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 .
Claims 1-21 and 23-30 are pending.
Claims 13 and 23 are amended.
Claim 22 is cancelled.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
Claims 1-9, 11-12 and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CHANDRA (Design of photocleavable lipids and their application in liposomal "uncorking". ChemComm. 2005.).
Regarding claim 1, CHANDRA teaches liposomes, which reads on lipid membrane-based carrier, that have a “triggered” release/lyse to deliver drugs to the body (Page 3021, paragraph 2). O-nitrobenzyl is attached to the membrane and the hydrophilic headgroup on it is cleaved upon irradiation, allowing the remaining nitroso benzaldehyde compound to trigger lysis (page 3021 paragraph 3, Page 3023 paragraph 2 and figure 3). This reads on a lysing agent (nitroso benzaldehyde) and a photolabile lytic blocking agent (hydrophilic headgroup) wherein the photolabile lytic blocking agent blocks lytic activity of the lysing agent until the photolabile lytic blocking agent is released from the photoactive composition upon exposure to the radiation.
Regarding claim 2, the O-nitrobenzyl, which is the combination of the lysing agent and lytic blocking agent, is coupled to the liposome (figure 3).
Regarding claim 3, the hydrophilic headgroup is cleaved upon irradiation, which is known as photocleavage (page 3021, paragraph 3). Which reads on the photolabile lytic blocking agent comprises a photolytic moiety.
Regarding claim 4, the hydrophilic headgroup prevents the nitroso benzaldehyde compound from triggering lysis (Page 3023 paragraph 2 and figure 3), which reads on the photolytic moiety blocks the lytic activity of the lysing agent.
Regarding claim 5 metal ions can be used within the composition (page 3021, paragraph 2).
Regarding claim 6, CHANDRA teaches liposomes which have a lipid bilayer.
Regarding claim 7-9, CHANDRA teaches that liposomes are used to deliver small molecule drugs, and/or DNA fragments (Page 3021, paragraph 1), which reads on biomolecules, such as nucleic acids.
Regarding claim 11 and 30, the lysing agent (nitroso benzaldehyde) and a photolabile lytic blocking agent (hydrophilic headgroup) are covalently coupled to one another (scheme 2).
Regarding claim 12, the photocleavage occurs using visible light (page 3021, paragraph 5).
Claims 1-4, 6-8, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by MIRANDA (Mechanisms of light0induced liposome permeabilization. Bioengineering and Translational Medicine. 2016).
Regarding claim 1, MIRANDA teaches light triggered liposomes that release drugs (page 267, abstract). The liposomes, which reads on lipid membrane-based carrier, has porphyrin-phospholipid (PoP) and unsaturated lipids independently attached to the membrane of the liposome (Page 269, figure 1). PoP prevents lysis until the liposome is irradiated (Page 269, figure 1 and page 268, paragraph 6). Once the PoP is irradiated, it produces reactive oxygen species that then allows the unsaturated lipids to preform lysis releasing the drug (Page 269, figure 1 and page 268, paragraph 6). The unsaturated lipids are the lysing agent, while the PoP is the lytic blocking agent.
Regarding claim 2, the PoP and unsaturated lipids are coupled to the membrane of the carrier (figure 1).
Regarding claim 3, the PoP when irradiated produces reactive oxygen species that then allows for lysis (Page 269, figure 1 and page 268, paragraph 6), which reads on a photolytic moiety.
Regarding claim 4, PoP prevents lysis until the liposome is irradiated (Page 269, figure 1 and page 268, paragraph 6), which reads on the photolytic moiety blocks the lytic activity of the lysing agent.
Regarding claim 6, the composition comprises a liposome (abstract), which reads on a lipid bilayer.
Regarding claim 7 and 8, the liposome delivers doxorubicin (page 268, paragraph 6), which reads on pharmaceutical compositions
Regarding claim 10, The liposomes, which reads on lipid membrane-based carrier, has porphyrin-phospholipid (PoP) and unsaturated lipids independently attached to the membrane of the liposome (Page 269, figure 1).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-9, 11-21, 24-29 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over CHANDRA (Design of photocleavable lipids and their application in liposomal "uncorking". ChemComm. 2005.) in view of LAWRENCE (U.S. 2016/0144031 A1).
CHANDRA does not teach having two therapeutic compositions.
