FINAL 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 .
Status of the Claims
This action is in response to papers filed 06/23/2025 in which claim 9 was canceled; claim 12 was withdrawn; claims 1, 4-6, 8, and 10 were amended; and claim 13 was newly added. All the amendments have been thoroughly reviewed and entered.
Claims 1-8, 10, 11 and 13 are under examination.
Withdrawn Objections/Rejections
The Examiner has re-weighted all the evidence of record. Any rejections and/or objections not specifically addressed below is hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim Interpretation
Claims 1 and 13 are structured as a product-by-process. Thus, claims 1 and 13 will be interpreted and examined for art rejections purposes (102 and 103 rejections) as product-by-process type claim. MPEP 2113 [R-1] states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Thus, while the structure implied by the process steps should be consider when assessing patentability of product-by-process claims over the prior art; however, burden of proof is placed upon Applicant to show that the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). Also see MPEP § 2113.
Maintained-Modified Rejections
Modification Necessitated by Applicant’s Claim Amendments
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
Claim(s) 1-2, 7-8, 11, and 13 is/are rejected under 35 U.S.C. 102(a)(1) or 102(a)(2) as being anticipated by Tartis et al (WO 2019/200043 A1).
The product-by-process claim interpretation applies here.
Regarding claims 1, 11 and 13, Tartis teaches an ultrasound-assisted drug delivery carrier comprising microbubbles containing a ligand (phospholipid) conjugated to a drug via an ester bond, a phospholipid and a PEGylated phospholipid (Abstract; [028], [033], [049], [050]-[053], [085]-[087], [0155], [0199]; claim 43).
It is noted that the recitations of “the microbubbles or nanobubbles are formed by adding a sodium chloride aqueous solution and a 2H,3H-decafluoropentane to the ligand, phospholipid, and PEGylated phospholipid and apply first ultrasound thereto” as recited in claim 1 and “the first ultrasound is applied for 0.5 to 2 minutes” as recited in claim 13, are recitations of product-by-process.
As discussed above, the claimed structures of “an ultrasound-assisted drug delivery carrier comprising a ligand linked with a drug through an ester bond, a phospholipid, and a PEGylated phospholipid, wherein the drug delivery carrier is provided in a form of microbubbles or nanobubbles” have been taught by Tartis supra. The ultrasound-assisted drug delivery carrier of Tartis is structurally the same as the claimed ultrasound-assisted drug delivery carrier and thus, “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
It is noted that the recitation of “wherein the microbubbles or nanobubbles are collapsed by applying second ultrasound to the microbubbles or nanobubbles, wherein the hydrolysis of the ligand-drug ester bond is promoted due to the physical stimulation caused by the second ultrasound and high temperature/high pressure caused by collapse of the bubbles in order to accelerate release of the drug” are recitations of intended uses/functions/results or how the microbubbles or nanobbules are used and the result of hydrolysis of the ligand-drug ester bond, and thereby are immaterial to the patentability of the product (the claimed product of an ultrasound-assisted drug delivery carrier), as these intended uses/functions/results do not change the structure of the claimed product. As discussed above, the claimed structures of “an ultrasound-assisted drug delivery carrier comprising a ligand linked with a drug through an ester bond, a phospholipid, and a PEGylated phospholipid, wherein the drug delivery carrier is provided in a form of microbubbles or nanobubbles” have been taught by Tartis supra. Thus, 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. If the prior art structure is capable of performing the intended use, then it meets the claim. It is noted that structure dictates all properties/characteristics allegedly claimed. See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP §2112.01.
Regarding claim 2, as discussed above Tartis teaches the ligand is a phospholipid.
Regarding claim 7, Tartis teaches the phospholipid is selected from DPPC, DSPE, DMPE, and DOPE ([053]).
Regarding claim 8, Tartis teaches the microbubbles have a diameter between 0.5 µm to 10 µm ([028]).
As a result, the aforementioned teachings from Tartis are anticipatory to claims 1-2, 7-8, 11, and 13 of the instant invention.
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.
Claim(s) 1-4, 7-8, 11, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tartis et al (WO 2019/200043 A1), and further in view of Unger et al (6,231,834 B1).
The product-by-process claim interpretation applies here.
The drug delivery carrier of claims 1-2, 7-8, 11, and 13 are discussed above, said discussion being incorporated herein in its entirety.
However, Tartis does not teach the ligand is a biomaterial wherein the biomaterial is a protein or a biocompatible polymer of claims 3 and 4.
