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 .
Applicant's arguments filed 3/13/2026 have been fully considered but they are not fully persuasive.
This action is being made non-final as new grounds of rejection not necessitated by amendment are set forth below.
Claims 1-2 and 21 have been cancelled. Claims 22-23 have been newly added.
Election/Restrictions
Applicant’s election without traverse of Group I and the antibody 31C8 having the CDRs listed in claim 1, part (3), in the reply filed on 9/23/2025 is acknowledged.
Claims 13-15, 17, and 19-20 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/23/2025.
Claim 3, part (3), recites the elected 31C8 antibody CDRs.
SEQ ID NOS: 39, 71, and 73 in claim 5, part (i), and SEQ ID NOS: 40 and 79 in claim 5, part (ii) contain the elected 31C8 antibody CDRs.
SEQ ID NOS: 39, 40, 71, 73, and 79 in claim 6, parts (3), (7), and (8), contain the elected 31C8 antibody CDRs.
SEQ ID NOS: 67, 75, and 77 in claim 7, part (i), and SEQ ID NOS: 69 and 81 in claim 7, part (ii) contain the elected 31C8 antibody CDRS.
SEQ ID NOS: 67, 69, 75, 77, and 81 in claim 8, parts (6), (7), and (8), contain the elected 31 C8 antibody CDRs.
SEQ ID NOS: 39 and 67 comprise SEQ ID NO: 17 where X1 is N, X2 is Q, and X3 is K. SEQ ID NOS: 71 and 75 comprise SEQ ID NO: 17 where X1 is A, X2 is E, and X3 is Q. SEQ ID NOS: 73 and 77 comprise SEQ ID NO: 17 where X1 is A, X2 is K, and X3 is K.
SEQ ID NO: 40 comprises SEQ ID NO: 30 where X4 is M.
SEQ ID NO: 79 comprises SEQ ID NO: 30 where X4 is L.
The other portions of the claims have not been searched with respect to prior art as they are directed to non-elected embodiments.
Priority
Applicant’s translation of the foreign priority document submitted 11/10/2022 was not accompanied by the required statement that the translation of the certified copy is accurate. Applicant cannot rely upon this document for benefit of its priority date with respect to any intervening art in the absence of the required statement. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
The priority claim is acknowledged.
Claim Rejections - 35 USC § 112
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 3-12, 16, 18, and 22-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The genus of antibodies encompassed by claims 3-12, 16, 18, and 22-23 are not adequately described. The antibody structures encompassed by the claims are highly variable.
Claim 3 is directed to CDRs “comprising a sequence set forth in SEQ ID” (emphasis added) throughout the claim. This language is considered to include subsequences of the recited sequences. This would include CDRs having a single amino acid in common with the recited sequences. This language is not considered to require the entirety of the recited sequences. This is in contrast to “comprising SEQ ID NO” or “comprising the sequence set forth in SEQ ID” (emphasis added). As such, the variability of CDR sequences for the recited antibodies is large.
Claims 5-6 are directed to heavy chain variable regions and light chain variable regions “comprising a sequence set forth in SEQ ID” (emphasis added) throughout the claims. This would include heavy chain variable regions and light chain variable regions having a single amino acid in common with the recited sequences. This language is not considered to require the entirety of the recited sequences. This is in contrast to “comprising SEQ ID” or “comprising the sequence set forth in SEQ ID” (emphasis added). As such, the sequence variability of heavy chain variable regions and light chain variable regions for the recited antibodies is large, particularly in view of the 80%identity limitations in claims 5-6.
Claims 7-8 are directed to heavy chains and light chains “comprising a sequence set forth in SEQ ID” (emphasis added) throughout the claims. This would include heavy chains and light chains having a single amino acid in common with the recited sequences. This language is not considered to require to the entirety of the recited sequences. This is in contrast to “comprising SEQ ID” or “comprising the sequence set forth in SEQ ID” (emphasis added). As such, the sequence variability of heavy chains and light chains for the recited antibodies is large.
