DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment filed on July 13, 2026 is acknowledged.
Claims 18 and 19 have been canceled.
Claim 21 has been added.
Claims 1-17, 20, and 21 are pending.
Claims 7-10 and 12-17 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 23, 2026.
Claims 1-6, 11, 20, and newly added claim 21 are currently under consideration as they read on the elected invention.
3. In view of applicant’s amendment, following rejections are set forth.
4. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
5. Claims 2 and 21 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
A) Claim 2 recites a binding protein comprising an amino acid sequence of SEQ ID NO:1. Claim 2 is depended upon claim 1 which encompasses a binding protein comprising an amino acid sequence with at least 97% identity to SEQ ID NO:1 and wherein as compared to SEQ ID NO:1, one, two, three, or four of amino acid positions 73, 74, 82, 138, and 141 are substituted. Thus, claim 2 encompassing SEQ ID NO:1 does not further limit the subject matter of claim 1 which requires SQQ ID NO:1 to have at least one amino acid substitutions from 73, 74, 82, 138, or 141.
B) Claim 21 allows five substitutions in position 73, 74, 82, 138, and 141 in view of the recitation of “and/or” and the use of open transitional phrase of “has” with respect to the amino acid substitutions while independent claim 1 requires one, two, three or four amino acid substitutions.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
6. 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.
7. Claims 1, 3-6, 11, and 20 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 for the reasons of record.
The claims are drawn to a binding protein for huma Her2 comprising an amino acid sequence with at least 97% identity to SEQ ID NO:1, wherein the binding protein has a binding affinity for Her2 of less than 0.5 nM after 24h incubation in serum as determined by ELISA, and is stable at temperatures of at least 64oC, wherein as compared to SEQ ID NO:1, one, two, three or four of the amino acid positions 73, 74, 82, 138, and 141 are substituted.
The specification discloses that the ubiquitin dimer of amino acid sequence of SEQ ID NO:16 was mutated in 13 specific positions with specific amino acid residues producing SEQ ID NO:1. The specification further disclose Her2 binding proteins shown in Figure 1 (SEQ ID NOs: 1-14). SEQ ID NO:2-14 appears to be variants of SEQ ID NO:1, they differ from SEQ ID NO:1 in specific positions with specific amino acid residues.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that the claims have been amended to recite the positions that are substituted in SEQ ID NO:1. Applicant further provide sequence alignments of SEQ ID NOs: 1-14 and asserts that the alignments show amino acid positions 73, 74, 82, and 141 varies among SEQ ID NOs: 1-14, and thus assert that the SEQ ID NOs: 1-14 are representing species of the claimed genus. Therefore, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
While the amended claims recite the amino acid positions within SEQ ID NO:1 that can be substituted, the claims do not recite what amino acid residues can be used to substitute the pre-existing amino acids in positions 73, 74, 82, 138, and 141.
Independent claim 1 recites a binding protein for human Her2 comprising an amino acid sequence with at least 97% identity to SEQ ID NO:1, and compared to SEQ ID NO:1, one, two, three, or four amino acid positions 73, 74, 82, 138, and 141 are substituted. SEQ ID NO:1 consists of 152 amino acid residues. A protein with at least 97% identity to SEQ ID NO:1 would allow 4.56 amino acid residues that can be changed within SEQ ID NO:1 (152x3%=4.56), yet the claims only recite maximum of four substitutions are permitted with unidentified amino acid residues.
As shown by the SEQ ID NOs: 1-14 alignments provided by applicant, positions 73, 74, 82, 138, and 141 each occupies by a specific amino acid residue. Thus, it does not appear based upon the limited disclosure of the fourteen human Her2 binding proteins having specific amino acid sequences alone that Applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus of a human Her2 with at least 97% identity to SEQ ID NO:1 and compared to SEQ ID NO:1, one , two, three, or four amino acid positions 73, 74, 82, 138, and 141 are substituted in view of the limited number of species disclosed and the extensive variation permitted within the genus of binding protein.
As such, applicant’s arguments have not been found persuasive.
8. Claims 1, 3-6, 11, and 20 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 a binding protein for huma Her2 comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 1-14), does not reasonably provide enablement for more. 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/or use the invention commensurate in scope with these claims for the reasons of record.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that claim 1 has been amended to limit the mutations in positions 73, 74, 82, 138, and 141. Applicant asserts that SEQ ID NO:1 is 152 amino acids in length, a sequence at least 97% identical to SEQ ID NO:1 would mean up to 4 amino acids in SEQ ID NO:1 can be modified. Therefore, applicant asserts that the amended claims recite the positions to be mutated and thus satisfy the enablement requirement.
