*DETAILED ACTION*
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
This application is a CON of 17/184,152 filed on 02/24/2021 (PAT 11,660,349), which is a is a CON of 16/182,261 filed on 11/06/2018 (PAT 10,933,144), which is a CON of 13/797,531 filed on 03/12/2013 (PAT 10,159,743), which claims benefit in provisional application 61/611,975 filed on 03/16/2012.
Claims Status
Claims 1-18 were canceled. Claims 19-36 are pending and examined.
Information Disclosure Statement
One of the IDS (3 pages) was not considered because it is not proper IDS according to 37 CFR 1.97 and 1.98.
Claim Objections
Claim 31 is objected to because it ends with two periods.
Claim Rejections – 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 19 and 21-34 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Zhang (US 2011/0262490 A1, Published October 27, 2011 – of record in IDS dated 01/09/2025).
The claims encompass a polymer conjugate, a composition comprising the polymer conjugate, and a method of using the composition.
Zhang teaches polymer-agent conjugates and particles for treatment of cancer (Abstract). The agent is an anti-cancer agent that is an anti-angiogenic agent (paragraphs 0016, 0168, 0363). Paragraphs 0028 and 0029 show a chemical structure of the conjugate where a drug is covalently bonded to the terminal of a polyglycolate. One embodiment comprises a particle comprising a first polymer and second polymer having a hydrophilic portion and a hydrophobic portion, and a therapeutic agent attached to the first polymer or the second polymer (paragraphs 0114-0117). In some embodiments the second polymer is a diblock copolymer comprising a hydrophobic polymer and a hydrophilic polymer (paragraph 0139). The hydrophobic portion is PLA, PGA, or PLGA (paragraph 0140) and the hydrophilic portion is PEG (paragraph 0141). In some embodiments, the hydrophilic portion has a terminal hydroxyl group (paragraph 0142). In some embodiments, the hydrophilic polymer is attached to the hydrophobic polymer by a covalent bond, or through an amide, ester, ether, amino, carbamate or carbonate linkage (paragraph 0144). In some embodiment, the agent is covalently bound to a PLGA polymer (paragraph 0 148).
Regarding claim 19, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the claimed invention to have formed a polymer-drug conjugate wherein the polymer is a diblock copolymer of a hydrophilic polymer covalently bonded to a hydrophobic polymer and the drug is an anti-angiogenic agent covalently conjugated to the end of the hydrophobic block, with a reasonable expectation of success because Zhang teaches a polymer-drug conjugate wherein the polymer is a block copolymer comprising a hydrophilic polymer covalently bonded to a hydrophobic polymer and where the drug is an anti-angiogenic agent covalently bonded to the end of the hydrophobic block. It would have been obvious have selected PEG as the hydrophilic polymer and PLA, PGA, or PLGA as the hydrophobic polymer because Zhang teaches that PEG is a suitable hydrophilic polymer and PLA, PGA, and PLGA are suitable hydrophobic polymers.
The limitation A is met because Zhang’s conjugate comprises an anti-angiogenesis agent and teaches that the conjugate may be used for ophthalmic applications (paragraph 1980, 1997, 2004).
The limitation Z is met because Zhang’s conjugate comprises PEG.
The limitation Y is met because Zhang’s conjugate has a PEG-PLGA (or PEG-PLA or PEG-PGA) where one of the repeating units either form PEG or the PLGA where the two polymers connect reads on a multivalent branch point that is organic. For example -CH2CH2O- that is immediately bonded to PLGA meets the limitation of Y.
The limitation X is met because Zhang’s block copolymer contains one of PLGA, PGA, or PLA.
The limitation where both of m and n are 1 is met because Zhang’s conjugate contains one PEG and one PLGA bonded to the drug. For example, PEG-PLGA-drug.
Regarding claim 21, Zhang teaches embodiments where the hydrophobic polymer of the diblock copolymer is PLA.
Regarding claims 22-25, 27-29, and 31-33, it would have been obvious to have selected the anti-cancer agent from an anti-VEGF compounds selected from bevacizumab, sunitinib, and sorafenib; or a tyrosine kinase inhibitor comprising terreic acid, with a reasonable expectation of success because Zhang teaches that anti-cancer agents may be delivered via the polymer-drug conjugate (paragraphs 1640-1643), where exemplary anti-cancer agents include Bruton's tyrosine kinase inhibitors comprising terreic acid (paragraph 1664), and VEGF pathway inhibitors comprising bevacizumab, sunitinib, and sorafinib (paragraph 1710).