The genus of antibodies encompassed by claims 1-12, 16, 18, and 22-23 is not adequately described. The antibody structures encompassed by the claims are highly variable. In the instant application, the specification and claims draw a fence around a perceived genus but the genus is not adequately described. The specification exemplifies specific antibodies in Tables 1-4 having the properties recited in the claims; however, the structural variability of the claimed antibodies is large. No reasonable structure-function correlation has been established that is commensurate in scope with the claims. The specification does not describe representative examples to support the full scope of the claims.
The claimed genus of antibodies is not adequately described.
Claims 3-12, 16, 18, and 22-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the anti-ST2 antibodies 7D1, 3C6, 31C8, 26A1, 8F4, and 17E2 having the specific sequences set forth in Tables 1-4 as discussed below, does not reasonably provide enablement for all antibodies encompassed by the claims. 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 and use the invention commensurate in scope with these claims.
The variability of antibody sequences encompassed by the claims is set forth above. The unpredictability of those antibody sequences having anti-ST2 binding activity in view of this sequence variability is set forth above.
In particular, the specification defines “ST2” as comprising variants, homologs, orthologs and paralogs of ST2. That is, the claimed antibodies can bind any species of ST2. However, the antibodies in the examples were raised against human ST2 and tested against only human ST2 and cynomolgus monkey ST2. The specification does not provide binding information for variants (and it is unclear what ST2 sequences these variants include or exclude) and other homologs, orthologs, and paralogs.
With respect to blocking binding of IL33/ST2 and signaling thereof (see claims 10 and 12), the specification only tests human IL33 and human ST2. The specification does not provide blocking binding information for ST2 variants (and it is unclear what ST2 sequences these variants include or exclude) and other homologs, orthologs, and paralogs of ST2 and other species of IL33.
With respect to ILR1, IL1R2, IL1R3, IL1R7, IL1R8 and IL1R9 binding (see claim 11), the specification only tests ILIR1/CD121a (Sino biological, 10126-H08H), IL1R2/CD121b (Sino biological, 10111-H08H), IL1R3/ILIRAP (Sino biological, 10121-H08H), IL1R7/IL-18RAcP (Sino biological, 10176-H08H), ILIR8/IL1RAPL1 (Sino biological, 10177-H08H), and IL1R9/IL1RAPL2 (Sino biological, 10156-H08H). See Example 14. The specification does not provide binding information for other species of IL1 receptors.
The specification does not provide antibody binding data corresponding to the characteristics required by claims 3 and 10-12 for a reasonable number of embodiments within the claims that are representative of the genus of antibodies being claimed.
It would constitute undue experimentation to determine which antibodies having sequences within the scope of the claims that bind ST2 (all forms encompassed by the claims) and have the activities recited in claims 10-12.
In In re Wands (8 USPQ2d 1400 (CAFC 1988)) the CAFC considered the issue of enablement in molecular biology. The CAFC summarized eight factors to be considered in a determination of "undue experimentation." These factors include: (a) the quantity of experimentation necessary; (b) the amount of direction or guidance presented; (c) the presence or absence of working examples; (d) the nature of the invention; (e) the state of the prior art; (f) the relative skill of those in the art; (g) the predictability of the art; and (h) the breadth of the claims.
In the instant application, the quantity of experimentation would be large, the working examples are not representative of the genus of antibodies being claimed, the breadth of the claims is large, and it would not have been predictable which antibodies having sequences within the scope of the claims would bind ST2 (all forms encompassed by the claims) and have the activities recited in claims 10-12.
The scope of the claims is not enabled.
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.
Claims 3, 5, 7, and 22 are rejected 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.
Claim 3 is confusing as to whether the last 6 lines of the claim are in reference to only part (3) which recite SEQ ID NOS: 17 and 30 or whether the limitations with respect to SEQ ID NO: 30 are also with respect to parts (2), (4), and (5). The “in addition” claim language is confusing and ambiguous.
