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 .
Claims 45-57 and 59-66 are pending.
Claims 45-57 and 59-66 are being acted upon in this Office Action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, 62/144,278, 62/151,943, 15/564,315, 16/720,176 fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The previously-filed applications 62/144,278, 62/151,943 do not disclose linker such as a cleavable linker, e.g., peptide linker, hydrazine, disulfide linkers, dipeptide linker that is cleaved by a lysosomal protease, e.g., cathepsin-B, dipeptide linker is a valine-citrulline linker, as in claims 46-52. The 62/144,278, 62/151,943, 15/564,315 and 16/720,176 do not teach the PEG has a molecular weight of about 500 Da as per claim 65 and an anti-GPIIb/IIIa scFv, an anti-VEGF-A scFv, and an anti-TNF-α scFv as per claim 66.
The invention of claims 45, 53-57, 59-63 was described in 62/144,278. The invention of claim 64 was described in 62/151,943.
Therefore for the purposes of applying prior art, the effective filing date of claims 45, 53-57, 59-63 is April 7, 2015, the date that 62/144,278 was filed. The effective filing date of claims 46-52 is Aril 7, 2016, the date that the application 15/564,315 was filed as a PCT. The effective filing date of claim 64 is April 23, 2015, the date of 62/151,943 was filed. The effective filing date of claims 65-66 is Oct 7, 2022, the date that application 17/961,761 was filed.
Should applicant disagree with the examiner’s factual determination above, applicant should point to evidence that shows that the invention of claims 45-66 is in fact described in one or more of the previously-filed applications.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 8, 2026 was filed after the mailing date of the Non-Final Office on Oct 10, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Rejection Withdrawn
The rejection of claim 50 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of the claim amendment.
The written description and enablement rejections of claims 45-64 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in view of the claim amendment.
The rejection of claims 45-64 under 35 U.S.C. 103 as being unpatentable over Bradbury et al (US20130039848, published February 14, 2013; PTO 1449) in view of Charles et al (US20140024776, published January 23, 2014; PTO 1449) and as evidenced by U.S. Pat. No. 7,754,681 (PTO 1449) is withdrawn in light of the claim amendment.
New grounds of Rejection Necessitated by claim amendment filed April 8, 2026
Claim rejections under - 35 U.S.C. 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claim 65 is 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is new matter.
The recitation of “PEG has a molecular weight of about 500 Da” in new claim 65 has no written support in the specification and the claim as originally. This is new matter.
Applicant is required to cancel claim 65 in response to this Office Action.
Double Patenting
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 45, 46, 53-57, 59-64 and 66 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3, 5-6, 8-12, 15-16 and 14-22 of U.S. Patent No. 11,559,591. Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims differ only in scope.
Issued claim 1 recites a nanoprobe created from an aminated nanoparticle, the nanoprobe comprising: a silica nanoparticle that comprises a polyethylene glycol (PEG) layer (species of polymer); a targeting agent generically conjugated to the silica nanoparticle via an amine group (aka instant linker) underneath the PEG layer; and a radiolabel conjugated to the silica nanoparticle via another amine group (aka instant linker) underneath the PEG layer, wherein the silica nanoparticle has a diameter no greater than 20 nanometers, which corresponds to instant claim 45.
The ’591 patent teaches that the targeting agent is covalently or non-covalently bounded to the nanoparticle via a linker, see col. 3, lines 31-35. The ‘591 patent teaches that the nanoparticle is coated with an organic polymer, e.g., polyethylene glycol (PEG), see col. 3, line 36-38.
Issued claim 2 recites the nanoprobe of claim 1, wherein the radiolabel comprises 89Zr, which is a radioisotope, corresponds to instant claim 45, 64.
Issued claim 5 recites the nanoprobe of claim 1, wherein the antibody fragment is in a range from about 5 kDa to about 25 kDa, which corresponds to instant claim 53.
Issued claim 6 recites the nanoprobe of claim 1, wherein the targeting agent comprises an antibody fragment, and wherein the antibody fragment is from about 20 kDa to about 45 kDa, which overlaps the instant claim 53.
Issued claim 8 recites the nanoprobe of claim 1, wherein the silica nanoparticle comprises a silica-based core and a silica shell surrounding at least a portion of the silica-based core, , which overlaps the instant claim 45.
Issued claim 9 recites the nanoprobe of claim 1, wherein the silica nanoparticle comprises a silica-based core and a fluorescent compound within the silica-based core, which corresponds to instant claim 54.
