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
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1, 3, 5, 6, 7, 10, 12, 14, 20, 22, 25, 28, 31, 33, 35, 37, 40, 41, 42, 44, 46, 74, 97) in the reply filed on February 05, 2025 is acknowledged. Claim 44 is omitted from the restriction requirement filed on 12/15/2024 and is included in elected group I.
Applicant’s provisional election of the following species in the response filed on 02/05/2025 is acknowledged: simeprevir as the small molecule, Seq ID NO: 1 as the target protein, Tn3 as the binding member, PRSIM_23 as the Tn3 PRSIM sequence, PRSIM_57 as the scFV sequence, a DBD-T and TRD-BM fusion protein, a viral protease. Election was made without traverse in the reply filed on February 05, 2025.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/IB2020/056657, filed 07/15/2020.
Applicant' s claim for the benefit of a prior-filed parent provisional application 62874025, filed on 07/15/2019, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is 07/15/2019.
Claims Status
Claims 3, 5-7, 20, 28, 31, and 33 are canceled. Claims 114-117 are newly added. New claim 114 and 116-117 are dependent on claims in elected Group I. New claim 115 is dependent on withdrawn claim 42 and thus is also considered withdrawn. Claims 12, 28, 31, 42, 51, 59, 71, 73, 90, 110 and 115 have been withdrawn from consideration as being drawn to non-elected subject matter. Claims 1, 10, 14, 22, 25, 35, 37, 40-41, 44, 46, 74, 97, 114 and 116-117 have been considered on the merits. All arguments have been considered.
Withdrawn Objections & Rejections
Applicant's response filed 12/22/2025 has been considered. Rejections and/or objections not reiterated from the previous Office action mailed 07/29/2025 are hereby withdrawn. Specifically, as discussed further below, the objections, rejections under 112, and rejections under 103 as recited in the previous action are withdrawn.
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application.
Claim Objections (new)
Regarding claim 1: part ii) recites “a a transposon Tn3 protein”. This is incorrect grammar. If the claims were amended to recite “[
Regarding claim 97: The claim recites “the small simeprevir” which is considered a typing mistake omitting the word “molecule”. If the claim was amended to recite “the small molecule simeprevir” the objection would be overcome.
Regarding claim 115: The claim status is incorrect. The claim status is recited as “(new)” however the claim is dependent on a withdrawn claim 42 and thus is withdrawn and should reflect the claim status “withdrawn”.
Claim Rejections - 35 USC § 112 (new)
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 1, 10, 14, 22, 25, 35, 37, 40-41, 44, 46, 74, 97, 114 and 116-117 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.
This is a new matter rejection.
Regarding claim 1: The claim has been amended to recite “a transposon Tn3 protein”.
The instant specification refers to Tn3 proteins as antibody mimetics derived from the third FnIII domain of human tenascin C (p29 ¶3) and discloses Seq ID NO: 134 as the sequence of a wild-type Tn3 protein (p29 ¶5).
The instant specification does not recite or refer to transposons or transposon derived proteins. Also, Applicant’s response fails to support the amendment of claim 1 that recites “a transposon Tn3 protein”. There is no evidence that a transposon Tn3 protein is equivalent to a Tn3 protein as recited in the instant claims or specification.
While Tn3 proteins associated with transposons are known in the art, they appear to be distinct from the Tn3 protein described in the instant invention. Nicolas et al (Microbiology Spectrum (2014) 3:4;1-32) teach the Tn3 family of transposons are a group of bacterial transposable elements and are a versatile system for mediating gene reassortment (abstract). Figure 3 of Nicolas teach the phylogenetic tree of the Tn3 family transposase proteins and figure 9 teaches the structure of the Tn3 family transposase protein. The Tn3 family transposase proteins comprise an N-terminal DNA-binding domain and a C-terminal catalytic domain (p15 Fig 9). Nicolas is silent on a binding function of a Tn3 transposon protein in which the Tn3 binds a target protein more tightly in the presence of simeprevir than binding either molecule alone.
Tn3 proteins that are similar to that described in the instant specification are also known in the art. Oganesyan et al (Structural Biology and Crystallization Communications(2013)f69;1-4; cited previously) teach Tn3 proteins are binding molecules based on the third fibronectin type III domain of human tenascin C which comprise three surface-exposed loops that can be engineered to achieve specific recognition of a cognate target (abstract). Oganesyan also teach that the more commonly used non-antibody scaffolds are based on the fibronectin type II domain (p1 ¶2). Oganesyan teach generating libraries of Tn3 variants to identify Tn3 proteins that bind a specific target protein (CD40L) (p1 para3).
Thus a transposon Tn3 protein as recited in the instant claim 1 and as described by the art is not supported by the instant disclosure and is therefore considered new matter (p29 ¶3).
If the claim were amended to recite “a tenascin Tn3 protein” the rejection as written would be overcome. This would overcome the rejection as written because the instant specification teaches Tn3 proteins are derived from the third fibronectin type III domain of human tenascin C (p29, ¶2).
In amended cases, subject matter not disclosed in the original application is sometimes added and a claim directed thereto. Such a claim is rejected on the ground that it recites elements without support in the original disclosure under 35 U.S.C. 112, first paragraph, Waldemar Link, GmbH & Co. v. Osteonics Corp. 32 F.3d 556, 559, 31 USPQ2d 1855, 1857 (Fed. Cir. 1994); In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981). See MPEP § 2163.06 - § 2163.07(b) for a discussion of the relationship of new matter to 35 U.S.C. 112, first paragraph.
New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to § 608.04(c). See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976) and MPEP § 2163.05 for guidance in determining whether the addition of specific percentages or compounds after a broader original disclosure constitutes new matter.