This is not found persuasive for following reasons:
Contrary to applicant’s assertion that up to 4 amino acids can be substituted, note that a sequence that is 97% identical to SEQ ID NO:1 (152 amino acids in length) would allow 4.56 amino acid changes which is more than 4 amino acids.
Further, while the amended claims recite the amino acid positions within SEQ ID NO:1 that can be substituted, the claims do not recite what amino acid residues can be used to substitute the pre-existing amino acids in positions 73, 74, 82, 138, and 141.
The specification discloses specific amino acid substitutions in specific positions of SEQ ID NO:1 for a binding protein for human Her2 with the recited binding affinity. However, there is insufficient objective evidence to show that the specific species of SEQ ID NOs: 1-14 having specific amino acid residues in positions 73, 74, 82, 138, and 141 can be extrapolated to enable substitutions in one, two, three, or four of amino acids in these positions with any or all amino acid residues.
Consequently, the experimentation left to those skilled in the art to determine which binding protein for human Her2 that is at least 97% identical to SEQ ID NO:1 and compared to SEQ ID NO:1, one, two, three, or four of amino acid of 73, 74, 82, 138, and 141 are substituted and the same function of having a binding affinity for Her2 of less than 0.5nM after 24h incubation in serum as determined by ELISA and is stable at temperatures of at least 64oC is unnecessarily, improperly, and extensive and undue.
Therefore, applicant’s arguments have not been found persuaive.
9. 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.
10. 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.
11. Newly added claim 21 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fiedler et al. (US 2018/0194819).
Fiedler et al. teach a binding protein that binds human Her2 and comprising amino acid sequence of SEQ ID NO:19 that is identical to the instant SEQ ID NO:1 except that position 73 is W, position 74 is Y, position 82 is T, position 138 is S, and position 141 is A (see sequence alignment below). As such, the reference teachings anticipate the instant claim 21.
Instant SEQ ID NO:1 (Qy) alignment to prior art protein:
RESULT 1
US-15-744-054A-19
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 19, US/15744054A
Patent No. 10584152
GENERAL INFORMATION
APPLICANT: Navigo Proteins GmbH
APPLICANT: Fiedler, Erik
APPLICANT: Meysing, Maren
TITLE OF INVENTION: NOVEL BINDING PROTEINS BASED ON DI-UBIQUITIN MUTEINS AND METHODS FOR GENERATION
FILE REFERENCE: 3073/10 PCT/US
CURRENT APPLICATION NUMBER: US/15/744,054A
CURRENT FILING DATE: 2018-01-11
PRIOR APPLICATION NUMBER: EP15177545.9
PRIOR FILING DATE: 2015-07-20
PRIOR APPLICATION NUMBER: PCT/EP2016/067216
PRIOR FILING DATE: 2016-07-19
NUMBER OF SEQ ID NOS: 45
SEQ ID NO 19
LENGTH: 152
TYPE: PRT
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: Artificially synthesized Affilin-142628
Query Match 96.5%; Score 749; Length 152;
Best Local Similarity 96.7%;
Matches 147; Conservative 1; Mismatches 4; Indels 0; Gaps 0;
Qy 1 MQIFVKTLTGKTITLEVEPSDTTENVKAKIQDKEGIPPDQQTLAFVGKQLEDGRTLSDYN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MQIFVKTLTGKTITLEVEPSDTTENVKAKIQDKEGIPPDQQTLAFVGKQLEDGRTLSDYN 60
Qy 61 IQKESTLWLYLTLRAAMRIFVKTHTGKTITLDVEPSDTIENVKAKIQDKEGIPPDQQRLI 120
|||||||||||| ||||||| ||||||||||||||||||||||||||||||||||||||
Db 61 IQKESTLWLYLTWYAAMRIFVTTHTGKTITLDVEPSDTIENVKAKIQDKEGIPPDQQRLI 120
Qy 121 WAGKQLEDGRTLSDYNIQEWSILHLVLRLRAA 152
||||||||||||||||| ||:|||||||||||
Db 121 WAGKQLEDGRTLSDYNISEWAILHLVLRLRAA 152
12. SEQ ID NO: 1-14 are free of the prior art.
13. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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