Regarding claim 13, LAWRENCE teaches a photoactive composition (abstract) comprising red blood cells (abstract), which reads on lipid membrane-based carrier, a photolabile molecule (abstract), such as cobalamin (Page 1, paragraph 0008), that bonds to an active agent such as nucleic acids (page 2, paragraph 0017). The bond between the active agent and the photolabile molecule is broken when the compound is exposed to light (page 2, paragraph 0027), also called photocleavage. LAWRENCE further teaches a second photolabile molecule; a second bioactive agent that is appended to the photolabile molecule, wherein the second bioactive agent is released when exposed to a second wavelength of light, which reads on a first and second photoactive compositions have differing absorption spectra.
Regarding claim 14, LAWRENCE teaches that a plurality of compounds can be used, such as different active agents ((page 9, paragraph 0160), which reads on the first and second therapeutic agent are different.
Regarding claim 15, LAWRENCE teaches the administration site can be sequentially subjected to effects of different active agents in a predetermined sequence without having to administer compounds at multiple time points (page 9, paragraph 0160), which reads on two different therapeutic agents working in conjunction to treat a diseased condition in a patient. A subject can be treated by different active agents merely by adjusting the wavelength of the light that the administration site is exposed to without having to administer compounds at multiple time points. (page 9, paragraph 0160).
Regarding claim 16, LAWRENCE teaches a method of administering the compound and then exposing the compound to a certain wavelength of light to release the active agent (claim 17).
Regarding claim 24, LAWRENCE teaches that a second photoactive composition, with a second therapeutic agent can be added to the method to then be irradiated with light as well (claim 20).
Regarding claim 25, LAWRENCE teaches the compositions can be administered sequentially (paragraph 160).
Regarding claim 26, LAWRENCE teaches the compositions can also be administered simultaneously (paragraph 222).
Regarding claim 27, LAWRENCE teaches that the different active agents are individually released by adjusting the wavelength of the light (Page 9, paragraph 0160), which reads on having different absorption spectra.
Regarding claim 28, LAWRENCE teaches the administration site can be sequentially subjected to effects of different active agents in a predetermined sequence without having to administer compounds at multiple time points (page 9, paragraph 0160), which reads on two different therapeutic agents working in conjunction to treat a diseased condition in a patient.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate two photoactive compositions and to use the benefits of having two photoactive compositions. The person of ordinary skill in the art would have been motivated to make those modifications, because this allows a subject to be treated by different active agents by merely adjusting the wavelength of light the site is exposed to without the need for multiple injections at multiple time points, and reasonably would have expected success because all references are in the same field of endeavor, such as lipid membrane carriers that are used to deliver therapeutic agents to a subject utilizing photocleavage.
Regarding claim 17, as discussed above, CHANDRA teaches the O-nitrobenzyl, which is the combination of the lysing agent and lytic blocking agent, is coupled to the liposome membrane (figure 3).
Regarding claim 18-20, as discussed above, CHANDRA teaches that liposomes are used to deliver small molecule drugs, and/or DNA fragments (Page 3021, paragraph 1), which reads on biomolecules, such as nucleic acids and pharmaceutical compositions, such as small molecule drugs.
Regarding claim 21 and 29, LAWRENCE teaches lysing red blood cells/erythrocytes (page 11, paragraph 0175).
Claims 1-9, 11-21, 23, 25-29 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over CHANDRA (Design of photocleavable lipids and their application in liposomal "uncorking". ChemComm. 2005.) and LAWRENCE (U.S. 2016/0144031 A1) in view of BORMAN (Hitching a Ride on Red Blood Cells. Chemical and Engineering News. 2014.).
CHANDRA and LAWRENCE teach Applicant’s invention as discussed above.
CHANDRA and LAWRENCE do not teach using the liposome drug delivery system for thrombus.
Regarding claim 23, BORMAN teaches encapsulating drugs inside of red blood cells to treat various diseases such as thrombosis (paragraph 6), which is blood clots/thrombus. Using red blood cells to treat blood disorders is beneficial since red blood cells can persist in the bloodstream for weeks and allow for treatments over prolonged periods of time (paragraph 3).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate treating a blood disease such as thrombus. The person of ordinary skill in the art would have been motivated to make those modifications, because red blood cell carriers can persist weeks in the bloodstream leading to treatment for prolonged periods of time, and reasonably would have expected success because all references are in the same field of endeavor, such as delivering a drug using liposomes and LAWRENCE teaches using red blood cells.
