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 .
DETAILED ACTION
This office action is response to communication filed on 12/19/2025.
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on 12/19/2025.
Election/Restrictions
Applicant elected without traverse of Group II, claims 8-13 and phospholipids species (e.g. PC, PG, CH, PS, etc.) or combination thereof in liposome dosage form, in the reply filed 08/26/2025.
Claims 1-7 and 14-20 remain withdrawn being directed to non-elected inventions, there being no allowable generic or linking claim.
Claims 8-13 read on the liposome dosage form. It’s noted Applicant elects phospholipid genus in liposome dosage form without specifying phospholipid species, e.g. specific PC, PG, PS, etc. to be combined with Bryostatin-1 or analog thereof in liposome dosage form. PC, PG and PS are subgenus of phospholipids and each of PC, PG, PS subgenus/class comprise vast variety of species from different combinations of fatty acids. Applicant’s election is not considered as in compliance with the examiner’s requirement of species election mailed on 06/26/2025.
To expedite prosecution, the PC, PG, PS recited in instant claims 8-13 are considered as combination of any PC, PG, PS, or combination thereof under broadest reasonable interpretation BRI.
Status of Claims
Claims 1-20 are pending in instant application.
Claims 1-7 and 14-20 remain withdrawn.
Claims 8-13 are currently under examination in this office action.
Action Summary
Applicant's remarks filed 12/19/2025 have been fully considered. Any objection and rejection found in the previous Office Action and not repeated herein has been withdrawn in view of amendment and Applicant’s remarks .The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
As necessitated by amendment, claims 8-13 are newly rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement, and under 35 U.S.C. 112(b).
Maintained rejections:
Claim 12 rejected under 35 U.S.C. 112(b).
Rejections anticipated by Castor'486 (US 5,776486 B2) and Castor '155 (US 2018/0133155 A1) under 35 U.S.C. 102;
Claims 8-13 rejected under 35 U.S.C. 103 as being unpatentable over Castor '486, in view of Castor '155 and Alexander et al. ( US 2012/0309818 A1).
Rejections on the ground of non-statutory double patenting over US10493030B2 and 5,776486 B2 (Applicant filed Terminal Disclaimer over US10493030 B2 on 12/19/2025. However, the filed TD was not approved according to the record).
Priority
This application 17/911,070 filed on 09/12/2022 is a 371 of PCT/US2020/022397 filed on 03/12/2020.
Claim Interpretation
Claim 8 is amended to recite “ a dosage form for treating transplantation injury by reducing neutrophil trans-endothelial migration via activation of protein kinase C-delta (PKC-), comprising an effective amount of Bryostatin -1, Bryostatin -1 analog or a pharmaceutically acceptable salt thereof, wherein said dosage form is a liposomeal formulation comprising one or more phospholipid bilayers, each bilayer having a hydrophobic lipid region, and wherein Brvostatin-1 is incorporated within said hydrophobic lipid region of the phospholipid bilayer, wherein the liposomal formulation is a sterile, isotonically acceptable and pH-acceptable aqueous formulation configured for perfusion into a harvested transplantation organ prior to implantation in a human or animal”.
Instant claims are product claims. The recited limitation “ for treating transplantation injury...” “ reducing neutrophil trans-endothelial migration...”, “for perfusion into a harvested transplantation organ...” etc. are constructed as intended use/function of bryostatin-1 and analog thereof which do NOT necessarily contribute to the structural limitation of bryostatin-1 liposome dosage form. The biological/ pharmacological activity is the property of bryostatin-1 and analog thereof. In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. If the prior art structure is capable of performing the intended use/function, then it meets the limitation.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o).
Claim 8 is amended to recite “ a dosage form for treating transplantation injury by reducing neutrophil trans-endothelial migration via activation of protein kinase C-delta (PKC-), comprising an effective amount of Bryostatin -1, Bryostatin -1 analog or a pharmaceutically acceptable salt thereof, wherein said dosage form is a liposomal formulation comprising one or more phospholipid bilayers, each bilayer having a hydrophobic lipid region, and wherein Brvostatin-1 is incorporated within said hydrophobic lipid region of the phospholipid bilayer, wherein the liposomal formulation is a sterile, isotonically acceptable and pH-acceptable aqueous formulation configured for perfusion into a harvested transplantation organ prior to implantation in a human or animal”.
