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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/03/26 has been entered.
Receipt is acknowledged of Amendments, Remarks and a Terminal Disclaimer filed on 03/03/26. Claim 1 has been amended, claims 11 and 13 have been canceled and no new claims have been added. Accordingly, claims 1 and 3 remain pending and under examination on the merits.
NOTE: the amended portions of the claims are difficult to read. Applicant should consider an alternative type of font in the future.
Terminal Disclaimer
The terminal disclaimer filed on 03/03/26 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application No. 18/249,253 has been reviewed and is accepted. The terminal disclaimer has been recorded.
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 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (WO 2018024111) in view of Yeh et al (US 20130052270).
Sun ‘111 teaches the pharmaceutical use of a gold cluster and a substance containing the gold cluster for preventing and treating Alzheimer's disease and/or Parkinson's disease (See abstract).
Sun ‘111 teaches a gold cluster-containing material characterized by comprising a gold cluster and an externally coated ligand Y, wherein the gold cluster has a gold core diameter of less than 3 nm, preferably 0.5 to 2.6 nm (See claims 1-2).
The said ligand Y is selected from the group consisting of L(D)-cysteine and its derivatives, oligopeptides containing cysteine and their derivatives, and other compounds containing thiol. Specifically, L(D)-cysteine and its derivatives are selected from the group consisting of L(D)-cysteine, N-isobutyryl-L(D)-cysteine (L(D)-NIBC) or N-acetyl-L(D)-cysteine (L(D)-NAC), the oligopeptides containing cysteine and their derivatives are selected from the group consisting of L-arginine-L-cysteine (RC), L-cysteine-L-arginine (CR), L-cysteine-L-histidine dipeptide (CH), L-histidine-L-cysteine dipeptide (HC), L-glutathione (GSH), L-lysine-L-cysteine-L-proline tripeptide (KCP), L-proline-L-cysteine-L-arginine tripeptide (PCR), glycine-L-cysteine-L-arginine tripeptide (GCR), glycine-L-serine-L-cysteine-L-arginine tetrapeptide (GSCR), and glycine-L-cysteine-L-serine-L-arginine tetrapeptide (GCSR), and the other compounds containing thiol are selected from the group consisting of 1-[(2S)-2-methyl-3-thiol-1-oxopropyl]-L-proline (Cap), thioglycollic acid, mercaptoethanol, thiophenol, D-3-trolovol, N-(2-mercaptopropionyl)-glycine, and dodecyl mercaptan (See claims 3-9).
Sun ‘111 teaches a composition comprising the gold core nanoparticles and a ligand for treating CNS related conditions such as Alzheimer's disease and/or Parkinson's disease. However, Sun lacks a disclosure on administering the said composition to treat cerebral stroke in a subject. This would have been obvious in view of the teachings in the art such as Yeh et al.
Yeh et al teach the use of a gold nanocluster for ameliorating/treating oxidative stress and/or aging of a cultured cell or a subject having an oxidative stress and/or aging condition mediated by a vascular factor. The gold nanocluster has a particle size ranging from about 0.1 nm to 20 nm, and preferably is dihydrolipoic acid (DHLA) coated gold nanocluster (See abstract and [0010]).
Yeh et al teach that the said oxidative stress and/or aging condition of the subject is mediated by a vascular factor such as inflammation or a vascular disease. The vascular disease is any of atherosclerosis, coronary artery disease (CAD), myocardial infraction (Ml), ischemia, stroke, peripheral vascular disease, or pulmonary vascular disease (See [0011], [0024] and claim 12).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Yeh et al with that of Sun ‘111 to arrive at the instant invention with a reasonable expectation of success. It would have been obvious to do so because Sun discloses the compositions comprising a gold core and a ligand bound to the gold core for effective treatment of CNS related conditions such as Alzheimer's disease and/or Parkinson's disease. Yeh et al teach that gold nanoparticles were effective in treating cerebral ischemia-reperfusion injury. Sun discloses that gold nanoparticles have unique optical and electrical properties, good biocompatibility, easy surface modification and the ability to penetrate the blood-brain barrier at low concentrations. Yeh et al also teach that gold nanoclusters treat oxidative stress in a subject having an oxidative stress condition mediated by a vascular factor and thus effective in treating ischemia and stroke. One of ordinary skill in the art would have been motivated to treat cerebral stroke with the compositions of Sun because Yeh et al teach that gold nanoparticles are effective in treating stroke.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claims 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (WO 2018024111) in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742).