Claim 3 is directed to six ST2 antibodies (numbered (1)-(6) in the claim where the heavy chain CDRs and light chain CDRs are recited.
Claim 5 now depends upon claim 3 and recites a list of heavy chain variable regions in part (i) and a list of light chain variable regions in part (ii). Part (iii) requires choosing one sequence from each of parts (i) and (ii). Claim 5 is confusing as it implies that (for example) SEQ ID NO:35 could be paired with SEQ ID NO: 79. However, this would be improperly dependent as none of antibodies (1)-(6) in claim 3 have the CDRs for the heavy chain variable region of SEQ ID NO: 35 paired with CDRs for the light chain variable region of SEQ ID NO: 79. The claim language in claim 5 is confusing. See by comparison claim 6. It appears that claim 5 should be cancelled and claim 6 should be made dependent upon claim 3. The CDRs recited in claim 3 must be retained in the heavy and light chain variable region sequences of claims 5-6 for proper dependency even in view of the at least 80% identity limitations.
Claim 7 now depends upon claim 3 and recites a list of heavy chains in part (i) and a list of light chains in part (ii). Part (iii) requires choosing one sequence from each of parts (i) and (ii). Claim 7 is confusing as it implies that (for example) SEQ ID NO: 77 could be paired with SEQ ID NO: 49. However, this would be improperly dependent as none of antibodies (1)-(6) in claim 3 have the CDRs for the heavy chain of SEQ ID NO: 77 paired with CDRs for the light chain of SEQ ID NO: 49. The claim language in claim 7 is confusing. See by comparison claim 8. It appears that claim 7 should be cancelled and claim 8 should be made dependent upon claim 3. The CDRs recited in claim 3 must be retained in the heavy and light chain sequences of claims 7-8 for proper dependency even in view of the at least 80% identity limitations.
Claim 22 is confusing in not clearly identifying that the limitations in this claim can only be in reference to claim 3, part (3). None of the other parts of claim 3 have the HCDR2 of SEQ ID NO: 17 or the LCDR2 of SEQ ID NO: 30.
Claim Rejections - 35 USC § 102
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 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.
Claims 3, 5-10, 12, 16, 18, and 22-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Smith et al. (U.S. Patent Application Publication 2014/0004107, of record).
As set forth above, the recitation of “comprising a sequence” in the instant claims includes variants having common subsequences such as single amino acids of the recited sequences.
Smith et al. discloses a fully human anti-ST2 antibody having a heavy chain/light chain of SEQ ID NO: 18/84 (Ab1). The LCDRs of SEQ ID NO: 84 are SEQ ID NOS: 106, 117, and 128. The HCDRs of SEQ ID NO: 18 are SEQ ID NOS: 40, 51, and 62. See at least abstract; paragraphs [0107, 0121, 0140, and 0154]; and claim 45.
Instant claim 3, part (3), recites the elected 31C8 antibody CDRs.
Instant SEQ ID NO: 73 in instant claim 5, part (i), and SEQ ID NO: 79 in instant claim 5, part (ii) contain the elected 31C8 antibody CDRs.
Instant SEQ ID NOS: 73 and 79 in instant claim 6, part (8), contain the elected 31C8 antibody CDRs.
Instant SEQ ID NO: 73 is contained in instant SEQ ID NO: 77 and instant SEQ ID NO: 79 is contained in instant SEQ ID NO: 81.
Instant SEQ ID NO: 77 in instant claim 7, part (i), and instant SEQ ID NO: 81 in instant claim 7, part (ii) contain the elected 31C8 antibody CDRS.
Instant SEQ ID NOS: 77 and 81 in instant claim 8, part (8), contain the elected 31 C8 antibody CDRs.
SEQ ID NO: 18 has sequence in common with instant SEQ ID NO: 77.
SEQ ID NO: 84 has sequence in common with instant SEQ ID NO: 81.
Each of the CDRs recited in instant claim 3, part (3), has at least one amino in common with the CDRs of Smith et al. Each of the VH/VL and heavy/light chains have sequence in common with the antibody sequences of Smith et al. See alignments below.