The limitations that require an anti-VEGF compound are met by VEGF pathway inhibitors.
Limitations that require a receptor tyrosine kinase inhibitors are met because sunitinib is a receptor tyrosine kinase inhibitor, as evidenced by the instant specification.
Limitations that require a tyrosine kinase inhibitor are met by Burton’s tyrosine kinase inhibitors and sorafenib, as evidenced by instant specification.
Regarding claim 26, Zhang teaches PGA.
Regarding claim 30, Zhang teaches PLGA.
Regarding claim 34, it would have been obvious to have formulated the polymer-drug conjugate into nanoparticles, and suspended the nanoparticles into a pharmaceutically acceptable carrier, with a reasonable expectation of success because Zhang teaches the polymer-drug conjugates may be formulated into particles, and suspended in a pharmaceutically acceptable carrier (paragraphs 1009-1011). Pharmaceutically acceptable carrier is defined in paragraph 1598. The term "nanoparticle" refers to a material structure whose size in any dimension ( e.g., x, y, and z Cartesian dimensions) is less than about 1 micrometer (micron), e.g., less than about 500 nm or less than about 200 nm or less than about 100 nm, and greater than about 5 nm. A nanoparticle can have a variety of geometrical shapes, e.g., spherical, ellipsoidal, etc. (paragraph 1596). The claimed microparticles are obvious over Zhang’s nanoparticles because their particle size ranges overlap. According to instant specification, “microparticle” refers to a particle having a diameter from about 1 micron to about 100 microns. Zhang defines a “nanoparticle” as a material whose size in any dimension is less than about 1 micron. About 1 micron end of the range overlaps with less than about 1 micron.
Claims 35 and 36 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Zhang as applied to claims 19 and 21-34 above, and further in view of Robinson (WO 2010/009034 A3 Published January 21, 2010).
The teachings of Zhang are relied upon as summarized above. Zhang does not teach the limitations of claims 35 and 36.
The teachings of Robinson are related to compositions and methods for treating dry age related macular degeneration (dry AMD) by administration to an intraocular location of an anti-neovascular agent (such as bevacizumab) in either a liquid or solid polymeric vehicle (or both), such as a biodegradable hyaluronic acid or PLGA (or PLA) (Abstract). Bevacizumab is an anti-VEGF agent (page 10 lines 25-26). Glaucoma can also be treated with the drug delivery systems and methods disclosed in Robinson (page 27 lines 20-25). Choroidal neovascularization may also be treated (page 28 lines 18-23). The drug delivery systems can be injected to an intraocular location by syringe (page 27 lines 30-31).
The teachings of Robinson and Zhang are related to composition comprising an anti-VEGF agent where the compositions are intended for treating an eye disorder and the composition is administered by injection, and it would have been obvious to have combined their teachings because they are in the same field of endeavor.
It would have been prima facie obvious to a person of ordinary skill in the art at the time of the claimed invention to have treated glaucoma or choroidal neovascularization by administering the anti-VEGF agent bevacizumab via intraocular injection, with a reasonable expectation of success because Robinson teaches a method of treating glaucoma or choroidal neovascularization by administering the anti-VEGF agent bevacizumab via intraocular injection. It would have been obvious to have selected Zhang’s pharmaceutical composition comprising nanoparticles having particle size of less than about 1 micron wherein the nanoparticles comprise the anti-VEGF agent bevacizumab conjugated to the PLGA terminal of the PEG-PLGA block copolymer, and wherein the nanoparticles are suspended in a pharmaceutically acceptable carrier, with a reasonable expectation of success because Zhang teaches a pharmaceutical composition comprising nanoparticles having particle size of less than about 1 micron wherein the nanoparticles comprise the anti-VEGF agent bevacizumab conjugated to the PLGA terminal of the PEG-PLGA block copolymer wherein the particles are suspended in a pharmaceutically acceptable carrier. One of skill would have had a reasonable expectation of success because Zhang teaches that compositions are suitable for ophthalmic use and may be administered by injection. The selection of a known material based on its suitability for its intended purpose supports obviousness and combining prior art elements according to known methods to obtain predictable results supports obviousness.