Sun ‘111’s teachings are delineated above and incorporated herein.
Sun ‘111 teaches a composition comprising the gold core nanoparticles and a ligand for treating CNS related conditions such as Alzheimer's disease and/or Parkinson's disease. However, Sun lacks a disclosure on administering the said composition to treat cerebral stroke in a subject. This would have been obvious in view of the teachings in the art such as Male et al and/or Yang et al.
Male et al teach a nanoparticle composition comprising: (a) a nanoparticle comprising: (i) a core comprising a metal, wherein the diameter of the core is in the range 1 nm to 5 nm; (ii) a corona comprising a plurality of ligands covalently linked to the core wherein said ligands comprise a carbohydrate; and
(b) at least one agent covalently attached to said core, which agent exhibits at least one therapeutic effect against a central nervous system (CNS) condition, said nanoparticle composition being for use in a method of treatment of said CNS condition including a tumor of the CNS; a neurodegenerative disease; stroke; a neurological disorder; a traumatic brain injury, etc, (See [0012] and claim 1).
Male et al disclose that the said core material is a metal selected from Au, Fe or Cu (See [0032]).
Yang et al teach a method of using metal nanoparticle or metallic particle to promote neurite outgrowth and treat and/or prevent neurological disorders. Particularly, the said method uses gold nanoparticles or gold particles to promote neurite outgrowth and treat and/or prevent neurological disorders (See abstract).
Yang et al teach that the size of said metallic nanoparticles can be between about 1 nm and about 100 nm, preferably about 1 nm to about 5 nm (See [0041]).
The said methods can be used to treat injury to the nervous system caused by physical, mechanical, or chemical trauma. Thus, the methods can be used in the treatment of peripheral nerve damage caused by physical injury, ischemia, as well as damage to the central nervous system due to, for example, stroke or intracranial hemorrhage (such as cerebral hemorrhage) (See [0054]-[0055] and claim 20).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Male et al and/or Yang et al with that of Sun ‘111 to arrive at the instant invention with a reasonable expectation of success. It would have been obvious to do so because Sun discloses the compositions comprising a gold core and a ligand bound to the gold core for effective treatment of CNS related conditions such as Alzheimer's disease and/or Parkinson's disease. Sun discloses that gold nanoparticles have unique optical and electrical properties, good biocompatibility, easy surface modification and the ability to penetrate the blood-brain barrier at low concentrations. Male et al also teach that gold nanoclusters are effective in treating CNS related conditions including stroke. Yang et al also teach that administering gold nanoparticles for treating various conditions including stroke, such as cerebral hemorrhage has been effective. One of ordinary skill in the art would have been motivated to treat cerebral stroke with the compositions of Sun because Male et al and/or Yang et al teach that gold nanoparticles are effective in treating stroke.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
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 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,729,718 in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application would have been obvious over the claims of U.S. Patent No. 10,729,718 in view of Male et al and/or Yang et al.
Specifically, the instant claims are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core.
The reference claims are directed to the composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core.
The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to the composition itself. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the composition of the reference claims for the method of instant claims for treating cerebral stroke with a reasonable expectation of success.
Claims 1 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,969,477 in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating glaucoma. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
Claims 1 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,413,355 in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of protecting against optic nerve damage. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
Claims 1 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,058,717 in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating Alzheimer's disease. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
Claims 1 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,000,543 in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating Parkinson’s disease. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
Claims 1 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-20 of U.S. Patent No. 12,310,985 in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating diabetes. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
Claims 1 and 3 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6-10 of copending Application No. 17/758,308 (US 20230037702) (reference application) in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating liver cirrhosis. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 3 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-10 of copending Application No. 18/546,269 (US 20240131182 and 20210226323) (reference application) in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating depression. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 3 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 9-11 of copending Application No. 18/725,231 (US 20250064970) (reference application) in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, instant claims are drawn to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The reference claims are directed to a similar composition and a method of treatment by administration of the said composition. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating multiple sclerosis, Alzheimer’s disease, liver cirrhosis, type 2 diabetes, Parkinson’s disease and glaucoma. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 3 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4-11 of copending Application No. 17/995,581 (US 20230158065) (reference application) (Allowed not yet issued) in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al .