Response to Arguments
Applicant argues that CHANDRA does fails to teach both a lysing agent and a photolabile lytic blocking agent where the lysing agent has lytic activity that is blocked prior to the release of the photolabile blocking agent. Instead, CHANDRA teaches an o-nitrobenzyl compound that has no existing component with lytic activity prior to any cleavage. The o-nitrobenzyl compound must follow photocleavage with "an electron-redistribution to form an aci-nitro form, which finally rearranges to form the o-nitroso benzaldehyde product." Chandra, page 3021. It is this product formed after photocleavage that has any lytic activity, and therefore there is no lytic activity to block by any alleged photolabile blocking agent of Chandra because a lysing agent does not exist prior to photocleavage. Therefore, Chandra fails to disclose each limitation of independent claim 1.
Examiner does not find Applicant’s argument persuasive because the term “blocked” in its broadest reasonable interpretation simply means that a component is acting as some form of prevention of lysis. As discussed above, O-nitrobenzyl is attached to the membrane and the hydrophilic headgroup on it is cleaved upon irradiation, allowing the remaining nitroso benzaldehyde compound to trigger lysis (page 3021 paragraph 3, Page 3023 paragraph 2 and figure 3). This reads on a lysing agent (nitroso benzaldehyde) and a photolabile lytic blocking agent (hydrophilic headgroup) wherein the photolabile lytic blocking agent blocks lytic activity of the lysing agent until the photolabile lytic blocking agent is released from the photoactive composition upon exposure to the radiation. The hydrophilic headgroup was preventing the O-nitrobenzyl from being able to transform to the final nitroso benzaldehyde compound which causes lysis, this reads on the broadest reasonable interpretation of “blocked”. The broad claim as written does not exclude extra steps in between the photocleavage and lysis, nor does it require any exact mechanism of action, but rather the broad interpretation of some component preventing lysis until being photoactivated which is taught by the prior art.
Furthermore, A 'whereby' clause (in this case “wherein”) that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim." Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1172 (Fed. Cir. 1993). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003). In the instant case the wherein clause merely characterizes the results of the components. The wherein clause does not impose any additional structural limitations in addition to a lysing agent and a photolabile blocking agent and recites how the composition would function upon exposure to radiation.
Applicant argues Miranda teaches a 1,2-dioleoyl-sn-glycem-3-phosphocholine (DOPC) component of a lipid membrane, which has no lytic activity prior to any photoactivation and therefore is not a lysing agent from which lytic activity can be blocked, as claimed. See Miranda, page 268, section 2.1. Only upon oxidation after photoactivation of porphyrin-phospholipid does DOPC undergo structural changes that allow for membrane permeabilization. See Miranda, page 268, section 2.1 and FIG. 1 B, reproduced below:
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Only following the oxidization shown in Miranda, FIG. 1 B above, is the DOPC able to cause membranes to form pores for release of components. Miranda, page 268, section 2.1. Therefore, Miranda lacks disclosure of a lysis agent that has blocked lytic activity until a photolabile lytic blocking agent is released, and fails to disclose each limitation of independent claim 1.
Examiner does not find Applicant’s argument persuasive because the term “blocked” in its broadest reasonable interpretation simply means that a component is acting as some form of prevention of lysis. As discussed above, the liposomes, which reads on lipid membrane-based carrier, has porphyrin-phospholipid (PoP) and unsaturated lipids independently attached to the membrane of the liposome (Page 269, figure 1). PoP prevents lysis until the liposome is irradiated (Page 269, figure 1 and page 268, paragraph 6). Once the PoP is irradiated, it produces reactive oxygen species that then allows the unsaturated lipids to preform lysis releasing the drug (Page 269, figure 1 and page 268, paragraph 6). The unsaturated lipids are the lysing agent, while the PoP is the lytic blocking agent. The PoP in its original form was preventing unsaturated lipids from being able to cause lysis, this reads on the broadest reasonable interpretation of “blocked”. The broad claim as written does not exclude extra steps in between the photocleavage and lysis, nor does it require any exact mechanism of action, but rather the broad interpretation of some component preventing lysis until being photoactivated which is taught by the prior art.
Furthermore, A 'whereby' clause (in this case “wherein”) that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim." Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1172 (Fed. Cir. 1993). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003). In the instant case the wherein clause merely characterizes the results of the components. The wherein clause does not impose any additional structural limitations in addition to a lysing agent and a photolabile blocking agent and recites how the composition would function upon exposure to radiation.
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. 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 SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
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/S.L.M./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618