DETAILED ACTION
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 Interpretation
Claim 8 recites major components of the nanoparticle. However, claim 8 is examined as intending to recite a group from which major component(s) of the nanoparticle can be selected.
Claim Objections
Claim 20 is objected to because of the following informalities:
Two periods and the phrase “degradable lipid nanoparticle” appears to be a typographical error.
Appropriate correction is required.
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.
Claim 8 is 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.
Claims reciting alternatives may be set forth as "a material selected from the group consisting of A, B, and C" or "wherein the material is A, B, or C". It is noted that amending claim 8 to recite “…selected from the group consisting of Au, Ag, SiO2, Si, glass, and resin” would obviate the rejection of claim 8.
Further, the term “major” in claim 8 is unclear because the percent amount of the component, relative to the whole particle, that warrants the designation of major component is not defined.
Please clarify.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sattiraju (Mol Cancer Ther, 2017 on IDS).
Sattiraju discloses 225Ac-labeled liposomes (liposome reads on biodegradable lipid nanoparticle of the instant application) containing a lipid conjugated at the polar head group with DOTA to bind Ac at the outside surface of the liposome (p. 2192 bottom left and Fig. 1 A - see lipid labeled DOTA and B – see liposome depiction on the far right). The method of manufacturing the radiolabeled liposomes comprises preparing the liposomes, mixing the liposomes with 225Ac and incubating the mixture for 50 min. (p. 2192 right column, Material and Methods section, paragraph heading: Radiolabeling of αvβ3-targeted IA-TLs with 225Ac).
The liposomes of Sattiraju are regarded as being biodegradable on an appropriate timescale.
Claim Rejections - 35 USC § 103
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.
Claims 1, 3 – 6 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Ishihara (WO 2021186233 A1) in view of Batra (US20140199242 on PTO-892).
Ishihara discloses a lipid particle manufacturing kit that combines compositions (p. 10 lines 10 – 20); a method of liposome particle manufacturing where compositions are prepared, mixed and stirred (p. 8 lines 19-33; “stirred” reads on “incubating” in the method of the instant application); compositions for delivering a substance to malignant tumor cells where a composition can contain a substance delivery carrier that is a lipid particle (claim 1), 70 – 100 nm in diameter (p. 5 line 27), reading on a biodegradable lipid nanoparticle of the instant application, with ingredients encapsulated inside the lipid particle, such as a therapeutic agent (p. 3 lines 21-22) or a radioisotope as a diagnostic agent (p. 17 lines 27-29) which reads on encapsulating a labeling substance of the instant application. The lipid particle contains a first lipid and second lipid (claims 1, 12, 15 and 20) where the relative amounts of the first and second lipid modify the cell permeability selectivity or endocytotic specificity of the lipid particle (p. 5 lines 17 to p. 6 line 12) which reads on the recited cell tropism of the instant application. The first and second lipids are the same cationic lipids recited and disclosed by the instant application (claim 5 of instant application and para. 39 of instant application). The two cationic lipids can account for 30% to 50% of the whole lipid ingredients of the particle (p. 5 lines 2 and 3). A third type of lipid that can be contained in the particles can be a lipid constituent of biological membranes (p. 6 lines 20-25), as is the case for the instant application (para. 36 of the instant application) and therefore the lipid particles of Ishihara are regarded as being biodegradable.
Ishihara does not teach radioactive material linked to the outside of the biodegradable lipid nanoparticle.
Batra discloses a bispecific antibody (para. 175) that binds an alpha emitter (para. 10), reading on radioactive material of the instant application, to the exterior polar surface of a liposome (para. 221) using a polymer in coupling to the liposome surface (para. 222) for detection and treatment of cancer (abstract). Liposomes, of diameter 80 – 400 nm (para 227), reads on lipid particle of Ishihara. Further, antibodies can be linked to preformed liposomes (para. 235). There is no disclosure regarding the amount of linker or linker-derivatized lipid content of the liposome.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the bispecific antibody of Batra into the lipid nanoparticle carrier compositions of Ishihara. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the prior art of Batra provides a strategy that could be used to enhance the selectivity in targeting cancer cells for therapeutic intervention. That is, Batra teaches a means of adding radioactive material to lipid particles and a means of targeting cancer cells with the lipid particles where both characteristics are achieved by linking an antibody to the surface of the lipid particles that binds a receptor on the surface of the cancer cell and that carries the radioactive material. The art of Ishihara delivers material, such as radioactive material, to a targeted cancer cell type selectively over other cell types, a process that could be bolstered by adapting the strategy of Batra.
The instant application recites specific cationic lipids at 10 – 50% of the total lipid content of the lipid nanoparticle which overlaps with the content of these lipids in the liposomes disclosed by the prior art of Ishihara where the lipid composition can be selected to modify cell permeability. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05.
Claims 1 - 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ishihara (WO 2021186233 A1) and Batra (US20140199242 on PTO-892) as applied to claims 1, 3 – 6 and 11 above, and further in view of Koga (Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2021) and Sporer (J. Nanotheranostics 2021 on PTO-892).
Ishihara and Batra are discussed above.
Ishihara and Batra do not teach a biodegradable lipid nanoparticle including a linker extending to an end of a portion of component lipid thereof, and a nanoparticle immobilized on the linker to immobilize the radioactive material.
Koga discloses gold nanoparticle coated liposomes (liposome reads on lipid particle of Ishihara) where the gold nanoparticle is attached/linked to the liposomes through the thiol functionality of glutathione on the surface of the liposomes (p. 2 left column, bottom and Fig. 1) and thermal release of a liposome encapsulated cancer drug triggered by laser light interaction with the gold particles (abstract).
