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 .
2. Applicant’s amendment filed on 03/30/2026 is acknowledged.
3. Claims 1, 5-6, 8-17 and 19-28 are pending.
4. Claims 10-11, 16-17, 19-20 and 22-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/18/2024 and 10/07/2024.
5. The Examiner would like to make clear on the record that the claims only read on a Fab with the recited factors being fused at the C-terminal end of the VH domain and not to the C-terminal end of the Fab heavy chain. As such, the factors recited in the claims are only located between the VH and the CH1. As such, the Examiner is extending the search to the additional previously withdrawn species of claims 21 and 24-26.
6. Claims 1, 4-6, 8-9, 12-15, 21 and 24-28 are under consideration for their full scope.
7. The following rejections are necessitated by the amendment filed on 03/30/2026.
8. 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.
9. Claims 21 and 24-25 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.
A. Claim 21 recites the limitation "the cryptochrome" in line 1. There is insufficient antecedent basis for this limitation in the claim.
B. Claim 24 recites “an anti-GPCR antibody” and this term is unclear and indefinite because GPCR is not a specific molecule as evidenced by the specification on pages 4-5. It is also unclear what is encompassed by an anti-GPCR agonist antibody. The scope of this recitation cannot be ascertained and can change over time.
C. Claim 25 recites “an anti-RTK antibody” and this term is unclear and indefinite because RTK is not a specific molecule as evidenced by the specification on page 9. It is also unclear what is encompassed by an anti-RTK agonistic antibody. The scope of this recitation cannot be ascertained and can change over time.
Correction is required.
10. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
11. Claims 1, 4-6, 8-9, 12-15, 21 and 24-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/856,303 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-14 and 20 of 18/856,303 are directed to a light-controlled molecular system comprising: a. at least one recombinant protein comprising a variable domain of an antibody that is fused at its c-terminal end to a compound that interacts with a photoactivable agent in a light-dependent manner, and b. at least one tumor-antigen targeting antibody that is fused at its c-terminal end to the photoactivable agent of claim 1; the at least one recombinant protein comprises a Fab fragment wherein the VH domain of the Fab fragment is fused at its c-terminal end to a the compound that can interact with a photoactivable agent in a light-dependent manner of claim 2; wherein the Fab fragment is from an agonistic antibody specific for a receptor of an immune cell of claim 3; wherein the recombinant protein comprises a single domain antibody or an agonistic single domain antibody of claim 4; wherein the agonistic antibody is specific for a TCR or a costimulatory receptor selected from the group consisting of CD134 (OX40), CD137 (4-1BB), CD28, GITR, CD27, CD70,ICOS, RANKL, TNFRSF25 (DR3), CD258 (LIGHT), CD40 and HVEM of claim 5; wherein the agonistic antibody is specific for TCR Beta or CD3epsilon of claim 6; wherein the at least one tumor-antigen targeting antibody is a single-domain antibody or an antibody mimetic of claim 7; wherein the compound that the at least one tumor-antigen targeting antibody is the photoreceptor protein of claim 8; wherein the factor is selected from the group consisting of PIF1, PIF2, PIF3, PIF4, PIF5, PIF6, and PIF7 of claim 9; wherein the factor comprises an amino acid sequence that has at least 90% 4f identity with the amino acid sequence as set forth in SEQ ID NO:1 of claim 10; wherein the photoreceptor protein is selected from the group consisting of Phytochrome A (PhyA), Phytochrome B (PhyB), Phytochrome C (PhyC),Phytochrome D (PhyD), and Phytochrome E (PhyE) of claim 11; wherein the photoreceptor protein comprises an amino acid sequence that has at least 90% identity with the amino acid sequence as set forth in SEQ ID NO:2 or SEQ ID NO:3 of claim 12; wherein the compound that interacts with a photoactivable agent in a light-dependent manner is the photoactivable agent fused to the it least one tumor-antigen targeting antibody, wherein the photoactivable agent dimerizes in a light-dependent manner of claim 13; wherein the photactivable agent is a photoreceptor protein or a photoisomerizable compound of claim 14; and wherein the single-domain antibody is an anti-TRP-1 single domain antibody or an anti-EpCAM single domain antibody of claim 20.
