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 .
Claim objections
Claim 18 is objected to as missing a period. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-5 and 8-23 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. The term genus “enzyme sensitive linker” and what species fall within this genus is not adequately described in the application. Although the term “enzyme sensitive liners” is recited in paragraph 72 of the specification : “enzyme sensitive linkers, for example, where drug release is catalyzed by proteases,” this does describe what linkers are enzyme sensitive linkers within the claimed genus, and therefore does not describe what species fall under this genus. Therefore, the artisan would not accept that applicant had possession of the genus and the species that fall within the claimed genus at the time the invention was filed.
Claim Rejections - 35 USC § 112
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.
Claims 1-5 and 8-23 are 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. Regarding claim 1, it’s unclear what attributes or characteristics a linker needs to have in order to be considered an enzyme-sensitive linker. This unclear and there is nothing in the application that clarifies this. Further regarding claim 18, it’s unclear if an “analog” is an analog by structure or by properties. It’s also unclear how far removed an analog can be from its parent structure or parent properties and still be considered an analog and not an entirely new compound all together. It’s further unclear what it means to be a pharmaceutical or therapeutic equivalent of dasatinib or gefitinib, and how similar the pharmaceutical or therapeutic needs to be to be considered a pharmaceuetical or therapeutic equivalent. It’s further unclear what it means for dasatinib or geftitinib to be modified to provide attachment to the linker moiety without perturbing underlying chemical structure of an active binding site of the drug moiety. It’s unclear what underlying chemical structure is being claimed, and what constitutes the underlying structure as being perturbed or not perturbed. Further regarding claim 20, there is no description of how to treat the genus of “cancer” comprising administering to a subject the NDC of claim 1. Cancer is difficult to treat. There are no procedures or treatment protocols in the application that describe how cancer is treated with the present invention which does not include an anti-cancer agent. Further, the application does not describe how to treat cancer using the claimed method over the scope of cancer. There are more than 200 distinct types of cancer, and each behaves differently depending on the tissue of origin and the specific driver mutations. A single agent designed to shut down one biological pathway will fail against another cancer that relies on completely different mechanisms. For example, a drug that effectively blocks hormone receptors in a specific breast cancer subtype will have zero impact on a blood cancer like leukemia. Cancers are not uniform. Even within a single tumor in one patient, there is massive cellular diversity (heterogeneity). A tumor contains multiple distinct sub-clones, each carrying different genetic mutations. If a patient is treated with a single targeted agent, it may successfully eliminate 95% of the tumor cells, but the remaining 5% will be inherently resistant, surviving to multiply and cause a relapse. It is currently not possible to treat cancer across the scope of cancer with a single agent because cancer is not a single disease, but an umbrella term for hundreds of distinct biological conditions
Claim Rejections - 35 USC § 103
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 8-11, 13, 15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2013192609 to Wiesner (document already in record) in view of Zhong (International Journal of Oncology, 2013; document already in record). Wiesner teaches nanoparticles comprising a nanoparticle drug conjugate comprising: a nanoparticle; a linker moiety (paragraph 54); and a drug moiety (paragraph 74), wherein the nanoparticle is coated with polyethylene glycol (an organic polymer) (paragraph 12), and wherein the drug moiety and linker moiety form a cleavable linker-drug construct that is covalently linked to the nanoparticle (paragraph 54). The particle further comprises a fluorescent compound, such as Cy5.5 (paragraph 53). The linker may be a bifunctionalized linear polyethylene glycol (PEG) comprising a N-hydroxysuccinimide and a maleimide moiety and in one embodiment, cRGD peptide is conjugated to a silane-PEG-maleimide linker via cysteinemaleimide (paragraph 169). The particle comprises a silica-based core and a silica shell surrounding the core (paragraph 89). A preferable average particle size is 3 nm to 12 nm (paragraph 45). The prodrug formulation of Wiesner may be used to treat cancer (paragraph 169).
Wiesner fails to teach an enzyme sensitive linker.
Zhong discloses enzyme sensitive biocleavable linkers conforming to instant claim 3 comprising a peptide and a biodegradable spacer and the dipeptide linker phenylalanine-lysine (Phe-Lys) (page 375; Table 1 ). These linkers may be used in prodrugs to treat cancer by tethering the active agent to a polymeric support (abstract; page 372, page 1; Figure 2).
It would have been obvious to one of ordinary skill in the art at the time the instant invention was filed to use a linker moiety of Zhong as the linker of Wiesner. The motivations for this is that Zhong teaches the efficacy of using its linkers to attach drugs to supports for enzyme mediated release. The expectation of success is high, as Wiesner teaches use of its prodrug formulation to treat cancer, and Zhong teaches its linkers may be used to treat cancer.
Claims 1-5, 8-13, 15, and 17-23 are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over WO 2013192609 to Wiesner (document already in record) in view of Zhong (International Journal of Oncology, 2013; document already in record) in further view of WO 2006099445 to Sengupta (document already in record). The relevant portions of Wiesner and Zhong are given above.