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating adverse effects caused by an atypical antipsychotic. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 3 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of copending Application No. 17/222,229 (US 20210220394) (reference application) in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating Parkinson’s disease. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 3 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of copending Application No. 17/222,310 (US 20210220395) (reference application) in view of Male et al (EP 2956119) and/or Yang et al. Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating Alzheimer’s disease. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 3 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7-9 of copending Application No. 17/755,672 (US 20220401573) (reference application) in view of Male et al (EP 2956119) and/or Yang et al (US 20160015742). Although the claims at issue are not identical, they are not patentably distinct from each other because examined claims are obvious over the reference claims in view of Male et al and/or Yang et al.
Specifically, both the instant invention and reference Application are directed to a method of treatment by administration of a pharmaceutical composition comprising a ligand bound gold cluster comprising a gold core and ligand bound to the gold core. The difference is that instant claims are drawn to a method of treating cerebral stroke, while reference claims are drawn to a method of treating Multiple sclerosis. However, the prior art, including Male et al and/or Yang et al teach that gold nanoparticles can be used in a method of treating CNS related conditions including stroke. Thus, it would have been obvious to one of ordinary skill in the art to have administered the same compositions for treating liver cirrhosis and/or cerebral stroke with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Sun (US 20190175753).
Sun ‘753 teaches the use of a gold cluster or a gold cluster-containing substance in the preparation of a drug for preventing and/or treating glaucoma (See abstract).
Sun ‘753 teaches a pharmaceutical composition for preventing and/or treating glaucoma, said pharmaceutical composition comprising a substance containing gold clusters, wherein said substance comprises: gold clusters (AuCs); a ligand Y coating the AuCs externally; and a pharmaceutically acceptable excipient (See at least claim 1), and wherein the gold core diameter of the AuCs is smaller than 3 nm, and preferably from 0.5-2.6 nm (See claims 4-5).
The said pharmaceutical composition comprises the ligand Y selected from the group consisting of L(D)-cysteine and its derivatives, oligopeptides containing cysteine and their derivatives, and other compounds containing thiol. Specifically, L(D)-cysteine and its derivatives are selected from the group consisting of L(D)-cysteine, N-isobutyryl-L(D)-cysteine (L(D)-NIBC) or N-acetyl-L(D)-cysteine (L(D)-NAC), the oligopeptides containing cysteine and their derivatives are selected from the group consisting of L-arginine-L-cysteine (RC), L-cysteine-L-arginine (CR), L-cysteine-L-histidine dipeptide (CH), L-histidine-L-cysteine dipeptide (HC), L-glutathione (GSH), L-lysine-L-cysteine-L-proline tripeptide (KCP), L-proline-L-cysteine-L-arginine tripeptide (PCR), glycine-L-cysteine-L-arginine tripeptide (GCR), glycine-L-serine-L-cysteine-L-arginine tetrapeptide (GSCR), and glycine-L-cysteine-L-serine-L-arginine tetrapeptide (GCSR), and the other compounds containing thiol are selected from the group consisting of 1-[(2S)-2-methyl-3-thiol-1-oxopropyl]-L-proline (Cap), thioglycollic acid, mercaptoethanol, thiophenol, D-3-trolovol, N-(2-mercaptopropionyl)-glycine, and dodecyl mercaptan (See claims 6-9).
Sun (EP 3449945).
Sun ‘945 teaches the pharmaceutical use of a gold cluster and a substance containing the gold cluster for preventing and treating Alzheimer's disease and/or Parkinson's disease (See abstract).
Sun ‘945 teaches a gold cluster-containing material characterized by comprising a gold cluster and an externally coated ligand Y, wherein the gold cluster has a gold core diameter of less than 3 nm, preferably 0.5 to 2.6 nm (See claims 1-2).