Reference SEQ ID NO:1 is 100% sequence identical to instant SEQ ID NO:1.
The reference teachings anticipate the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s arguments filed on 03/30/2026 have been fully considered, but are not found persuasive.
Applicant argues
“Applicant will address this rejection when the final outcome of the claims in the present or copending application is determined. It is reminded that MPEP 804 requires that "[i]f a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earliest effective U.S. filing date (taking into account any benefit under 35 U.S.C. 120, 121, 365(c), or 386(c)) with respect to the conflicting claims) compared to the reference application(s), the examiner should withdraw the rejection in the application having the earliest effective U.S. filing date and permit that application to issue as a patent". The present application has an earlier effective filing date as compared to 18/856,303.”
It is the Examiner’s position that the rejection stands for reasons of record.
12. 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.
13. 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.
14. Claim 28 is rejected under 35 U.S.C. 103 as obvious over WO 2017/135568 (PTO-892 mailed on 12/31/2025; Reference N) as evidenced by the translation in U.S. Patent Application Publication 2019/0092839 (PTO-892 mailed on 12/31/2025; Reference A).
WO 2017/135568 teaches a fusion protein comprising a VL Fab fragment fused to phytochrome B. The reference further teaches a fusion protein comprising a VH Fab fragment is fused to phytochrome interacting factor 6 (PIF6) which forms a dimer with phytochrome B upon stimulation, wherein the VH and VL Fab fragments when bound together have antigen-binding capacity by dimerizing of the Phytochrome interacting factor 6 and phytochrome B induced by light. (In particular, claims, whole document). The reference teaches that the Fab can be designed bind to any antigen and that the composition can be used to treat disease that occur due to the overexpression of an antigen wherein the fusion proteins are used to detect and inactivate antigens in a cell by inhibiting specific proteins (In particular paragraph [0099] referring to U.S. Patent Application Publication 2019/0092839)
The following paragraphs in U.S. Patent Application Publication 2019/0092839 teach:
[0092] The light-induced dimerization protein may be a light-induced heterodimerization protein and/or light-induced homodimerization protein. The light- induced heterodimerization protein may be cryptochrome-interacting basic-helix-loop- helix protein (CIB), N-terminal domain of CIB (CIBN), phytochrome (Phy), phytochrome interacting factor (PIF), Flavin-binding, Kelch repeat, F-box 1 (FKF1), GIGANTEA, chryptochrome (CRY), phytolyase homolgous region (PHR), nMag, or pMag; and the light-induced homodimerization protein may be CRY or PHR. Conventionally, CRY or PHR is known to form homodimers irrespective of light irradiation, but the present inventors have discovered that CRY or PHR forms a homodimer by light irradiation. Therefore, CRY or PHR is a protein which not only forms heterodimers by light irradiation, but also forms homodimers by light irradiation.
[0093] In the above fusion protein, the light-induced dimerization protein may be a light-induced heterodimerization protein or light-induced homodimerization protein, and the light-induced heterodimerization protein may be CIB, CIBN, PhyB, PIF, FKF1, GIGANTEA, CRY, PHR, nMag, or pMag.
[0094] In the above fusion protein, the partner protein is a protein which can form a heterodimer with the light-induced heterodimerization protein by light irradiation, and the partner protein may be CIB, CIBN, PhyB, PIF6, FKF1, GIGANTEA, CRY, PHR, nMag, or pMag. The partner protein may be CRY or PHR when the light-induced heterodimerization protein is CIB or CIBN; the partner protein may be PIF when the light- induced heterodimerization protein is PhyB; the partner protein may be GIGANTEA when the light-induced heterodimerization protein is FKF1, whereas the partner protein may be CIB or CIBN when the light-induced heterodimerization protein is CRY or PHR; the partner protein may be PhyB when the light-induced heterodimerization protein is PIF; the partner protein may be FKF1 when the light-induced heterodimerization protein is GIGANTEA; the partner protein may be pMag when the light-induced heterodimerization protein is nMag, whereas the partner protein may be nMag when the light-induced heterodimerization protein is pMag. Meanwhile, the PIF may be PIF3 or PIF6.