Regarding claims 3 and 4, Unger teaches a ultrasound-assisted drug delivery carrier in the form of microbubbles comprising albumin linked to a drug via an ester bond, and lipid composition containing DPPC, DPPA, and DPPE-PEG500 (columns 3, 5, 16, 17, 22-23, 28-35, 45-46, 48-50, 55, 70, and 80; claims 1-15).
It would have been obvious to one of ordinary skill in the art to modify the formulation of Tartis such that a polymer-drug conjugate such as albumin-drug conjugate is used as the drug-conjugate, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Tartis and Under are commonly drawn to ultrasound-assisted drug delivery carriers in the form of microbubbles containing ligand-drug conjugate, a phospholipid, and PEGylated phospholipid, wherein Unger provides of the use of an albumin-drug conjugate as the ligand-drug conjugate, as Unger indicated that aside from the lipid of Tartis, the drug can be also be conjugated with a protein such as albumin for effective targeted delivery of the drug (Unger: columns 3, 5, 13, 16, 17, 22-23, 28-35, 45-46, 48-50, 55, 70, and 80; claims 1-15). Thus, an ordinary artisan provided the guidance from Unger would have looked to other known biocompatible ligands in the art including protein such as albumin, so as to produce the ultrasound-assisted drug delivery carriers in the form of microbubbles that provide the desired targeted delivery of the drug, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the reference, especially in the absence of evidence to the contrary.
Claim(s) 1-2, 5-8, 11, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tartis et al (WO 2019/200043 A1), and further in view of James (US 2009/0221485 A1) and Unger et al (6,231,834 B1).
The product-by-process claim interpretation applies here.
The drug delivery carrier of claims 1-2, 7-8, 11, and 13 are discussed above, said discussion being incorporated herein in its entirety.
However, Tartis does not teach the amphipathic material of claims 5 and 6.
Regarding claims 5 and 6, James teaches alkyl-PEG-drug conjugate that increase amphiphilicity (Abstract; [0014]-[0024], [0060]-[0062], , [0068], [0071], [0077]-[0078], [0090], [0093]-[0096], [0098], [0100], [0491]). James teaches the alkyl-PEG-peptide conjugate is formed by linking the drug to the alkyl-PEG via an ester bond ([0078] and [0098]). James teaches the conjugated peptide has improve bioavailability, half-live of the peptide, and improved stability of the peptide, as well as, provides for a time-release or controlled release effect ([0020], [0072], [0078], [0488], [0491]; claim 2). James teaches the alkyl-PEG has from 2 to 15 polyethylene subunits and the alkyl moiety has 2 to 20 carbon atoms ([0093]), which overlaps the claimed polyethylene subunit (6 to 50) and carbon atoms of the alkyl (5 to 30). James that the number of PEG monomers and the length of the alkyl can be adjustable or varied to achieve the desired properties of hydrophilicity/hydrophobicity for the specific indication ([0068], [0071], and [0090]). Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results from the claimed parameters, the optimization of the number of PEG monomers and the length of the alkyl would have been obvious before the effective filing date of applicant's invention. “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP §2144.05 (I)-(II).
It would have been obvious to one of ordinary skill in the art to modify the formulation of Tartis such that a polymer-drug conjugate such as alkyl-PEG-peptide conjugate is used as the drug-conjugate, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because James indicated that the conjugation of drug (peptide) to an alkyl-PEG provide a resultant drug-conjugate or prodrug that has improved bioavailability, half-live of the peptide, and stability of the peptide, as well as, provides for a time-release or controlled release effect. Furthermore, Unger indicated that aside from the lipid of Tartis, the drug (peptide) can be also be conjugated with a biocompatible polymer such as PEG and PEG derivatives for effective targeted delivery of the drug (Unger: columns 3, 5, 13, 16, 17, 22-23, 28-35, 45-46, 48-50, 55, 70, and 80; claims 1-15). One of ordinary skill in the art would have reasonable expectation of success in modifying the formulation of Tartis such that a polymer-drug conjugate such as alkyl-PEG-peptide conjugate is used as the drug-conjugate because the objective of Tartis for using the drug-conjugate is to improve bioavailability and stability of the drug, as well as, provides for a time-release or controlled release effect to the desired target of the delivery, which is the same objectives achieve from using the drug-conjugate of James. Thus, an ordinary artisan provided the guidance from the cited prior arts would have looked to other known biocompatible ligands in the art including alkyl-PEG, so as to produce a drug delivery carrier that has improved bioavailability and stability of the drug, as well as, provides for a time-release or controlled release effect to the desired target of the delivery, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the reference, especially in the absence of evidence to the contrary.
