSENLF 120
Qy 121 QCFNCSLCLNGTVHLSCQEKQNTVC 145
|||||||||||||||||||||||||
Db 121 QCFNCSLCLNGTVHLSCQEKQNTVC 145
SEQ ID NO:7
Patent No. 8993524
GENERAL INFORMATION
APPLICANT: THE JOHNS HOPKINS UNIVERSITY
APPLICANT: BEDI, Atul
APPLICANT: RAVI, Rajani
TITLE OF INVENTION: COMPOSITIONS AND METHODS FOR TARGETED IMMUNOMODULATORY ANTIBODIES
TITLE OF INVENTION: AND FUSION PROTEINS
FILE REFERENCE: JHU3260-4
CURRENT APPLICATION NUMBER: US/13/582,717
CURRENT FILING DATE: 2012-09-04
PRIOR APPLICATION NUMBER: PCT/US2011/027317
PRIOR FILING DATE: 2011-03-04
PRIOR APPLICATION NUMBER: US 61/435,671
PRIOR FILING DATE: 2011-01-24
PRIOR APPLICATION NUMBER: US 61/311,255
PRIOR FILING DATE: 2010-03-05
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 87
LENGTH: 137
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 764; Length 137;
Best Local Similarity 100.0%;
Matches 137; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQE 60
Qy 61 VCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDE 120
Qy 121 CNDNIIFSEEYNTSNPD 137
|||||||||||||||||
Db 121 CNDNIIFSEEYNTSNPD 137
SEQ ID NO:9
SEQ ID NO 88
LENGTH: 162
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 903; Length 162;
Best Local Similarity 100.0%;
Matches 162; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TIPPHVQKSDVEMEAQKDEIICPSCNRTAHPLRHINNDMIVTDNNGAVKFPQLCKFCDVR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 TIPPHVQKSDVEMEAQKDEIICPSCNRTAHPLRHINNDMIVTDNNGAVKFPQLCKFCDVR 60
Qy 61 FSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAA 120
Qy 121 SPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD 162
||||||||||||||||||||||||||||||||||||||||||
Db 121 SPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD 162
D. Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Shima et al. in view of Nolan and further in view of Hellendoorn et al. (U.S. Patent No. 7,754,853). The teachings of Shima and Nolan are seen in paragraph A of this section. Neither teaches SEQ ID NO:14 and 15. However, Hellendoorn does teach this TNF-a-binding polypeptide.
SEQ ID NO:14
Patent No. 7754853
GENERAL INFORMATION
APPLICANT: HELLENDOORN, Koen
APPLICANT: BAKER, Matthew
APPLICANT: CARR, Francis J.
TITLE OF INVENTION: TNF ALPHA-BINDING POLYPEPTIDE COMPOSITIONS AND METHODS
FILE REFERENCE: MER-131
CURRENT APPLICATION NUMBER: US/11/005,726
CURRENT FILING DATE: 2004-12-07
PRIOR APPLICATION NUMBER: 10/495,146
PRIOR FILING DATE: 2004-05-10
PRIOR APPLICATION NUMBER: PCT/EP02/12566
PRIOR FILING DATE: 2002-11-11
PRIOR APPLICATION NUMBER: EP 01126858.8
PRIOR FILING DATE: 2001-11-12
NUMBER OF SEQ ID NOS: 165
SEQ ID NO 161
LENGTH: 450
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: anti-TNF alpha chimeric antibody heavy chain
Query Match 100.0%; Score 2407; Length 450;
Best Local Similarity 100.0%;
Matches 450; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVKLEESGGGLVQPGGSMKLSCVASGFIFSNHWMNWVRQSPEKGLEWVAEIRSKSINSAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVKLEESGGGLVQPGGSMKLSCVASGFIFSNHWMNWVRQSPEKGLEWVAEIRSKSINSAT 60
Qy 61 HYAESVKGRFTISRDDSKSAVYLQMTDLRTEDTGVYYCSRNYYGSTYDYWGQGTTLTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 HYAESVKGRFTISRDDSKSAVYLQMTDLRTEDTGVYYCSRNYYGSTYDYWGQGTTLTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE 360
Qy 361 LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
SEQ ID NO:15
SEQ ID NO 163
LENGTH: 214
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: anti-TNF alpha chimeric antibody light chain
Query Match 100.0%; Score 1110; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DILLTQSPAILSVSPGERVSFSCRASQFVGSSIHWYQQRTNGSPRLLIKYASESMSGIPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DILLTQSPAILSVSPGERVSFSCRASQFVGSSIHWYQQRTNGSPRLLIKYASESMSGIPS 60
Qy 61 RFSGSGSGTDFTLSINTVESEDIADYYCQQSHSWPFTFGSGTNLEVKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLSINTVESEDIADYYCQQSHSWPFTFGSGTNLEVKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
E. Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Shima et al. in view of Nolan and further in view of Lee et al. (U.S. Patent No. 9,598,486). The teachings of Shima and Nolan are seen in paragraph A of this section. Neither teaches SEQ ID NO:26 and 27. However, Lee does teach this TGF-b-binding polypeptide.