Double Patenting Rejections
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 19-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-54 of U.S. Patent No. 9,950,072 B2 in view of Zhang.
Patented claims encompass polymer-drug conjugates. Patented claims do not teach PLA, PGA, or PLGA as the hydrophobic polymer segment in the conjugate.
The teachings of Zhang are relied upon as summarized above.
Patented claims and Zhang are related to polymer-drug conjugates and it would have been obvious to have combined them because they are in the same field of endeavor.
Instant claim 19 is obvious over patented claims 1-6, 10, and 11 when in patented claim 1: A is a HIF-1 inhibitor, X is a hydrophobic polymer segment that is a polyester, Y is a banching point selected from compounds in patented claims 10 and 11, Z is a hydrophilic polymer segment PEG, o is 1, p is 0, q is 0, m is an integer between 1 and 20, n is an integer between 1 and 20.
It would have been prima facie obvious to a person of ordinary skill in the art at the time of the claimed invention to have selected PLA, PGA, and PLGA as the hydrophobic polyesters in patented claims, with a reasonable expectation of success because it was known from Zhang that diblock copolymers having PEG as the hydrophilic segment and one of PLA, PGA, and PLGA as the hydrophobic segment is suitable for conjugation with anti-angiogenic drugs. The selection of a known materials based on its suitability for its intended purpose supports obviousness.
Instant claim 20 is obvious over patented claims 10 and 11.
Instant claim 21 is obvious because PLA would have been an obvious hydrophobic polyester in view Zhang.
Regarding claims 22-25, 27-29, and 31-33, it would have been obvious to have modified patented polymer-drug conjugate by replacing the HIF-1 with an anti-VEGF compounds selected from bevacizumab, sunitinib, and sorafenib; or a tyrosine kinase inhibitor comprising terreic acid, with a reasonable expectation of success because it was known from Zhang that anti-cancer agents including anthracyclines such as doxorubicin (paragraph 1650); Bruton's tyrosine kinase inhibitors comprising terreic acid (paragraph 1664), and VEGF pathway inhibitors comprising bevacizumab, sunitinib, and sorafinib (paragraph 1710) may be formulated in nanoparticles as polymer-drug conjugates where the polymer is a diblock copolymer of PEG (hydrophilic segment) and one of PLA, PGA, or PLGA (hydrophobic segment) where the drug is covalently bonded to the hydrophobic segment terminal. The anthracyclines (HIF-1 inhibitor), Bruton's tyrosine kinase inhibitors, and VEGF inhibitors are equally suitable for conjugation to PEG-PLGA and it would have been obvious to modify patented conjugate by replacing the HIF-1 inhibitors with Bruton's tyrosine kinase inhibitors and VEGF inhibitors as taught by Zhang.
The limitations that require an anti-VEGF compound are met by VEGF pathway inhibitors.
Limitations that require a receptor tyrosine kinase inhibitors are met because sunitinib is a receptor tyrosine kinase inhibitor, as evidenced by the instant specification.
Limitations that require a tyrosine kinase inhibitor are met by Burton’s tyrosine kinase inhibitors and sorafenib, as evidenced by instant specification.
Instant claim 26 is obvious because Zhang teaches PGA.
Instant claim 30 is obvious because Zhang teaches PLGA.
Instant claim 34 is obvious over patented claim 39.
Instant claim 35 is obvious over patented claims 47-51.
Claim 36 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-54 of U.S. Patent No. 9,950,072 B2 in view of Zhang, as applied to claims 19-35, and further in view of Robinson (WO 2010/009034 A3 Published January 21, 2010).
The teachings of patented claims and Zhang are relied upon as summarized above. They do not teach limitations of claim 36.
The teachings of Robinson are relied upon as summarized above.
It would have been obvious to have administered patented composition as modified by Zhang in a method of treating an ocular disorder such as choroidal neovascularization by administering the composition by intraocular injection, with a reasonable expectation of success because it was known from Robinson that intraocular injection is a suitable method of administering an active agent in a method of treating choroidal neovascularization. Combining prior art elements according to known methods to obtain predictable results supports obviousness and the selection of a known method based on its suitability for its intended purpose supports obviousness.