Instant specification does not disclose phospholipid bilayer having a hydrophobic lipid region and does not disclose Brvostatin-1 is incorporated within said hydrophobic lipid region of the phospholipid bilayer. Instant specification only discloses embodiments of sterile, isotonically acceptable and pH acceptable aqueous solution. Please note liposomal formulation is NOT aqueous formulation. As such, the specification fails to provide sufficient support for instantly claimed liposomal formulation comprising one or more phospholipid bilayers, each bilayer having a hydrophobic lipid region, and wherein Brvostatin-1 is incorporated within said hydrophobic lipid region of the phospholipid bilayer, wherein the liposomal formulation is a sterile, isotonically acceptable and pH-acceptable aqueous formulation.
Claim 12 is amended by adding limitation “wherein CH is cholesterol”. Instant specification does not disclose what the short acronym “CH” stands for. As such, the amended limitation “CH is cholesterol” lacks antecedent basis in instant specification.
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.
Claims 8-13 are rejected under 35 U.S.C. 112(a) 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. This is a written description rejection, rather than an enablement rejection under 35 U.S.C. 112, first paragraph. Applicant is directed to the MPEP 2163 and Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1st "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001 (newly applied as necessitated by amendment).
Independent claim 8 is amended to recite “ a dosage form for treating transplantation injury by reducing neutrophil trans-endothelial migration via activation of protein kinase C-delta (PKC-), comprising an effective amount of Bryostatin -1, Bryostatin -1 analog or a pharmaceutically acceptable salt thereof, wherein said dosage form is a liposomal formulation comprising one or more phospholipid bilayers, each bilayer having a hydrophobic lipid region, and wherein Brvostatin-1 is incorporated within said hydrophobic lipid region of the phospholipid bilayer, wherein the liposomal formulation is a sterile, isotonically acceptable and pH-acceptable aqueous formulation configured for perfusion into a harvested transplantation organ prior to implantation in a human or animal”.
MPEP 2163.02 states “ Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, the inventor was in possession of the invention, and that the invention, in that context, is whatever is now claimed”. The Applicant is required to provide adequate written description and evidence of possession of a liposomal formulation of Bryostatin -1 analog or a pharmaceutically acceptable salt thereof comprising one or more phospholipid bilayers, each bilayer having a hydrophobic lipid region, and wherein Brvostatin-1 is incorporated within said hydrophobic lipid region of the phospholipid bilayer, wherein the liposomal formulation is a sterile, isotonically acceptable and pH-acceptable aqueous formulation.
Instant specification does not disclose phospholipid bilayer having a hydrophobic lipid region and does not disclose Brvostatin-1 is incorporated within said hydrophobic lipid region of the phospholipid bilayer. Instant specification only discloses embodiments of sterile, isotonically acceptable and pH acceptable aqueous solution. Please note liposomal formulation is NOT aqueous formulation. As such, the specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed. Applicant is reminded that MPEP 2161 II makes clear that “The written description requirement is separate and distinct from the enablement requirement”.
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.
Claims 8-13 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.
Independent claim 8 is amended to recite a dosage form wherein the liposomal formulation is a sterile, isotonically acceptable and pH-acceptable aqueous formulation. Please note liposomal formulation is NOT aqueous formulation. As such, the contradictory limitation does not clearly set forth the metes and bounds of claim 8 for the patent protection desired. Claims 9-13 are rejected as depending from claim 8.
