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 .
Status of the Claims
Claims 22-23, 27-28, 30, and 32-42 are pending and under current examination. Claims 24-26, 29, and 31 are cancelled.
Withdrawn Claim Objections and Rejections
All rejections pertaining to claims 24-26, 29, and 31 are moot because the claims are cancelled in the amendments to the claims filed 1/16/2026.
All objections pertaining to claim 33 are withdrawn in view of the amendments to the claims filed 1/16/2026.
All rejections not reiterated have been withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s amendments to the claims filed 1/26/2026 have necessitated the new grounds of rejection.
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 22-23, 27-30, 32, 34-39, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Lakshmanan et. al. (Nature Protocols, pg. 2050-2080, publication year: 2017, cited in the IDS filed 5/19/2022, of record) in view of Unger (U.S. Patent Application No. 2001/0018072, publication date: 8/30/2001, of record) and Ibsen et. al. (Drug Design, Development and Therapy, pg. 375-388, publication year: 2013, of record).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 22 and 23, Lakshmanan teaches that gas vesicles harvested from the cyanobacterium Anabaena flos-aquae (Ana) comprise a protein shell enclosing a hollow gas-filled interior (pg. 2050, Introduction-Development of the protocol). Lakshmanan teaches that the gas vesicles have a hydrodynamic diameter of about 200nM (pg. 2050 Development of the protocol).
Regarding claim 27, Lakshmanan teaches the relevant limitations of claim 22 above.
Regarding claim 28, Lakshmanan teaches that the gas vesicles have a hydrodynamic diameter of about 200nM (pg. 2050 Development of the protocol).
Regarding claims 30, 32, and 37 Lakshmanan teaches that gas dissolved in the media surrounding the algae partitions freely in and out of the protein shell of the gas vesicle (pg. 2050, Development of the protocol).
Regarding claim 34, Lakshmanan teaches that the modified algae-derived gas vesicles may be used in clinical diagnostics (pg. 2050 Introduction).
Regarding claim 35, Lakshmanan teaches that the algae-derived gas vesicle may be used for in vivo ultrasound imaging at OD500,ps of about 25 (pg. 2067, Ultrasound imaging of GVs in vivo, step (ix)).
Regarding claims 36, 38, and 39 Lakshmanan teaches the relevant limitations of claim 22 above.
Regarding claim 42, Lakshmanan teaches the relevant limitations of claim 22 and 27 above.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 22 and 27, Lakshmanan does not teach that the algae-derived gas vesicle may be encapsulated in a liposome consisting of DOPC and DSPE-PEG or a size of the gas vesicle. However, this deficiency is cured by Unger and Ibsen.
Unger teaches that the target gas vesicles may have one or more monolayers and they may be concentric. The vesicles include such entities as liposomes and protein-coated bubbles. The vesicles may encapsulate gases and may comprise a targeting ligand [0033]. The lipids used to form the targeted gas vesicles may include DOPC, DSPE, lipids bearing polymers such as PEG, and any combinations thereof [0108] and may act as stabilizing materials [0031]. Unger also teaches that the stabilizing agents may either form or stabilize the vesicles, in either way serving to minimize or substantially prevent the escape of gases until said release is desired [0031]. The gas filled vesicles may be less than about 1µm in size [0204]. Ibsen teaches that microbubbles may be encapsulated inside liposomes to protect the microbubble and to ensure the microbubble actuation releases the entire payload. The nested structure presents a smooth outer surface which increases stability of the particle and reduces immune recognition (pg. 382 Microbubble-based drug delivery vehicle designs and Fig. 9F).
Regarding claim 28, Lakshmanan does not teach the zeta potential of the modified gas vesicles.
Regarding claim 30, 32, 37, and 39 Lakshmanan does not teach that the internal gas of the algae-derived gas vesicle is oxygen. However, this deficiency is cured by Unger.
Unger teaches that preferred gases for the gas vesicle are inert and biocompatible, such as nitrogen, carbon dioxide, and oxygen [0162].
Regarding claim 35, Lakshmanan does not teach the effective concentration of modified gas vesicle embraced by the instant claim.
Regarding claims 36, 38, and 39, Lakshmanan does not teach the use of the modified gas vesicle in the diagnosis of any cancers embraced by the instant claims. However, this deficiency is cured by Unger
Unger teaches that the region of a patient to be treated by the disclosed gas vesicle includes diseased tissue, including cancerous tissue and tumors, and that region can be imaged with diagnostic imaging [0043 and 0062]. Unger also teaches that the therapeutic included in the disclosed gas vesicle may include therapeutics to treat malignant melanoma or kidney cancer [0138].
