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 .
Status of Claims
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on October 30, 2025. Claims 1, 8, 56, 67 – 73, 76 – 80, 83, 85, 87 – 89, 91 – 92, and 85 – 96 are currently pending. Claims 56, and 70 – 72 have been amended and claims 97 – 100 have been newly added in the Applicant’s amendment filed 30 October, 2025. Claim 75 has been canceled in the Applicant’s amendment filed 30 October, 2025.
Applicant's election without traverse, in the reply filed 27 June, 2025 of Group III, claims 56, 67 – 73, 75, and 95, drawn to a CD8 targeting molecule; and the following election of Species, without traverse, is acknowledged:
Species (A): the ankyrin repeat protein comprises a sequence selected from the group consisting of Seq ID Nos. 1 – 28 (instant claim 72); and
Species (B): the target molecule comprises a lipid or lipid like component (instant claim 75).
Claims 1, 8, 76-– 80, 83, 85, 87 – 89, 96, 91, 92 and 96 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claim 67, 68, 69, 73, and 95 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement was previously made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 56, 70, 71, 72, and new claims 97 - 100 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed 1 June, 2022, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2020/087627, filed 22 December, 2022, which claims the benefit of PCT/EP2019087110, filed 27 December, 2019. A Certified translated copy of the PCT/EP2019087110 filed on 06/01/2022 is acknowledged.
Therefore, the earliest priority date is 27 December, 2019.
Maintained Objections/Rejections
Claim Rejection - 35 USC § 112(b)
Claim 99 is newly 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 is withdrawn.
Claim 99 is indefinite for the recitation of “the CD8 binding molecule is indirectly conjugated…..via an anionic polymer linked to the CD8 binding molecule” in lines 1-3. It is unclear which anionic polymer is being linked to the CD8 binding molecule. Further, the as-Filed Specification teaches that “by adding an anionic polymer to the core complex shielding the positive charge the transfection potential can be reduced” (Paragraph [0483]). Thus, it is unclear and indefinite what the anionic polymer is, and hence, the metes and bounds of the claim cannot be determined.
Claim Rejection - 35 USC § 103
Claim 56, and 70 – 71 remain rejected, and claims 97 - 100 are newly rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (hereinafter referred to as “Zhou”) (Zhou Q et al. T-cell receptor gene transfer exclusively to human CD8(+) cells enhances tumor cell killing. Blood. 2012 Nov 22;120(22):4334-42. doi: 10.1182/blood-2012-02-412973. Epub 2012 Aug 16. PMID: 22898597.), Munch et al. (hereinafter referred to as “Munch”) (Münch RC et al. DARPins: an efficient targeting domain for lentiviral vectors. Mol Ther. 2011 Apr;19(4):686-93. doi: 10.1038/mt.2010.298. Epub 2011 Jan 11. PMID: 21224833; PMCID: PMC3070099.), and in further view of Tamaskovic et al. (Tamaskovic et al. Designed Ankyrin Repeat Proteins (DARPins): From Research to Therapy. Methods in Enzymology, Volume 503, Chapter 5. 2012 Elsevier). This rejection has been modified necessitated by the response filed October 30, 2025.
Regarding claim 56, Zhou teaches a CD8-LV (lentiviral vectors) that delivers genes precisely and exclusively to CD8+ T cells, relying on high specificity of antibody-antigen recognition (Abstract) (interpreted as CD8 targeting molecule that targets immune effector cells). Zhou teaches that a scFv antibody fragment used as the targeting domain, and was generated from the broadly used mAb OKT8, which is specific for the α-chain of CD8 (pg. 4340, right column, first paragraph). Zhou teaches the scFV domain was not suited for the targeting domain (pg. 4340, right column, first paragraph).
Zhou does not specifically exemplify an ankyrin repeat protein, and that the CD8 binding molecule is conjugated to a cationic lipid, PEG-lipid, or cationic polymer (instant claim 56).
Regarding claim 56, Munch teaches a retargeting system for lentiviral vectors (LVs) (pg. 686, left column, first paragraph). Munch teaches that in these vectors pseudotyped with measles virus (MV) glycoproteins and by fusion to the MV-H protein as a targeting domain (scFv ) and as an alternative to scFv, a designed ankyrin repeat proteins (DARPins) can be selected to become high-affinity binders to any kind of target molecule and to replace the scFv (pg. 686, left column, first paragraph). Munch teaches that DARPins have no disulfide bonds and are very resistant to aggregation, and thus probably more compatible with the folding and assembly of integral membrane proteins (pg. 691, left column, first paragraph).
Regarding claims 70 and 71, Munch teaches DARPins consisting of two or of three ankyrin repeats between the capping repeats (pg. 690, right column, last paragraph).
The combined teaching of Zhou and Munch does not teach that the CD8 binding molecule is conjugated to a cationic lipid, PEG-lipid, or cationic polymer (instant claim 56).
Regarding claim 56, Tamaskovic teaches that DARPins can be easily PEGylated (pg. 108, second paragraph). Tamakovic teaches that the PEGylated DARPins accumulated more slowly and even better (pg. 108, last paragraph). Tamaskovic teaches that DARPins are highly stable and have robust folding, and hence, are being used in clinical trials (Abstract).
Regarding claims 97 – 100, Tamaskovic teaches “Click chemistry,” wherein PEGylation of DARPins at the N-terminus is performed (pg. 120, first paragraph). Regarding claim 99, as noted above, it is unclear which anionic polymer is being used. Under BRI, the examiner has interpreted claim 99 as the PEG is always linked to the CD8-binding molecule via an anionic polymer.
Therefore, in view of the benefits of the retargeting system for lentiviral vectors as evidenced by Munch, and the use of DARPins in clinical trials as taught by Tamaskovic, it would have been prima facia obvious for one ordinary skill in the art before the effective filing date of the claimed invention to replace the scFV antibody fragment in the CD8-LV, which is generated from the mAB OKT8, as evidenced by Zhou with the DARPins in the lentiviral vectors as evidenced by Munch, and add PEGylate the DARPin as taught by Tamaskovic, with a reasonable expectation of success in enhancing the targeting efficacy of the CD8-LVs, and allow for more accumulation of the CD8 binding molecule. It would have been prima facia obvious to combine the cited art because Zhou teaches the CD8-LVs that use scFVs, and teaches that scFV domain was not suited for the targeting domain, Munch teaches that the lentiviral vectors comprise designed ankyrin repeat proteins (DARPins) as an alternative to scFvs, which can be selected to become high-affinity binders to any kind of target molecule, and that DARPins have no disulfide bonds and are very resistant to aggregation, and Tamaskovic teaches that DARPins are easily PEGylated, yielding more and better accumulation of the DARPin.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
The ankyrin repeat protein comprises a sequence selected from the group consisting of SEQ ID Nos: 1 to 28 as recited in claim 72 appear to be free of prior art.
Response to Arguments as they apply to rejection of claims 58, 61, 150 – 153, under 35 USC § 103
Applicant’s arguments filed October 30, 2025 have been fully considered by they are not persuasive. Applicant essentially asserts that (a) the references to do not teach the limitations of amended claim 56.
Regarding (a), the claims are no longer rejected under Zhou and Munch, as claim 56 has been amended, and thus, the applicants’ arguments related to the combined teachings of Zhou and Munch are moot.
Conclusion
Claims 56, 70 – 71, and 97 - 100 are rejected.
Claim 72 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 extension fee 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/ Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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