10. The nanoprobe of claim 1, wherein the targeting agent comprises VEGF.sub.121.
Issued claim 11 recites the nanoprobe of claim 1, wherein the targeting agent comprises an antibody fragment selected from the set consisting of a Fab fragment, a single chain variable fragment (scFv), and a single domain antibody (sdAb) fragment, which corresponds to instant claim 45.
Issued claim 12 recites the nanoprobe of claim 11, wherein the antibody fragment is a single chain variable fragment (scFv), which corresponds to instant claim 45.
Issued claim 15 recites the nanoprobe of claim 1, wherein the silica nanoparticle has a diameter no greater than 15 nanometers, which corresponds to instant claim 56.
Issued claim 16 recites the nanoprobe of claim 1, wherein the silica nanoparticle has a diameter in a range from 1 nm to 20 nm, which corresponds to instant claim 57.
Issued claim 17 recites the nanoprobe of claim 1, wherein the targeting agent comprises a member selected from the set consisting of anti-CEA scFv, anti-GPIIb/IIIa, anti-VEGF-A, anti-VEGF-R, and anti-TNF-α, which corresponds to instant claim 66.
Issued claim 18 recites the nanoprobe of claim 1, wherein the nanoprobe further comprises one or more imaging agents (genus), which corresponds to instant claim 59.
Issued claim 19 recites the nanoprobe of claim 18, wherein the one or more imaging agents comprise a PET or SPECT tracer, which corresponds to instant claim 60.
Issued claim 20 recites the nanoprobe of claim 19, wherein the PET or SPECT tracer comprises a member selected from the group consisting of .sup.89Zr, .sup.64Cu, .sup.18F fluorodeoxyglucose, .sup.177Lu, .sup.225At, and .sup.90Y (species), whereas instant claim 45 is generic with respect to the imaging agent or PET or SPECT tracer, which corresponds to instant claim 64.
Issued claim 21 recites the nanoprobe of claim 1, further comprising a therapeutic agent, which corresponds to instant claim 45.
Issued claim 22 recites the nanoprobe of claim 1, wherein the targeting agent comprises a recombinant antibody fragment, which encompasses the scFv of instant claim 45.
Claims 45-52 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3, 5-6, 8-12, 15-16 and 14-22 of U.S. Patent No. 11,559,591 in view of US20090220502 (Brandt hereafter, published September 3, 2009; PTO 892).
The claims of the ‘591 have been discussed supra.
The ‘591 patent does not teach the linker is cleavable linker as per claim 46, wherein the linker is a peptide linker as per claims 47 and 48, wherein the linker is cleaved by lysosomal proteases as per claim 49, wherein the lysosomal protease is cathepsin-B as per claim 50, wherein the linker is a dipeptide linker as per claim 51 and wherein the dipeptide linker is a valine-citrulline as per claim 52.
However, Brandt teaches various linkers such as dipeptide valine-citrulline (Val-Cit) linker which is cleaved within a lysosome by protease cathepsin-B, see para. [0245]. Brandt teaches that one advantage of using intracellular proteolytic release of the therapeutic agent is that the agent is typically attenuated when conjugated and the serum stabilities of the conjugates are typically high, see para. [0245].
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to have produced the claimed immunoconjugate by conjugating ‘591 patent’s scFv antibody to the nanoparticle via Brandt’s dipeptide linker valine-citrulline in order to release the payload within the lysosome.
The person of ordinary skill would have had a reasonable expectation of success to do so because Brandt teaches that such linker is cleaved by the thiol-dependent protease cathepsin-B, which is highly expressed in cancerous tissue.
One of ordinary skill in the art would have been motivated to do so because Brandt teaches that the conjugate is typically highly stable in serum and only release the payload within the lysosome, see para. [0245].
Claims 45-57, 59-64 and 66 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-15 and 20 of U.S. Patent No. 10,548,898. Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims differ only in scope.
Issued claim 1 recites an immunoconjugate comprising: a nanoparticle coated with an organic polymer; and an antibody fragment conjugated to the organic polymer-coated nanoparticle, wherein the nanoparticle has a diameter no greater than 20 nanometers, wherein the nanoparticle comprises a silica-based core and a silica shell surrounding at least a portion of the core, and wherein the antibody fragment is a single chain variable fragment (scFv), which corresponds to instant claim 45.
Issued claim 2 recites the immunoconjugate of claim 1, wherein the antibody fragment is covalently or non-covalently bonded to the nanoparticle via a linker or covalently or non-covalently bonded directly to the nanoparticle, or associated with the nanoparticle or a composition surrounding the nanoparticle, which corresponds to instant claim 45.