Claims 19-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of U.S. Patent No. 8,962,577 B2 (of record in IDS dated 01/09/2025) in view of Zhang.
Patented claims encompass polymer-drug conjugates. Patented claims do not teach PLA, PGA, or PLGA as the hydrophobic polymer segment in the conjugate.
The teachings of Zhang are relied upon as summarized above.
Patented claims and Zhang are related to polymer-drug conjugates and it would have been obvious to have combined their teachings because they are in the same field.
Instant claim 19 is obvious over patented claims 1-6 and 10, when in patented claim 1: A is a HIF-1 inhibitor, X is a hydrophobic polymer segment that is a polyester, Y is a branching point selected from compounds in patented claims 1 and 10, Z is a hydrophilic polymer segment PEG, o is 1, p is 0, q is 0, m is an integer between 1 and 20, n is an integer between 1 and 20.
It would have been prima facie obvious to a person of ordinary skill in the art at the time of the claimed invention to have selected PLA, PGA, and PLGA as the hydrophobic polyesters in patented claims, with a reasonable expectation of success because it was known from Zhang that diblock copolymers having PEG as the hydrophilic segment and one of PLA, PGA, and PLGA as the hydrophobic segment are suitable for conjugation with anti-angiogenic drugs. The selection of a known materials based on its suitability for its intended purpose supports obviousness.
Instant claim 20 is obvious over patented claims 1 and 10.
Instant claim 21 is obvious because PLA would have been an obvious hydrophobic polyester in view Zhang.
Regarding claims 22-25, 27-29, and 31-33, it would have been obvious to have modified patented polymer-drug conjugate by replacing the HIF-1 with an anti-VEGF compounds selected from bevacizumab, sunitinib, and sorafenib; or a tyrosine kinase inhibitor comprising terreic acid, with a reasonable expectation of success because it was known from Zhang that anti-cancer agents including anthracyclines such as doxorubicin (paragraph 1650); Bruton's tyrosine kinase inhibitors comprising terreic acid (paragraph 1664), and VEGF pathway inhibitors comprising bevacizumab, sunitinib, and sorafinib (paragraph 1710) may be formulated in nanoparticles as polymer-drug conjugates where the polymer is a diblock copolymer of PEG (hydrophilic segment) and one of PLA, PGA, or PLGA (hydrophobic segment) where the drug is covalently bonded to the hydrophobic segment terminal. The anthracyclines (HIF-1 inhibitor), Bruton's tyrosine kinase inhibitors, and VEGF inhibitors are equally suitable for conjugation to PEG-PLGA and it would have been obvious to modify patented conjugate by replacing the HIF-1 inhibitors with Bruton's tyrosine kinase inhibitors and VEGF inhibitors as taught by Zhang.
The limitations that require an anti-VEGF compound are met by VEGF pathway inhibitors.
Limitations that require a receptor tyrosine kinase inhibitors are met because sunitinib is a receptor tyrosine kinase inhibitor, as evidenced by the instant specification.
Limitations that require a tyrosine kinase inhibitor are met by Burton’s tyrosine kinase inhibitors and sorafenib, as evidenced by instant specification.
Instant claim 26 is obvious because Zhang teaches PGA.
Instant claim 30 is obvious because Zhang teaches PLGA.
Instant claim 34 is obvious over patented claims 29, 31, and 37.
Instant claim 35 is obvious over patented claims 37-42.
Claim 36 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of U.S. Patent No. 8,962,577 B2 in view of Zhang, as applied to claims 19-35, and further in view of Robinson (WO 2010/009034 A3 Published January 21, 2010).
The teachings of patented claims and Zhang are relied upon as summarized above. They do not teach limitations of claim 36.
The teachings of Robinson are relied upon as summarized above.
It would have been obvious to have administered patented composition as modified by Zhang in a method of treating an ocular disorder such as choroidal neovascularization by administering the composition by intraocular injection, with a reasonable expectation of success because it was known from Robinson that intraocular injection is a suitable method of administering an active agent in a method of treating choroidal neovascularization. Combining prior art elements according to known methods to obtain predictable results supports obviousness and the selection of a known method based on its suitability for its intended purpose supports obviousness.
Conclusion
No claims are allowed.
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/ALMA PIPIC/Primary Examiner, Art Unit 1617