[0095] In the above fusion protein, the light-induced heterodimerization protein or partner protein can form a homodimer by light irradiation. In this case, the light-induced dimerization protein or partner protein that can form a homodimer by light irradiation may be CRY or PHR.
[00101] In accordance with another aspect of the present disclosure, the provided is a method for activating the antibody analogue, the method including: introducing a first fusion protein comprising an inactive first fragment of an antibody analogue is fused to a stimulus-induced dimerization protein, and a second fusion protein comprising an inactive second fragment of an antibody analogue is fused to a stimulus-induced dimerization partner protein which forms a dimer with the stimulus-induced dimerization protein upon stimulation, wherein the inactive second fragment recovers antigen-binding capacity when bound to the inactive first fragment by dimerizing of the stimulus-induced dimerization protein and the stimulus-induced dimerization partner protein induced by a stimulus to a subject, tissue, or cell; and applying the stimulus to the subject, tissue or cell, wherein the stimulus induces dimerization of the stimulus-induced dimerization protein and the stimulus-induced dimerization partner protein.
[00103] In the above method, the antibody analogue may be Fab, F(ab')2, Fab', VHH, monobody, VLR, Affibody, Affilin, Affimer, Affitin, Alphabody, Anticlin, Avimer, DARpin, Fynomoer, or Kunitz domain peptide.
[00112] In the above case, the partner protein is a protein which can form a heterodimer with the light-induced heterodimerization protein by light irradiation, and the partner protein may be CIB, CIBN, PhyB, PIF6, FKF1, GIGANTEA, CRY, PHR, nMag, or pMag. The partner protein may be CRY or PHR when the light-induced heterodimerization protein is CIB or CIBN; the partner protein may be PIF when the light-induced heterodimerization protein is PhyB; the partner protein may be GIGANTEA when the light-induced heterodimerization protein is FKF1, whereas the partner protein may be CIB or CIBN when the light-induced heterodimerization protein is CRY or PHR; the partner protein may be PhyB when the light-induced heterodimerization protein is PIF; the partner protein may be FKF1 when the light-induced heterodimerization protein is GIGANTEA; the partner protein may be pMag when the light-induced heterodimerization protein is nMag, whereas the partner protein may be nMag when the light-induced heterodimerization protein is pMag. Meanwhile, the PIF may be PIF3 or PIF6.
[00113] In the above case, the light-induced heterodimerization protein or partner protein can form a homodimer by light irradiation. In particular, the light-induced dimerization protein or partner protein that can form a homodimer by light irradiation may be CRY or PHR.
[00114] In the above case, the light-induced heterodimerization protein or partner protein can form a homodimer by light irradiation. In particular, the light-induced heterodimerization protein or partner protein that can form a homodimer by light irradiation may be CRY or PHR.
[0085] In the fusion protein, the antibody analogue is Fab,
[0062] As used herein, the term "CRY" refers to a chryptochrome protein, and a representative example is the CRY2 of Arabidopsis thaliana (GenBank No.: NM_100320).
[0063] As used herein, the term "PHR"", indicating the N-terminal region of the CRY, refers to a phytolyase homolgous region that interacts with the CIB or CIBN upon light irradiation (Kennedy et al., Nat. Methods, 7(12): 973-975, 2010). [0064] As used herein, the term "Phy" refers to a phytochrome protein, and representative examples include PhyA (GenBank No.: NM_001123784) and PhyB (GenBank No.: NM_127435) of Arabidopsis thaliana. Phy is known to interact with a phytochrome interacting factor (PIF) (Min et al., Nature, 400: 781-784, 1999). [0065] As used herein, the term "PIF" refers to a phytochrome interacting factor, and representative examples include PIF1 (GenBank No.: NM_001202630), PIF3 (GenBank No.: NM_179295), PIF4 (GenBank No.: NM_180050), PIF5 (GenBank No.: NM_180690), PIF6 (GenBank No.: NM_001203231), and PIF7 (GenBank No.: NM_125520) of Arabidopsis thaliana.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
15. Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/121806 (PTO-892 mailed on 12/31/2025; Reference O) in view of WO 2017/135568 (PTO-892 mailed on 12/31/2025; Reference N) as evidenced by the translation in U.S. Patent Application Publication 2019/0092839 (PTO-892 mailed on 12/31/2025; Reference A).