Claim 12 depends on claim 8 and recites “wherein the lipid composition of the liposome is selected from the group of the following lipid compositions: PC:CH in a 1:1 molar ratio ; PC:CH in a 2:1 molar ratio; PC:PG:CH in a 1.0:1.0:0.4 molar ratio; PC:PS:CH in a 1.0:1.0:0.4 molar ratio; DMPC:DMPG:CH in a 1.0:1.0:0.4 molar ratio;PC:DMPG:CH:DSPE-PEG2000 in a 1.0:1.0:0.35:0.05 molar ratio”.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 12 recites the broad recitation “PC:CH in a 2:1 molar ratio “ without specifying any PC, and also recites combination with narrower limitation of PC: PG : CH is 1.0:1.0: 0.4 and PC:PS:CH in a 1.0:1.0:0.4 molar ratio. Claim 12 further recites ratio of DMPC:DMPG:CH wherein DMPC is a specific PC and narrow statement of PC and DMPG is a. specific PG and narrow statement of PG. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. The lack of clarity renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 8-9 and 11-12 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Castor (US 5,776486 B, hereinafter “Castor '486”) (maintained).
Castor'486 discloses a method of preparing liposome dosage form of hydrophobic drug (e.g. bryostatin-1) comprising phospholipid, wherein said hydrophobic drug is in the lipid bilayer of the phospholipid liposome (See abstract, Col. 2, lines 15-20; Col. 4, lines 9-15; Col 6. lines 1-10, 25-30; claims 1-2, 8-11, 14-15, 22-25 and 28-29). Castor'486 teaches liposomes are microscopic vesicles having single or multiple bilayer for drug delivery that can enhance a drug's efficacy, reduce a drug's toxicity and prolong the drug’s therapeutic effect (See Col. 1, lines 33- 43). Castor'486 teaches the hydrophobic drug is incorporated in the lipid bilayer (See Col. 25, lines 18-40; claims 11 and 25).
Regarding the phospholipid of instant claim 9, Castor'486 teaches phospholipids selected from group consisting of phosphatidylcholine. phosphatidylethanolamine, phosphatidylserine (See Col. 4, lines 31-44; Col. 23, lines 10-17; claims 8-9 and 22-23).
Regarding cholesterol of instant claim 11, Castor'486 claim 10 teaches cholesterol is used together with phospholipid in 1:2 ratio (See Col. 28, lines 48-50; claims 10 and 24) (which also reads on PC:CH in a 2:1 ratio of instant claim 12).
Castor'486 is silent about liposome dosage form comprising bryostatin / bryostatin-1 analogs for treating transplantation injury or other intended use. However, the biological/ pharmacological activity is the property of bryostatin-1 and analog thereof. In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. Castor'486 collectively teaches liposomes of hydrophobic drug (e.g. bryostatin-1) comprising phospholipid and cholesterol. As such, Castor’155 anticipates instant claimed invention.
Claims 8-13 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Castor (US 2018/0133155 A1, hereinafter “Castor '155”, corresponding to US10493030B2) (maintained).
Castor'155 discloses a liposome dosage form comprising a bryostatin (e.g. bryostatin-1) wherein said bryostatin is in the hydrophobic lipid bilayer of the phospholipid nanosome (See abstract, [0049], claims 1-16).
Regarding claim 9, Castor’155 teaches one or more phospholipids selected from the group consisting of phosphatidycholine PC, phosphatidylglycerol PG, phosphatidylserine PS, dimyristoylphosphatidylcholine DMPC, dimyristoylphosphatidylglycerol DMPG, phosphatidylethanolamine PE and polyethylene glycol conjugated distearylphosphatidylethanolamine ( DSPE-PEG 2000 or DSPE-PEG3500)(See [0039], [0059]; Table 1). Please note PEG 2000 or DSPE-PEG3500 also read on the molecular weight limitation of PEG of instant claim 10 .
Regarding claim 11, Castor’155 teaches hydrophobic compositions further comprise
a-tocopherol (vitamin E) and cholesterol(See [0039]). Castor’155 teaches cholesterol in nanosomes transforms the bilayer into an ordered fluid phase over a wide temperature range, and therefore, improves the stability of nanosomes in plasma(See [0059]).
Regarding the ratio limitation of instant claim 12, Castor’155 discloses phospholipids combinations wherein PC: CH is 1:1 and 2:1, etc.(See [0059], Table 1).
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Regarding the amount limitation of claim 13, Castor’155 teaches in-vitro studies suggest that very low concentrations of Bryostatin-1 (1-10, or 10-100 nM) (See [0044]-[0046], [0048], [0050], [0056]). Castor’155 teaches toxicities will be further reduced by encapsulating the active ingredients in liposomes which have been clinically shown to significantly reduce the in vivo toxicity of therapeutic drugs(See [0048]).