Alignment of SEQ ID NO: 18 (Qy) (CDRs of SEQ ID NOS: 40, 51, and 62 underlined) with instant SEQ ID NO: 77 (Db) (CDRs of SEQ ID NOS: 12, 17, and 22 underlined):
Query Match 93.1%; Score 2211; DB 1; Length 444;
Best Local Similarity 92.3%;
Matches 410; Conservative 14; Mismatches 20; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSIHWVRQAPGKGLEWMGGFGPEDGETIY 60
|||||||||:||||||:||:||| ||| : :|||:||||||||||| || |:|:|
Db 1 QVQLVQSGAKVKKPGATVKISCKASGYIFIDSEMHWVQQAPGKGLEWMGAIDPETGDTVY 60
Qy 61 AQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCTTEDSSGLFDYWGQGTLVTVSSAS 120
|:||:||||:| | |: |||||||||||||||||||| : | ||||||||||||||
Db 61 AKKFKGRVTITADKSSSTAYMELSSLRSEDTAVYYCTGSTTDYYFAYWGQGTLVTVSSAS 120
Qy 121 TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL 180
Qy 181 YSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLF 240
Qy 241 PPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVV 300
Qy 301 SVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQV 360
Qy 361 SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF 420
||||||||||||||:|||||||||||||||||||||||||||||||||||||||||||||
Db 361 SLTCLVKGFYPSDISVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF 420
Qy 421 SCSVMHEALHNHYTQKSLSLSPGK 444
||||||||||||||||||||||||
Db 421 SCSVMHEALHNHYTQKSLSLSPGK 444
Alignment of SEQ ID NO: 84 (Qy) (CDRs of SEQ ID NOS: 106, 117, and 128 underlined) with instant SEQ ID NO: 81 (Db) (CDRs of SEQ ID NOS: 27, 30, and 34 underlined):
Query Match 80.9%; Score 936.5; DB 1; Length 219;
Best Local Similarity 84.1%;
Matches 185; Conservative 8; Mismatches 26; Indels 1; Gaps 1;
Qy 1 DLVMTQSPDSLAVSPGERATINCKSSQSLLYSSNNKDYLAWYQQKPGQPPKLLIYWASTR 60
|: ||||| ||: | |:| || |:||:|||: || || |||||||: |||||| |
Db 1 DIQMTQSPSSLSASVGDRVTITCRSSKSLLH-SNGIIYLYWYQQKPGKAPKLLIYQLSNL 59
Qy 61 ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCHQYYNTPWTFGQGTKVEIKRTVAAPS 120
|||| ||| ||||||||||||||| || | ||| | |:||||||||||||||||||
Db 60 ASGVPSRFSSSGSGTDFTLTISSLQPEDFATYYCAQNLELPFTFGQGTKVEIKRTVAAPS 119
Qy 121 VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120 VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS 179
Qy 181 LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 220
||||||||||||||||||||||||||||||||||||||||
Db 180 LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
As such, antibody Ab1 of Smith et al. anticipates the antibodies of at least claim 3, part (3); claim 5; claim 6, part (8); claim 7; claim 8, part (8); claim 22; and claim 23, part (8). An Fab fragment of the Ab1 antibody of Smith et al. would also anticipate the antigen-binding fragments of the instant claims in view of the common sequences. See also instant claim 9. Smith et al. discloses pharmaceutical compositions. See at least paragraph [0391] with respect to instant claim 18. Antibody Ab1 binds to human and cynomolgus ST2. Antibody Ab1 inhibits ST2-IL33 interaction. See at least Tables 5 and 8 with respect to instant claim 10. Antibody Ab1 inhibited IL-5 secretion induced by IL33/ST2 on CD4+ T cells. See at least paragraph [0084] and Figure 3 with respect to instant claim 12. Bispecific antibodies and fusions of antibodies are disclosed. See at least paragraphs [0178 and 0189] with respect to instant claim 16.
Conclusion
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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