Regarding claim 37, Lakshmanan does not teach the used of the modified gas vesicle in a pharmaceutical composition. However, this deficiency is cured by Unger.
Unger teaches that the therapeutic incorporated into the gas vesicle may be used in the treatment of a malady, affliction, disease, or injury in a patient [0045]. The Examiner considers Unger to therefore read on the limitation “a pharmaceutical composition” embraced by the instant claim 37.
Regarding claim 42, Lakshmanan does not teach a molar ratio of DOPC to DSPE-PEG in the modified gas vesicle. However, this deficiency is cured by Unger.
Unger teaches that the PEG moiety surrounds the vesicle membrane or skin, and thereby forms a physical barrier to various enzymatic and other endogenous agents in the body whose function is to degrade such foreign materials. DPPE-PEG may provide more vesicles of a smaller size which are safe and stable to pressure when combined with other lipids. The pegylated material, because of its structural similarity to water, may be able to defeat the action of the macrophages of the human immune system, which would otherwise tend to surround and remove the foreign object. The result is an increase in the time during which the stabilized vesicles may function as diagnostic imaging contrast media [0101].
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 22 and 27, it would have been prima facie obvious to one of ordinary skill in the art of filing to encapsulate the algae-derived gas vesicle embraced by Lakshmanan in a liposome consisting of DOPC and DSPE-PEG. One would have understood in view of Unger that a targeted gas vesicle may contain more than one concentric layer and that one of those layers may be comprised of lipids, including a combination of DOPC and PEG-modified DSPE[0108], that may act as a stabilizing agent to regulate the release of gases [0031] and in view of Ibsen that microbubbles encapsulated in a liposome increases stability of the particle and reduced immune recognition (pg. 382 Microbubble-based drug delivery vehicle designs and Fig. 9F). It would have been obvious to encapsulate the gas vesicle embraced by Lakshmanan in such a liposome. One of ordinary skill in the art of filing would have been motivated to encapsulate the gas vesicle embraced by Lakshmanan in the liposome embraced by Unger and Ibsen in order to improve the stability of the algae-derived gas vesicle. The artisan of ordinary skill would have had reasonable expectation of success because Ibsen teaches targeted gas vesicles encapsulated in liposomes.
Regarding claims 22 and 28, the particle size and zeta potential are clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal particle size and zeta potential of the modified gas vesicles in order to best achieve the desired results as such would provide advantageous therapeutic effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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, 105 USPQ 233 (CCPA 1955). In the instant case, Lakshmanan teaches that conventional imaging agents based on microbubbles are limited by size and physical instability (pg. 2050, Introduction). The Examiner considers it prima facie obvious to optimize the particle size and zeta potential of the modified gas vesicles embraced by Lakshmanan to lie within the range embraced by the instant claims, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the particle size and zeta potential would directly impact the stability of the vesicles and ability to label the desired target and therefore be an optimizable variable.
Regarding claim 30, 32, and 37, and 39 it would have been prima facie obvious to one of ordinary skill in the art of filing that the oxygen in the gas vesicle embraced by Lakshmanan may be oxygen. One would have understood in view of Unger that a targeted gas vesicle may encapsulate an inert biocompatible gas such as oxygen. It would have been obvious to one of ordinary skill in the art of filing to include a biocompatible gas such as oxygen in the gas vesicles embraced by Lakshmanan. One of ordinary skill in the art of filing would have been motivated to include oxygen in the gas vesicles embraced by Lakshmanan in order to provide the therapeutic benefits of the oxygen to the tissues targeted by the gas vesicles. The artisan of ordinary skill would have had reasonable expectation of success because Unger teaches that targeted gas vesicles may comprise oxygen as the encapsulated gas. See MPEP 2144.07.
Regarding claim 35, the effective concentration of modified gas vesicle used as a diagnostic agent is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of modified gas vesicle in order to best achieve the desired results as such would provide advantageous diagnostic effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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, 105 USPQ 233 (CCPA 1955). In the instant case, Lakshmanan teaches that the signal rendered by the modified gas vesicles is dependent on the concentration of gas vesicles used as a contrast agent and may be modified by raising or lowering the concentration of gas vesicles (pg.2075, Table 5). The Examiner considers it prima facie obvious to optimize the concentration of gas vesicle used as a diagnostic agent, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the concentration of gas vesicle used as a diagnostic agent is directly correlated to a signal rendered by the gas vesicle and therefore be an optimizable variable.