Castor’155 is silent about liposome dosage form comprising bryostatin / bryostatin-1 analogs for treating transplantation injury or other intended use. However, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. The biological/ pharmacological activity is the property of bryostatin-1 and analog thereof. In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. As discussed above, the liposome taught by the reference is structurally same or very similar to the claimed composition, thus, the reference composition should be capable of performing the claimed intended use if applicant’s invention functions as claimed. As such, Castor’155 anticipates instant claimed invention.
Response to Arguments
Applicant argues Castor'486 and Castor '155 do not disclose or inherently teach: treatment of transplantation injury, perfusion of harvested organs prior to implantation, reduction of neutrophil trans-endothelial migration, or PKC-S-mediated endothelial stabilization.
RESPONSE: As explained in Claim Interpretation and reiterated in above 102 rejections, instant claims are product claims. The recited limitation “ for treating transplantation injury...” “ reducing neutrophil trans-endothelial migration...”, “for perfusion into a harvested transplantation organ...” etc. are constructed as intended use/function of bryostatin-1 and analog thereof which do NOT necessarily contribute to the structural limitation of bryostatin-1 liposome dosage form. The biological/ pharmacological activity is the property of bryostatin-1 and analog thereof. In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. If the prior art structure is capable of performing the intended use/function, then it meets the limitation.
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.
Claims 8-13 are rejected under 35 U.S.C. 103 as being unpatentable over Castor '486 (US 5,776486 B2), in view of and Castor '155 (US 2018/0133155 A1) and Alexander et al. ( US 2012/0309818 A1) (maintained).
The collective teachings of Castor '486 and Castor'155 are elaborated in preceding 102 rejection and applied as before. Both Castor '486 and Castor'155 teach a liposome comprising a bryostatin, phospholipids and cholesterol, wherein said Bryostatin is in the hydrophobic lipid bilayer of the liposome/ nanosomes.
Castor '486 is silent about polyethylene glycol conjugated distearylphosphatidylethanolamine and the amount of Bryostatin.
Castor'155 teaches phospholipids selected from the group consisting of phosphatidycholine PC, phosphatidylglycerol PG, phosphatidylserine PS, dimyristoylphosphatidylcholine DMPC, dimyristoylphosphatidylglycerol DMPG, phosphatidylethanolamine PE and polyethylene glycol conjugated distearylphosphatidylethanolamine ( DSPE-PEG 2000 or DSPE-PEG3500)(See [0039], [0059]; Table 1). Please note DSPE-PEG 2000 or DSPE-PEG3500 read on the molecular weight limitation of PEG of instant claim 10. Castor'155 teaches polyethylene glycol modification of the phospholipid wherein PEG coating produce 'stealth' liposomes which make them non-recognizable by phagocytes and hence resistant to their uptake and increase residence time and therapeutic index (See [0042], [0062]-[0063]).
Castor '486 and Castor'155 are silent about bryostatin for treating transplantation injury.
Alexander teaches a dosage form for treating transplantation injury comprising an effective amount of Bryostatin-1, Bryostatin-1 analog or a pharmaceutically acceptable salt thereof (See [0036]; [0049]-[0050], claims 4, 7-8, 14-20, 26-43). Alexander teaches Bryostatin-1, Bryostatin-1 analog or salt thereof is dispersed or dissolved in a polyalkylene glycol glyceride (e.g. polyethylene glycol) and in parenteral formulation which is isotonic acceptable and pH acceptable, aqueous solution or suspension for direct injection/administration (See [0036], claims 28 and 35-39). Alexander also teaches UW transplantation solution or other organ transplantation comprising Bryostatin-1 up to 10-7 M (See [0050]) (which reads on instant claim 13).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of instant invention to optimize the liposome dosage form comprising bryostatin and phospholipids taught by Castor '486, with the teachings of Castor ' 155 , further explore the liposome dosage form for treating transplantation injury as taught by Alexander, and arrive at instantly claimed invention with reasonable expectation of success. The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to further optimize combination of inactive ingredients and ratio thereof for desired pharmacokinetic and stability profile. The combined teachings of prior art, together with optimization based on general knowledge of liposome dosage form would provide a liposome dosage form comprising bryostatin, phospholipids including PEG modified PG (e.g. DSPE-PEG) and cholesterol at desirable ratio with increasing residence time and therapeutic index for treating transplantation injury.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the teachings of prior art, together with further optimization based on general knowledge of liposome dosage composition. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues Alexander teaches systemic immunosuppression and does not address endothelial conditioning, neutrophil TEM, PKC-6 activation, or transplantation organ perfusion. The present claims are directed to a mechanistically distinct therapeutic approach supported by experimental data demonstrating durable inhibition of neutrophil extravasation and improved transplant outcomes.