Issued claim 3 recites the immunoconjugate of claim 1, wherein the antibody fragment is from about 25 kDa to about 30 kDa, which corresponds to instant claim 53.
Issued claim 4 recites the immunoconjugate of claim 1, wherein the nanoparticle comprises a fluorescent compound within the core, which corresponds to instant claim 54.
Issued claim 5 recites the immunoconjugate of claim 1, wherein the nanoparticle has from one to ten antibody fragments attached thereto, which corresponds to instant claim 55.
Issued claim 6 recites thebimmunoconjugate of claim 1, wherein the nanoparticle has a diameter no greater than 15 nanometers, which corresponds to instant claim 45.
Issued claim 7 recites the immunoconjugate of claim 1, wherein the nanoparticle has a diameter in a range from 1 nm to 20 nm, which corresponds to instant claim, which corresponds to instant claim 57.
Issued claim 8 recites the immunoconjugate of claim 1, wherein the antibody fragment comprises anti-VEGF-A.
Issued claim 9 recites the immunoconjugate of claim 1, wherein the immunoconjugate comprises one or more imaging agents, which corresponds to instant claim 59.
Issued claim 10 recites the immunoconjugate of claim 9, wherein the one or more imaging agents comprise a PET tracer, which corresponds to instant claim 60.
Issued claim 11 recites the immunoconjugate of claim 9, wherein the one or more imaging agents comprise a fluorophore, which corresponds to instant claim 61.
Issued claim 12 recites the immunoconjugate of claim 1, further comprising a therapeutic agent, which corresponds to instant claim 45.
Issued claim 13 recites the immunoconjugate of claim 12, wherein the therapeutic agent comprises a chemotherapy drug, which corresponds to instant claims 45, 62.
Issued claim 14 recites the immunoconjugate of claim 12, wherein the therapeutic agent comprises a radioisotope, which corresponds to instant claims 45, 63.
Issued claim 15 recites the immunoconjugate of claim 14, wherein the radioisotope is a member selected from the group consisting of .sup.99mTc, .sup.111In, .sup.64Cu, .sup.67Ga, .sup.186Re, .sup.188Re, .sup.153Sm, .sup.177Lu, .sup.67Cu, .sup.123I, .sup.124I, .sup.125I, .sup.11C, .sup.13N, .sup.15O, .sup.18F, .sup.186Re, .sup.188Re, .sup.153Sm, .sup.166Ho, .sup.177Lu, .sup.149Pm, .sup.90Y, .sup.213Bi, .sup.103Pd, .sup.109Pd, .sup.159Gd, .sup.140La, .sup.198Au, .sup.199Au, .sup.169Yb, .sup.175Yb, .sup.165Dy, .sup.166Dy, .sup.67Cu, .sup.105Rh, .sup.111Ag, .sup.89Zr, .sup.225Ac, and .sup.192Ir, which corresponds to instant claim 64.
Issued claim 20 recites the immunoconjugate of claim 13, wherein the chemotherapy drug is a member selected from the group consisting of sorafenib, paclitaxel, docetaxel, MEK162, etoposide, lapatinib, nilotinib, crizotinib, fulvestrant, vemurafenib, bexorotene, and camptothecin (species), which corresponds to instant claims 45 and 62 (generic).
Regarding instant claims 46-52, the issued patent also teaches various linkers, a cleavable linker (e.g., peptide, hydrazine, or disulfide) is used. In certain embodiments, a noncleavable linker (e.g., thioether) is used. In certain embodiments, a peptide linker is selectively cleaved by lysosomal proteases (e.g., cathepsin-B). In certain embodiments, a valine-citrulline dipeptide linker is used, see col. 19, lines 9-15, in particular.
Regarding instant claim 66, the issued patent also teaches the antibody fragment comprises a member selected from the set consisting of anti-CEA scFv, anti-GPIIb/IIIa, anti-VEGF-A, and anti-TNFα, see col. 19, line 1-8, col. 4, line 1-4, in particular.
Claim Objection
Claim 64 is objected to because of the following informality: duplicate “77Lu” should be deleted.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHUONG HUYNH whose telephone number is (571)272-0846. The examiner can normally be reached on 9:00 a.m. to 6:30 p.m. The examiner can also be reached on alternate alternative Friday from 9:00 a.m. to 5:30 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Misook Yu, can be reached at 71-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
/PHUONG HUYNH/ Primary Examiner, Art Unit 1641
Prosecution Insights