Claim(s) 1-2, 7-8, 10-11, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tartis et al (WO 2019/200043 A1), and further in view of Mei et al (US 2020/0197534 A1).
The product-by-process claim interpretation applies here.
The drug delivery carrier of claims 1-2, 7-8, 11, and 13 are discussed above, said discussion being incorporated herein in its entirety.
However, Tartis does not teach the targeting agent is additionally introduced on a surface of the ligand or the phospholipid of claim 10.
Regarding claim 10, Mei teaches a pharmaceutical composition comprising a nanocarrier containing a ligand (phospholipid) conjugated to a drug via an ester bond, a phospholipid and a PEGylated phospholipid (Abstract; [0015], [0027]-[0046], [0092]-[0099], [0276]-[0277], [0356]-[0362] and [0448]; claims 1, 16, 18-20, 24-25, and 28-29). Mei teaches a targeting moiety is further conjugated to the phospholipid of the nanocarrier ([0067], [0069], [0070], [0114], [0117], [0119]-[0129], [0155], [0158], [0160]-[0161], [0262], [0484], [0486], [0493], and [0495]).
It would have been obvious to one of ordinary skill in the art to further introduce a targeting moiety on the surface of the phospholipid carrier of Tartis, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Mei provided the guidance to do by teaching that the a targeting moiety can be attached to the surface of a lipid nanocarrier so as to provide a drug delivery nanocarrier that has selective targeting or specific binding with receptors or other biomolecular components expressed on the cell surface of interest (Mei: [0262]). Thus, an ordinary artisan seeking to provide a drug delivery nanocarrier that has selective targeting or specific binding with receptors or other biomolecular components expressed on the cell surface of interest would have looked to further attaching a targeting moiety on the surface of the lipid nanocarrier of Tartis, per guidance from Mei, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the reference, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 06/23/2025 have been fully considered but they are not persuasive.
Applicant argues that Tartis “fails to disclose forming the bubbles by adding a sodium chloride aqueous solution and a 2H,3H-decafluoropentane to a ligand, phospholipid, and PEGylated phospholipid and by applying ultrasound.” Thus, Applicant alleges that Tartis “fails to teach or suggest "wherein the microbubbles or nanobubbles are formed by adding a sodium chloride aqueous solution and a 2H,3H- decafluoropentane to the ligand, phospholipid, and PEGylated phospholipid and applying first ultrasound thereto" recited in amended claim 1.” (Remarks, page 6).
In response, the Examiner disagrees. As discussed above in the pending 102 rejection, the recitation of “the microbubbles or nanobubbles are formed by adding a sodium chloride aqueous solution and a 2H,3H-decafluoropentane to the ligand, phospholipid, and PEGylated phospholipid and apply first ultrasound thereto” as recited in claim 1, is a recitation of a product-by-process.
As discussed above, the claimed structures of “an ultrasound-assisted drug delivery carrier comprising a ligand linked with a drug through an ester bond, a phospholipid, and a PEGylated phospholipid, wherein the drug delivery carrier is provided in a form of microbubbles or nanobubbles” have been taught by Tartis supra. The ultrasound-assisted drug delivery carrier of Tartis is structurally the same as the claimed ultrasound-assisted drug delivery carrier and thus, “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Accordingly, the teachings from Tartis remain to anticipate the claimed ultrasound-assisted drug delivery carrier of the amended, independent claim 1.
As a result, for at least the reason discussed above, claims 1-2, 7-8, 11, and 13 remain to be anticipated by the teachings from Tartis in the pending 102 rejection as set forth in this office action, as well as, dependent claims 3-6 and 10 remain to be render obvious by the combined teachings of the cited prior arts in the pending 103 rejections as set forth in this office action.
New Rejection
Necessitated by Applicant’s Claim Amendments
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-8, 10, 11 and 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.
Regarding claim 1, the terms “high temperature” and “high pressure” in claim 1 are relative terminologies which render the claim indefinite because it is unclear what temperature or pressure is considered “high temperature” or “high pressure, as “high temperature” and “high pressure” are not defined by the claim. The specification does not define the terms “high temperature” and “high pressure,” as well as, the specification does not provide a standard for ascertaining the requisite degree. Thus, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 2-8, 10, 11 and 13 are also rejected as they depend directly or indirectly from indefinite claim 1.
As a result, claims 1-8, 10, 11 and 13 do not clearly set forth the metes and bounds of patent protection desired.
Conclusion
No claim is 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.
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/DOAN T PHAN/ Primary Examiner, Art Unit 1613