Applicant is required to cancel the new matter in the reply to this Office Action.
Claim 1 is rejected as failing to meet the requirement for written description. Note Claims 10, 14, 22, 25, 35, 37, 40-41, 44, 46, 74, 97, 114 and 116-117 also fail to meet the requirement for written description because they depend from rejected claim 1 and fail to cure the deficiencies of claim 1.
Claims 1, 10, 14, 22, 25, 35, 37, 40-41, 44, 46, 74, 97, 114 and 116-117 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.
This is a rejection as failing to comply with the written description requirement.
Regarding claim 1: The claim requires a transposon Tn3 protein binding member, wherein the binding member specifically binds to the T-SM complex at a higher affinity than it binds to both the target protein alone and the small molecule alone.
Thus the claim is drawn to a structure (protein) which possesses the function of binding to the T-SM complex at higher affinity than binding to either the target or small molecule alone.
Teachings of the instant specification
The instant specification teaches specific sequences of Tn3 proteins; Seq ID NOs: 134, 135 (p 29 ¶2; p30 ¶3). Seq ID NO 5-9 are also taught as Tn3 sequences (p30/31). The instant specification teaches sequences which can vary in the Tn3 protein (unnumbered Table p30/31) The instant specification further teaches Tn3 proteins can be subjected to directed evolution to generate binding members with high affinity for targets of interest (p30 ¶2).
The instant specification teaches Tn3 sequences isolated from a phage display selection to select for Tn3 proteins with affinity for the complex of NS3/4A bound with simeprevir (p62 ¶2/3). Table 1 (p80) teach Tn3 proteins and fold change of binding with the target protein in the presence of simeprevir. Table 1 teach 25 structures of Tn3 proteins (PRSIM23-41 and 43-50) which bind the target protein with greater than 20 fold affinity in the presence of simeprevir (p80/81). Table 2 teach PRSIM_23, 32, 33, 36 and 47 bind the target protein with specificity (p83).
Teachings of the art
Nicolas et al (Microbiology Spectrum (2014) 3:4;1-32) teach the Tn3 family of transposons are a group of bacterial transposable elements and are a versatile system for mediating gene reassortment (abstract). Figure 3 of Nicolas teach the phylogenetic tree of ~57 Tn3 family transposase proteins and figure 9 teaches the structure of the Tn3 family transposase protein (p6/7; Fig 3). The Tn3 family transposase proteins comprise an N-terminal DNA-binding domain and a C-terminal catalytic domain (p15 Fig 9). Nicolas is silent on the ability the Tn3 transposon proteins ability to function by binding a target protein/small molecule complex with higher affinity than a target protein or small molecule individually.
Dias et al (BMC (2017) 18:5;1-12) teach protein function is determined by how proteins interact with small-molecules, DNA/RNA, proteins and other ligands (p2 col1 ¶1). Dias further teach that while protein-ligand affinity can be predicted directly from physical chemistry principles, the most effective approaches are usually “trained” using large databases of structural complexes with associated experimentally-determined binding affinities (p2 col1 ¶1). Thus Dias teach that protein binding affinity is unpredictable and requires trial and error experimentation to determine accurate protein-ligand affinities.
Conclusion
As discussed supra, the instant specification teaches ~25 specific structures that possess the claimed binding function. However, the instant specification does not provide guidance for identification of all structures that can achieve the function as claimed and the examples of structures taught by the instant specification are too few to constitute a representative sample of all structures that could bind the T-SM complex at a higher affinity than the T or SM molecule alone.
Furthermore, in view of the art, predicting the binding function of a Tn3 protein requires trial and error experimentation because Dias teach that binding affinity is unpredictable and the most effective approaches to predicting affinity requires large databases of experimentally determined binding affinities.
Furthermore, the instant specification provides no guidance as to key structural components that are required for Tn3 proteins to perform the claimed function, and the art does not provide a remedy.
Claim 1 is rejected as failing to meet the requirement for written description. Note Claims 10, 14, 35, 37, 40-41, 44, 46, 74, 97, 114 and 116-117 also fail to meet the requirement for written description because they depend from rejected claim 1 and fail to cure the deficiencies of claim 1.
Response to Arguments
The responses are directed to the Arguments filed 12/22/2025.
Regarding Arguments directed to the claim objections:
Applicant’s amendment of the claims to recite “a transposon Tn3 protein” overcomes the objection as written. The objection is withdrawn.
Regarding Arguments directed to 35 USC § 112(a):
Applicant's amendment of the claims to recite “a target protein derived from an HCV NS3/4A protease having an amino acid sequence at least 90% identity to SEO ID NO: 1” overcomes the rejection directed to the “viral protease derived target protein”.
Applicant's amendment of claim 1 to recite “simeprevir” overcomes the rejection directed to the “viral protease inhibitor”.
Applicant's amendment of the claims to recite “a transposon Tn3 protein binding member” overcomes the rejection directed to the “binding member”.
The rejection is withdrawn.
Regarding Arguments directed to 35 USC § 112(b):
The rejection heading was included in the previous action in error and is withdrawn.
Regarding Arguments directed to 35 USC § 103:
The amendments to the claims overcome the rejection and the rejection is withdrawn. The claims have been amended to recite “a transposon Tn3 protein binding member”. Transposon Tn3 proteins which bind proteins/small molecule complexes with higher affinity than the protein and small molecule individually are not found in the art and thus the rejection is withdrawn.
Furthermore, claim 1 is amended to require a protease having an amino acid sequence at least 90% identity to Seq ID NO: 1.
Conclusion
No claims are allowed.
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.
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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