RESPONSE: As explained in Claim Interpretation and reiterated in above 103 rejection, instant claims are product claims, NOT method of treatment. The recited limitation “ for treating transplantation injury...”, “ reducing neutrophil trans-endothelial migration...”, “for perfusion into a harvested transplantation organ...” , etc. are constructed as intended use/function of bryostatin-1 and analog thereof which do NOT necessarily contribute to the structural limitation of bryostatin-1 liposome dosage form.
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 8-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 7, 11 of U.S. Patent No. US10493030 B2 (US20180133155A1 in preceding 102 rejection) . Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claims are directed a liposome comprising a bryoid, wherein the bryoid is in the hydrophobic lipid bilayer. Reference claim 4 recites Bryoid is selected from the group of Bryostatins consisting of Bryostatin 1-20.
Regarding phospholipids, reference claims 6 and 11 recite phospholipids selected from the group consisting of phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylserine (PS), dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG), phosphatidylethanolamine (PE) and polyethylene glycol conjugated distearylphosphatidylethanolamine, or combination thereof and ratio thereof (which read on instant claims 9 and 12). Reference claim 7 recites polyethylene glycol has a molecular weight of 2000 to 3500 Daltons (which reads on instant claim 10).
The scope of liposomes of reference claims comprising Bryostatin-1 in combination with another active ingredient is narrower than instant claims. Thus, reference claims anticipate instant claims.
The instant application shares at least one common inventor/applicant with the reference patent. Based on the continuing data on the record, instant application is not related to the reference patent, thus no 35 USC 121 shield exists.
Claims 8-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 8-11, 14-15, 22-25, 28-29 of U.S. Patent No. 5,776486 B2 in view of Castor '155, (US20180133155A1).
Reference claims are directed to method of making liposome for hydrophobic drugs (e.g. Bryostatin-1) comprising phospholipids. Reference claims 8 and 9 recite phospholipids selected from group consisting of phosphatidylcholine. phosphatidylethanolamine, phosphatidylserine that read on instant claim 9. Reference claim 10 recites cholesterol(which reads on instant claim 11). Reference claim 11 recites hydrophobic drug incorporated in its lipid bilayer.
Reference claims are silent about polyethylene glycol conjugated distearylphosphatidyl ethanolamine and the amount of Bryostatin. As elaborated in preceding 102 and 103 rejections and applied as before, Castor'155 teach a liposome comprising a bryostatin, phospholipids (including DSPE-PEG) and cholesterol in desired ratio.
It would have been obvious to a person of ordinary skill in the art to optimize the liposome dosage form comprising bryostatin and phospholipids taught by reference claims with the teachings of Castor ' 155, together with general knowledge of liposome dosage form and arrive at instantly claimed invention with reasonable expectation of success. The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to further optimize combination of inactive ingredients and ratio thereof for desired pharmacokinetic and stability profile. The combined teachings of reference claims and Castor'155 , together with optimization based on general knowledge of liposome dosage form would provide a liposome dosage form comprising bryostatin, phospholipids including PEG modified PG (e.g. DSPE-PEG) and cholesterol at desirable ratio with increasing residence time and therapeutic index.
The instant application shares at least one common inventor/applicant with the reference patent. Based on the continuing data on the record, instant application is not related to the reference patent, thus no 35 USC 121 shield exists.
Conclusion
No claims are allowed
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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/LIYUAN MOU/ Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628