The said ligand Y is selected from the group consisting of L(D)-cysteine and its derivatives, oligopeptides containing cysteine and their derivatives, and other compounds containing thiol. Specifically, L(D)-cysteine and its derivatives are selected from the group consisting of L(D)-cysteine, N-isobutyryl-L(D)-cysteine (L(D)-NIBC) or N-acetyl-L(D)-cysteine (L(D)-NAC), the oligopeptides containing cysteine and their derivatives are selected from the group consisting of L-arginine-L-cysteine (RC), L-cysteine-L-arginine (CR), L-cysteine-L-histidine dipeptide (CH), L-histidine-L-cysteine dipeptide (HC), L-glutathione (GSH), L-lysine-L-cysteine-L-proline tripeptide (KCP), L-proline-L-cysteine-L-arginine tripeptide (PCR), glycine-L-cysteine-L-arginine tripeptide (GCR), glycine-L-serine-L-cysteine-L-arginine tetrapeptide (GSCR), and glycine-L-cysteine-L-serine-L-arginine tetrapeptide (GCSR), and the other compounds containing thiol are selected from the group consisting of 1-[(2S)-2-methyl-3-thiol-1-oxopropyl]-L-proline (Cap), thioglycollic acid, mercaptoethanol, thiophenol, D-3-trolovol, N-(2-mercaptopropionyl)-glycine, and dodecyl mercaptan (See claims 3-9).
Response to Arguments
Applicant's arguments filed 03/03/26 have been fully considered but they are not persuasive.
Applicant’s amendments to the claims have necessitated modified grounds of rejections. Applicant’s arguments so far as they pertain to the maintained references and rejections are discussed below.
Applicant’s main argument regarding the teachings of the references is that they do not teach a composition for treating cerebral stroke in a subject.
Regarding the rejection of claims as being obvious over Sun ‘111 in view of Yeh et al, Applicant argues that 1- Yeh et al discloses dihydrolipoic acid (DHLA) coated gold nanocluster as the only ligand and do not teach the claimed ligands, and 2- Yeh et al discloses DHLA coated gold nanoclusters for the treatment of various vascular and inflammatory diseases and 3- Yeh provides absolutely no data showing the effectiveness of their DHLA coated gold nanoclusters for treating any disease (Applicant points to [0011] of Yeh et al) (See Remarks, page 5).
The above arguments are not found convincing. Firstly, it is noted that the examined claims do not exclude DHLA coated gold nanoclusters. Secondly, Yeh et al was relied upon for its disclosure of treating various diseases such as stroke by administration of a coated gold nanocluster, not the ligand itself. This was taught by Sun, the primary reference. Thirdly, Yeh et al specifically disclose a method for treating an oxidative stress and/or aging condition of a subject. The said vascular disease is any of atherosclerosis, coronary artery disease (CAD), myocardial infraction (Ml), ischemia, stroke, peripheral vascular disease, or pulmonary vascular disease. The subject is a human or an animal, preferably a mammal” (See [0011] and claims 10-12). Additionally, it is noted that a reference is considered for all that it teaches and not the preferred embodiments or examples. In this regard, the courts have held that “It is well-established that consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches, when viewed in light of the submitted knowledge in the art, to a person of ordinary skill in the art”. In re Boe, 355, F.2d 961, 148 USPQ 510, 510 (CCPA 1966).
The reference is not required to show data, but a teaching. Yeh clearly discloses that the gold nanoclusters can be administered to treat the said diseases. Thus, Yeh fully meets the requirement of treating stroke.
Regarding the list of disease cited by Yeh et al, Applicant argues that “Now the simple question should be asked is: when facing a list of atherosclerosis, coronary artery disease (CAD), myocardial infraction (MI), ischemia, stroke, peripheral vascular disease, or pulmonary vascular disease, how should one skilled in the art get started? Try each of them to see whether Yeh's DHLA coated gold nanocluster can be used for treatment? Applicant would be grateful if the examiner could provide any guidance of how to translate Yeh's such a disclosure into practice and obtain any reasonably expected success. In the OA, the examiner seems certain to select the stroke in order to combine with Sun, what scientific or practical basis for making such a selection?” (See Remarks, page 5).
The above argument is not convincing and cannot remove the reference from the rejection. As stated in the rejection and reproduced by the Applicant (Yeh [0011]), Yeh teaches a method for treating an oxidative stress condition, including vascular diseases such as atherosclerosis, coronary artery disease (CAD), myocardial infraction (Ml), ischemia, stroke, peripheral vascular disease, or pulmonary vascular disease. Thus, Yeh clearly teach that any of the said conditions are effectively treated by the disclosed coated gold nanoclusters. There is no need for the person of skilled art to “get started” with a condition, as it is clearly disclosed that ANY of the listed conditions will be effectively treated. As taught by Male et al, as well and the many copending Applications and Patents, it is clear that the same compositions are effective in treating multiple diseases and conditions.