SEQ ID NO:26
Patent No. 9598486
GENERAL INFORMATION
APPLICANT: GENZYME CORP.
APPLICANT: BAYLOR COLLEGE OF MEDICINE
TITLE OF INVENTION: METHODS FOR TREATING OSTEOGENESIS IMPERFECTA
FILE REFERENCE: 554897 SA9-108WO
CURRENT APPLICATION NUMBER: US/14/772,708
CURRENT FILING DATE: 2015-09-03
PRIOR APPLICATION NUMBER: 61/883,151
PRIOR FILING DATE: 2013-10-26
PRIOR APPLICATION NUMBER: 61/875,399
PRIOR FILING DATE: 2013-09-09
PRIOR APPLICATION NUMBER: 61/803,647
PRIOR FILING DATE: 2013-03-20
NUMBER OF SEQ ID NOS: 21
SEQ ID NO 14
LENGTH: 447
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
Query Match 100.0%; Score 2355; Length 447;
Best Local Similarity 100.0%;
Matches 447; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSNVISWVRQAPGQGLEWMGGVIPIVDIANY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSNVISWVRQAPGQGLEWMGGVIPIVDIANY 60
Qy 61 AQRFKGRVTITADESTSTTYMELSSLRSEDTAVYYCASTLGLVLDAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQRFKGRVTITADESTSTTYMELSSLRSEDTAVYYCASTLGLVLDAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSV 240
Qy 241 FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY 300
Qy 301 RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK 360
Qy 361 NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG 420
Qy 421 NVFSCSVMHEALHNHYTQKSLSLSLGK 447
|||||||||||||||||||||||||||
Db 421 NVFSCSVMHEALHNHYTQKSLSLSLGK 447
SEQ ID NO:27
SEQ ID NO 15
LENGTH: 215
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
Query Match 100.0%; Score 1113; Length 215;
Best Local Similarity 100.0%;
Matches 215; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ETVLTQSPGTLSLSPGERATLSCRASQSLGSSYLAWYQQKPGQAPRLLIYGASSRAPGIP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ETVLTQSPGTLSLSPGERATLSCRASQSLGSSYLAWYQQKPGQAPRLLIYGASSRAPGIP 60
Qy 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYADSPITFGQGTRLEIKRTVAAPSVFIFP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYADSPITFGQGTRLEIKRTVAAPSVFIFP 120
Qy 121 PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL 180
Qy 181 TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 215
|||||||||||||||||||||||||||||||||||
Db 181 TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 215
F. Claims 33-36 are rejected under 35 U.S.C. 103 as being unpatentable over Shima et al. in view of Nolan and further in view of Tabasinezhad et al.
The claims are drawn to nucleic acids, vectors, host cells and methods of making a bifunctional antagonist molecule. The teachings of Shima and Nolan are seen above. Neither teach recombinant antibody production. However, Tabasinezhad does (e.g. section 2 under “Materials and Methods”). Given this, it would have been obvious to have produced any antibody, including that of Nolan, using this technique.
8. Prior Art of Interest Not Relied Upon
The following references are being cited for their background support –
A. Liu teaches the relationship between TNF-a and TGF-b during tumor formation.
B. Yoshimatsu teaches the relationship between TNF-a and TGF-b with regard to inducing EndMT of HDLECs.
C. Kriangkum teaches bifunctional single-chain recombinant antibodies.
D. Banner teaches the crystal structure of the TNF receptor – human TNFb complex, allowing for an understanding of receptor structure/function with regard to ligand-binding domains and ligand binding.
E. Naismith teaches the crystal structure of the human Type I TNF Receptor, allowing for an understanding of receptor structure/function.
F. Idress reviews the crystal structure of TNFa, TNFb, the extracellular domains of TNFR-1 (sTNFR-1), the TNFb/sTNFR1 complex and TNF mutants with altered affinity for TNFR-1 and TNFR-2, allowing for an understanding of receptor ligand binding domains.
G. Boesen teaches the crystal structure of the human TGF-b Receptor ligand-binding domain, allowing for an understanding of receptor structure/function with regard to ligand binding.
9. Conclusion
A. Claims 19-27 and 30-36 are not allowable.
B. Claims 28 and 29 are objected to since they depend from rejected claims. However, they are otherwise allowable.
Advisory information
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647