WO 2014/121806 teaches a kit comprising: (a) a first protein that is coupled to a capture reagent; and (b) a second protein coupled to a suitable first binding domain, and the kit further comprises either a protein of interest (POI) that is coupled to a suitable second binding domain or a protein binding molecule that is coupled to a suitable second binding domain, wherein said first and second binding domain bind to each other; wherein said first and second proteins can bind to each other in a light- dependent manner; wherein (i) one of said first and second proteins is selected from the group consisting of Phytochrome A (PhyA), Phytochrome B (PhyB), Phytochrome C (PhyC), Phytochrome D (PhyD), and Phytochrome E (PhyE); and (ii) the other of said first and second proteins is selected from the group consisting of FHL, FHY1 , Phytochrome interacting factor 1 (PIF1 ), PIF3, PIF4, PIF5, PIF6, PIF7, PIF8, COP1 , CRY1 , FyPP, IAA17, PslAA4, NDPK2, PAPP5, PIL2, PIL5, and PIL6 (In particular, claims, whole document). The reference teaches that the capture reagent to be used in the context of the present invention is not particularly limited and suitable capture reagents are known in the art. In a preferred embodiment, the capture reagent is selected from the group consisting of magnetic beads and agarose. In a preferred embodiment, the first protein is coupled to the capture reagent via the interaction between biotin and streptavidin, i.e. the first protein is biotinylated, preferably via a biotinylatable tag (such as e.g. AVITag™) that is coupled thereto, and the capture reagent is coupled to streptavidin. Methods for the biotinylation of proteins, as well as methods for the coupling of streptavidin to a capture reagent are known in the art. The binding domains to be used in the context of the present invention are complementary binding domains, i.e. the first and second binding domains bind to each other. Suitable binding domains are not particularly limited and are known in the art. In a particular embodiment, one binding domain is a domain binding the Fc portion of an antibody, and the other, complementary binding domain is the Fc portion of an antibody. A specific example of a domain binding the Fc portion of an antibody is the ZZ domain of protein A derived from Staphylococcus aureus which binds to the Fc portion of immunoglobulin G (IgG).
In another particular embodiment, the above second binding domain is not coupled directly to the POI, but to a protein binding molecule, wherein said at least one POI is bound to said protein binding molecule. In an alternative embodiment, the protein binding molecule is directly coupled to said second protein. Suitable protein binding molecules are not particularly limited and are known in the art. Respective examples include antibodies, antibody fragments, aptamers, Affibodies®, i.e. artificial antigen-binding peptides derived from Staphylococcus aureus Protein A, and DARPINs (Designed Ankyrin Repeat Proteins), i.e. artificial antigen-binding proteins.
The claimed invention differs from the prior art in the recitation of a Fab fragment wherein the VH domain of the Fab fragment is fused at its c-terminal end to PIF of claim 28.
WO 2017/135568 as evidenced by the translation in U.S. Patent Application Publication 2019/0092839 has been discussed supra.
It would have been obvious to one of ordinary skill in the art at the time of invention to have used binding proteins that are Fab fragments wherein the VH domain of the Fab fragment is fused at its C-terminal end to PIF6 because WO 2017/135568 teaches a fusion protein comprising a VL Fab fragment fused to phytochrome B. The reference further teaches a fusion protein comprising a VH Fab fragment is fused to phytochrome interacting factor 6 (PIF6) which forms a dimer with phytochrome B upon stimulation, wherein the VH and VL Fab fragments when bound together have antigen-binding capacity by dimerizing of the Phytochrome interacting factor 6 and phytochrome B induced by light. (In particular, claims, whole document).
It would have been obvious to have combined the references which are both directed to the same light induced fusion proteins comprising antibody fragments which bind together for activation upon being stimulated by light through use of phytochrome B and PIF6 and other light activated protein sets.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
16. No claim is allowed.
17. 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 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 date of this final action.
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (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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June 25, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
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