Wiesner and Zhong fail to teach a radiolabel.
Sengupta teaches incorporation of radiolabels into nanoparticles for tracing the nanoparticle in biological applications (Fig. 1; claims).
It would have been obvious to one of ordinary skill in the art at the time the
instant invention was filed to use a radiolabel as the fluorescent tag of Sengupta. The
rationale for this is that the art teaches the incorporation of radiolabels in nanoparticles
for tracing the nanoparticle in biological applications.
Claims 1-4, 8-11, 13, and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2013192609 to Wiesner (document already in record) in view of Zhong (International Journal of Oncology, 2013; document already in record) in further view of Doronina (Bioconjugate Chemistry, 2008; document already in record). The relevant portions of Wiesnerand Zhong are given above.
Wiesner and Zhong fail to teach a linker comprising a paminobenzyloxycarbamate group.
Doronina teaches the efficacy of linkers comprising p-aminobenzyloxycarbamate
to attach drugs to supports for biodegradable release (page 1961; Fig. 1 ).
It would have been obvious to one of ordinary skill in the art at the time the
instant invention was filed to use a p-aminobenzyloxycarbamate group as a
component in the PEG linkers of Wiesner. The rationale for this is that the art teaches
the efficacy of linkers comprising p-aminobenzyloxycarbamate to attach drugs to
supports for biodegradable release (.
Claims 1-5, 7-11, 13-15, and 17-19 are rejected under 35 U.S.C. 103 as being
unpatentable over WO 2013192609 to Wiesner (document already in record) in view of Zhong (document already in record) in further view of WO2011084620 to Farokhzad (document already in record). The relevant portions of Wiesner and Zhong are given above.
Wiesner and Zhong fail to teach tyrosine kinase inhibitors or gefitinib as drug
moieties.
Farokhzad teaches administration of a tyrosine kinase inhibitor such as gefitinib
(an anticancer agent) attached to a nanoparticle through a conjugated polymer
(abstract; page 3, lines 14-17; page 21, lines 30-31; claim 15).
It would have been obvious to one of ordinary skill in the art at the time the
instant invention was filed to incorporate a tyrosine kinase inhibitor such as gefitinib as
the drug moiety of Wiesner. The rationale for this is that Wiesner teaches incorporation
of anticancer agents (paragraph 59), and tyrosine kinase inhibitors such as gefitinib are
known anticancer agents. Incorporation of a tyrosine kinase inhibitor such as gefitinib
as the anticancer agent of Wiesner is no more than using an art recognized agent for its
art recognized purpose.
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 obviousness-type 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); 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 conflicting 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.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
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 obviousness-type 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); 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 conflicting 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.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-5 and 8-23 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 1-34 of U.S. Patent 10111963. Although the conflicting claims are not identical, they are not patentably distinct from each other because the patent claims, which recites nanoparticle drug conjugate (NDC) comprising: a non-mesoporous nanoparticle; an enzyme sensitive linker moiety; and a drug moiety, wherein the non-mesoporous nanoparticle comprises a silica-based core and a silica shell surrounding a least a portion of the core, wherein the NDC has a diameter less than 10 nm, wherein the non-mesoporous nanoparticle is coated with an organic polymer, and wherein the drug moiety and enzyme sensitive linker moiety form a cleavable linker-drug construct that is covalently linked to the non-mesoporous nanoparticle and that facilitates enzyme catalyzed drug release (patent claim 1), wherein the enzyme sensitive linker moiety comprises one or more amino acids (patent claim 2), wherein the enzyme sensitive linker moiety comprises (Amino-(spacer)x)y-peptide or (spacer)z-peptide, wherein the spacer has from 2 to 50 atoms,wherein x is an integer from 1 to 5, wherein y is an integer from 1 to 5, wherein z is an integer from 5 to 15, and wherein the enzyme sensitive linker moiety comprises a degradable moiety between the enzyme sensitive linker moiety and the drug moiety (patent claim 3), wherein the enzyme sensitive linker moiety comprises a spacer between a peptide and the drug moiety (patent claim 4),comprising a fluorescent compound (patent claim 5), further comprising a radiolabel (patent claim 5), wherein the enzyme sensitive linker moiety is capable of undergoing hydrolysis at a C-terminal end upon protease binding, thereby releasing the drug moiety from the non-mesoporous nanoparticle (patent claim 4), wherein the drug moiety comprises a receptor tyrosine kinase (RTK) inhibitor (patent claim 8), further comprising from 1 to 20 targeting moieties, wherein the targeting moieties bind to receptors on tumor cells (patent claim 9), wherein the NDC is a theranostic (patent claim 10), wherein the fluorescent compound is Cy5.5 (patent claim 11), wherein the drug moiety is attached to the radiolabel (patent claim 12), wherein the one or more amino acids include a peptide or polypeptide, and include 1 to 10 amino acids, the (Amino-(spacer)x)y-peptide or (spacer)z-peptide is a dipeptide, the dipeptide being one of phenylalanine-arginine (Phe-Arg) or phenylalanine-lysine (Phe-Lys), the spacer is PEG, and the degradable moiety is an amide bond, the degradable moiety allowing cleavage the drug moiety in the presence of a protease (patent claim 13), wherein the spacer comprises a member selected from the group consisting of polyethylene glycol (PEG), PEG 2, and para-aminobenzyloxy carbamate (PABC), and the fluorescent compound is associated with the non-mesoporous nanoparticle or within the core of the non-mesoporous nanoparticle (patent claim 14), wherein the protease is serine protease including trypsin, or cysteine protease including cathepsin B (patent claim 15), wherein the receptor tyrosine kinase (RTK) inhibitor is dasatinib or gefitinib (patent claim 16), wherein the targeting moieties include cyclic arginylglycylaspartic acid (cRGD) (patent claim 17), and a nanoparticle drug conjugate (NDC) comprising: a non-mesoporous nanoparticle; an enzyme sensitive linker moiety; and a drug moiety, wherein the NDC has a diameter less than 10 nm, wherein the non-mesoporous nanoparticle is coated with an organic polymer, and wherein the drug moiety and enzyme sensitive linker moiety form a cleavable linker-drug construct that is covalently linked to the non-mesoporous nanoparticle and that facilitates enzyme catalyzed drug release, and wherein: (i) the drug moiety includes a member selected from the group consisting of dasatinib, gefitinib, an analog of dasatinib, and an analog of gefitinib, (ii) the organic polymer comprises at least one bifunctionalized maleimide silyl-polyethylene glycol group attached to at least one enzyme cleavable linker-drug construct, (iii) the cleavable linker-drug construct is formed via a protease, the enzyme cleavable linker-drug construct being linked to the non-mesoporous nanoparticle via the enzyme sensitive linker moiety, and (iv) the average drug moiety to non-mesoporous nanoparticle ratio ranges from 1 to 20 (patent claim 18), wherein the enzyme sensitive linker moiety comprises one or more amino acids (patent claim 19), wherein the enzyme sensitive linker moiety comprises (Amino-(spacer)x)y-peptide or (spacer)z-peptide, wherein the spacer has from 2 to 50 atoms, wherein x is an integer from 1 to5, wherein y is an integer from 1 to 5, wherein z is an integer from 5 to 15, andwherein the enzyme sensitive linker moiety comprises a degradable moiety between the enzyme sensitive linker moiety and the drug moiety (patent claim 20) wherein the enzyme sensitive linker moiety comprises a spacer between a peptide and the drug moiety (patent claim 21), comprising a fluorescent compound (patent claim 22), further comprising a radiolabel (patent claim 23), wherein the enzyme sensitive linker moiety is capable of undergoing hydrolysis at a C-terminal end upon protease binding, thereby releasing the drug moiety from the non-mesoporous nanoparticle (patent claim 24), wherein the drug moiety comprises a receptor tyrosine kinase (RTK) inhibitor, further comprising from 1 to 20 targeting moieties, wherein the targeting moieties bind to receptors on tumor cells (patent claim 26), wherein the NDC is a theranostic Ipatent claim 27), wherein the fluorescent compound is Cy5.5 (patent claim 28), wherein the drug moiety is attached to the radiolabel (patent claim 29), wherein the one or more amino acids include a peptide or polypeptide, and include 1 to 10 amino acids, the (Amino-(spacer)x)y-peptide or (spacer)z-peptide is a dipeptide, the dipeptide being one of phenylalanine-arginine (Phe-Arg) or phenylalanine-lysine (Phe-Lys), the spacer is PEG, and the degradable moiety is an amide bond, the degradable moiety allowing cleavage the drug moiety in the presence of a protease (patent claim 30), wherein the spacer comprises a member selected from the group consisting of polyethylene glycol (PEG), PEG2, and para-aminobenzyloxy carbamate (PABC), and the fluorescent compound is associated with the non-mesoporous nanoparticle or within the core of the non-mesoporous nanoparticle (patent claim 23), wherein the protease is serine protease including trypsin, or cysteine protease including cathepsin B (patent claim 24), wherein the receptor tyrosine kinase (RTK) inhibitor is dasatinib or gefitinib, including analogs thereof, or pharmaceutical or therapeutic equivalents thereof, modified to provide attachment to the enzyme sensitive linker moiety without perturbing underlying chemical structure of an active binding site of the drug moiety (patent claim 25), wherein the targeting moieties include cyclic arginylglycylaspartic acid (cRGD), anticipate the present claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL W DICKINSON whose telephone number is (571)270-3499. The examiner can normally be reached on M-F 9 AM to 7:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL W DICKINSON/Primary Examiner, Art Unit 1618
September 8, 2026
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