Additionally, the examiner directs applicant’s attention to MPEP 2121: prior art is presumed operable/enabling. Once such a reference is found, the burden is on applicant to provide facts rebutting the presumption of operability. In re Sasse, 629 f.2d 675, 207 USPQ 107 (CCPA 1980). Thus, If Applicants have evidence that any of the listed conditions are not effectively treated by the compositions of Yeh, they should place the evidence on the record.
Furthermore, the examiner respectfully argues that absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. See MPEP 2145.
Next argument is regarding the particle size. Applicant argues that Yeh teach a particle size range of from 0.1 to 20 nm, but Liu teach that 5 nm particles were not effective in treating stroke while 20 nm were preferred (See Remarks, page 7).
This argument is also not found convincing. The particle size range for the claimed ligand-bound gold nanoclusters is taught by Sun, the primary reference. Yeh is relied upon for its disclosure on treating conditions including stroke with gold nanoparticles. Liu et al’s reference is not a prior art here.
Additionally, Applicant appears to assign a very narrow skill set to one skilled in the art. The Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). As indicated in the rejection supra, it would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Yeh et al with Sun to arrive at the instant invention. Again, the particle size range and the gold nanoclusters are taught by Sun.
Regarding the rejection of claims as being obvious over Sun ‘111 in view of Male et al, Applicant argues that 1- Male fails to teach the specific ligands as claimed and 2- Male discloses nanoparticles that are solely used as delivering vehicle (See Remarks, page 8-9).
These arguments have been fully considered but found unpersuasive. Male et al is a secondary reference teaching what is missing from the primary reference, Sun ‘111. That is, it was not relied upon for teaching the ligands of claim 1, but a method of treating cerebral stroke. Male et al teach that “said nanoparticle composition being for use in a method of treatment of said CNS condition in a mammalian subject, wherein the agent is delivered to astrocytes of the CNS by association with said nanoparticle, and wherein said CNS condition is selected from the group consisting of: a tumour of the CNS; a neurodegenerative disease; stroke; a neurological disorder; an infection of the CNS; an immune disorder of the CNS; a psychiatric disorder; a genetic abnormality affecting the CNS; and a traumatic brain injury”.
In this regard the courts have held that “the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Additionally, the examined claims use the open-ended transitional phrase of “comprising” which allows for unrecited components. That is, there is no exclusion of a therapeutic compound from claimed method.
Furthermore, the additional reference Yang et al teaches that gold nanoparticles can be effectively administered to treat conditions including stroke.
Applicant’s arguments regarding the rejection claims under obviousness type double patenting are similarly unpersuasive.
Regarding the rejection of claimed method of treating cerebral stroke over a reference patent or Application in view of Male et al, Applicant argues that neither the reference claims are directed to treating cerebral stroke nor do Male et al teach the claimed method. Applicant askes “how could the treatment of ….. and stroke be combined? Applicant points to their previous arguments regarding Male et al.
These arguments are also not found persuasive because, as stated above, Male et al teach that “said nanoparticle composition being for use in a method of treatment of said CNS condition in a mammalian subject, wherein the agent is delivered to astrocytes of the CNS by association with said nanoparticle, and wherein said CNS condition is selected from the group consisting of: a tumour of the CNS; a neurodegenerative disease; stroke; a neurological disorder; an infection of the CNS; an immune disorder of the CNS; a psychiatric disorder; a genetic abnormality affecting the CNS; and a traumatic brain injury”.
As shown by the references of record and many co-pending patents and Applications, the gold nanoparticles have been recognized as effective in treating many conditions and diseases and thus, it would have been obvious to one of ordinary skill in the art to have substituted one condition for another by administration of the same composition with a reasonable expectation of success.
Regarding the question of how can treatments of … and stroke be combined, it is noted that the treatments are not combined, rather the references show that because of the different teachings in the art, one of ordinary skill in the art would be motivated to administer Sun’s gold-ligand nanoparticles to a subject for treating various conditions as taught by the references, such as Male et al, Yang et al, Yeh et al and as evidenced by the many co-pending applications involved in the double patenting rejections.
The rejections are proper and minatianed.
Claims 1 and 3 are rejected.
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 Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached M-F, 7-5 EST.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616
Prosecution Insights