Sporer discloses surface adsorption of the alpha-emitter astatine-211 to gold nanoparticles as being stable in vivo and potentially useful in radionuclide therapy (title).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the gold nanoparticles linked to the surface of liposomes disclosed by Koga and the surface adsorption of astatine-211 to gold nanoparticles disclosed by Sporer to modify the compositions, methods, and kits of Ishihara and Batra. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because therapeutic impact could be enhanced by triggered release of a cancer drug from liposomes near tumor cells as taught by Batra and by preserving the stability of the alpha emitter in vivo as taught by Sporer. A goal of the art taught by Ishihara is to deliver an encapsulated therapeutic agent to cancer cells. Thermally triggered release of encapsulated drug could be used to facilitate release of the encapsulated therapeutic agent delivered to cancer cells in the art disclosed by Ishihara, thereby enhancing therapeutic benefit. Sporer teaches an alpha emitter attached to a gold nanoparticle that is stable in vivo. The alpha emitter attached to the liposomes of Batra would require stability in vivo, such as the stability afforded by the art of Sporer, for maximized therapeutic benefit.
The method of the instant application is drawn to manufacturing the biodegradable lipid nanoparticle that exhibits cell tropism, encapsulates an active substance, and contains a particle linked to its outer surface that carries an active substance that can be an alpha emitter. The method of Ishihara is drawn to manufacturing lipid particles with specific lipid content as to modify cell permeation selectivity and that can encapsulate substances; the method comprising preparing compositions, mixing compositions, and incubating mixed compositions to obtain final lipid particle compositions. It would be obvious to one of ordinary skill in the art to implement the method of Ishihara to manufacture the compositions of the instant application because the two specific lipids used in the lipid particles of Ishihara to elicit cell tropism are the same two specific lipid recited in the instant application. Therefore, one of ordinary skill in the art would be motivated to use a method previously demonstrated to suffice in manufacture the particles, such as the method of Ishihara, as to avoid trial and error.
In the instant application, the diameter ratio of biodegradable lipid nanoparticle to nanoparticle is selected to be within the range of 1:1 to 100:1 as recited in claim 10. Ishihara discloses liposomes ranging in diameter between 70 nm and 100. The linker content on the biodegradable nanoparticle surface is selected to be within the range recited in claim 7 of the instant application (0.01 to 1%). Linking the nanoparticles to the biodegradable lipid nanoparticles as recited in the instant application (claim 2 of the instant application), where the diameters on the two particle types are of the same order of magnitude, would necessitate and be accommodated by an amount of linker, such as the glutathione of Koga, selected from the range recited in the instant application. That is, the lipid linker content of the liposomes of Koga is not defined and would be selected in portion to the size (liposome surface footprint) of the nanoparticle being linked to the liposome. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05.
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 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.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-13 of copending Application No. 19033705 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application describes a biodegradable lipid nanoparticle that exhibits cell tropism (claim 5), that encapsulates an active substance (claim 6), and that contains a particle linked (linker present at 0.1 – 1%, claim 7 of instant application) to its outer surface that carries an active substance that can be an alpha emitter (claims 1-11); a method for manufacturing the radiotherapy biodegradable lipid nanoparticle (claims 12-14); a combination composition comprising a biodegradable lipid nanoparticles having a linked nanoparticle on its surface that immobilizes the alpha emitter radioactive material (claims 15-17); a kit where the biodegradable lipid nanoparticles, which can contain a linked nanoparticle on its surface that can be gold (claim 8), is included independently from the alpha emitter radioactive material (claims 19-20) and US’705 recites a biodegradable particle-bound lipid nanoparticle that exhibits cell tropism (claim 4 of US’705), where the particle bound to the surface of the lipid nanoparticle can be gold (claim 7 of US’705) and can be linked (linker present at 0.1 -1%, claim 6 of US’705) to the surface of the lipid nanoparticle and where the lipid nanoparticle can encapsulate an active substance (claim 9 of US’705); a method for manufacturing the particle-bound lipid nanoparticle (claim 10 of US’705); a kit containing the biodegradable lipid particle, a particle bound or capable of binding to the outer surface of the lipid nanoparticle, and an active substance (claims 11 and 12 of US’705); a combination composition where a first composition is the particle-bound lipid nanoparticle and a second composition is the active substance (claim 13 of US’705). The active substance of US’705 reads on the alpha emitter of the instant application.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to implement the biodegradable particle-bound lipid nanoparticle and the method, kit, and combination compositions of US’705 to manufacture the biodegradable lipid nanoparticle of the instant application. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because US’705 has established the compositions and methods of manufacturing the compositions that match requirements of the instant application. That is, the structural features of the particle-bound lipid nanoparticle of US’705, where the alpha emitter is linked to the surface of the lipid nanoparticle using a second surface-linked nanoparticle, are shared structural features recited for the biodegradable lipid nanoparticle of the instant application.
The instant application recites nanoparticles bound to the surface of the biodegradable lipid nanoparticle without specifying absolute particle diameters but recites that the diameters of the biodegradable lipid nanoparticle and the second nanoparticle linked to the surface of the lipid nanoparticle can be equal (ratio of diameters is 1:1) or the diameter of the biodegradable lipid nanoparticle can be 100 times larger than the nanoparticle bound to its surface (ratio of diameters is 100:1). Claim 8 of reference application US’705 recites a diameter of the particle bound to the surface of the biodegradable lipid nanoparticle that is 1 nm to 10 um. The diameter of the nanoparticle linked to the surface of the lipid nanoparticle of the instant application could be selected as to be encompassed by the range of 1 nm to 10 um recited in US’705.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES DAVID BURGESS whose telephone number is (571)270-5640. The examiner can normally be reached Monday - Friday 8:30AM - 5:00PM.
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/JAMES D BURGESS/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