Regarding claims 36, 38, and 39 it would have been prima facie obvious to one of ordinary skill in the art of filing that the diagnostic modified gas vesicle embraced by Lakshmanan may be used to target kidney cancer or malignant melanoma. One would have understood in view of Unger that a gas vesicle may be used to target the treatment of kidney cancer and malignant melanomas. It would have been obvious that the algae-derived gas vesicles embraced by Lakshmanan may also be used in diagnostic imaging of the same regions. One of ordinary skill in the art of filing would have been motivated to utilize the gas vesicles embraced by Lakshmanan in the diagnosis of kidney cancer and malignant melanomas in order to provide a more targeted diagnostic method. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Unger teaches that modified gas-vesicles of similar structure to those embraced by Lakshmanan may be used to target kidney cancer and malignant melanomas.
Regarding claim 37, it would have been prima facie obvious to one of ordinary skill in the art of filing that the algae-derived gas vesicle embraced by Lakshmanan may be used in a pharmaceutical composition. One would have understood in view of Unger that a similar modified gas vesicle may be combined with a therapeutic agent to target specific cancers. It would have been obvious to include a therapeutic agent with the gas vesicle embraced by Lakshmanan. One of ordinary skill in the art of filing would have been motivated to include a therapeutic agent with the gas vesicle embraced by Lakshmanan in order to provide additional therapeutic benefit to the specific tissue targeted by the gas vesicle. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Unger teaches that modified gas vesicles may incorporate therapeutics targeting specific cancers.
Regarding claim 42, the molar ratio of DOPC and DSPE-PEG is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal molar ratio in order to best achieve the desired results as such would provide advantageous size and stability effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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, 105 USPQ 233 (CCPA 1955). In the instant case, Unger teaches that the pegylated lipid has a direct effect on the size and stability of the gas vesicles [0101]. The Examiner considers it prima facie obvious to optimize the molar ratio of lipids encapsulating the gas vesicle , absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the amount of pegylated lipid would have a direct effect on the size and stability of the gas vesicles and therefore be an optimizable variable.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Lakshmanan et. al. (Nature Protocols, pg. 2050-2080, publication year: 2017, cited in the IDS filed 5/19/2022, of record) in view of Unger (U.S. Patent Application No. 2001/0018072, publication date: 8/30/2001, of record) and Ibsen et. al. (Drug Design, Development and Therapy, pg. 375-388, publication year: 2013, of record), as applied to claims 22-23, 27-30, 32, 34-39, and 42 above, and further in view of Arpicco et. al. (Molecules, pg. 3193-3230, publication year: 2014, of record) and Choi et. al. (ACS Nano, pg. 8591-8599, publication year: 2011, of record).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Lakshmanan, in view of Unger and Ibsen, teaches the relevant limitations of claim 22 and 27 above. Lakshmanan also teaches that the exterior of the gas vesicle may be modified via chemical conjugation of chemical moieties, such as polymers, to the lysine residues on the protein shells of the gas vesicles (pg. 2053, Modification and functionalization of GVs) and that gas dissolved in the media surrounding the algae partitions freely in and out of the protein shell of the gas vesicle (pg. 2050, Development of the protocol).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Lakshmanan does not teach a hyaluronic acid covalently conjugated to the exterior surface of the protein shell and PEG covalently conjugated to the hyaluronic acid. However, this deficiency is cured by Arpicco and Choi.
Arpicco teaches that nanoparticles may be modified by EDC-coupling of hyaluronic acid to the surface (pg. 3201, 4.1 Polymeric Nanoparticles and pg. 3204 Table 2). Arpicco also teaches that hyaluronic coating naturally targets particles to cells expressing specific receptors and gives particles stealth properties (pg. 3201, 4. HA Decorated Particles). Choi teaches that hyaluronic acid nanoparticles accumulate in the liver. Choi also teaches that PEGylation of the hyaluronic nanoparticles effectively reduce liver uptake and increase the circulation time in the blood, leading to selective accumulation of the nanoparticles to the tumor site (pg. 8592, Introduction).
Lakshmanan does not teach that the internal gas of the algae-derived gas vesicle is oxygen. However, this deficiency is cured by Unger.
Unger teaches that preferred gases for the gas vesicle are inert and biocompatible, such as nitrogen, carbon dioxide, and oxygen [0162].
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art of filing to include a PEG moiety covalently bound to a hyaluronic acid moiety that is covalently bound to the protein surface of the gas vesicle embraced by Lakshmanan. One would have understood in view of Arpicco that hyaluronic acid may be covalently attached to particles in order to target the particles to cells expressing specific receptors (pg. 3201, 4. HA Decorated Particles) and in view of Choi that PEGylation of hyaluronic acid nanoparticles reduces liver uptake of the nanoparticles and increases the circulation time in the blood, leading to selective accumulation of the nanoparticles to the tumor site (pg. 8592, Introduction). It would have been obvious to modify the surface of the algae-derived gas vesicle embraced by Lakshmanan with a PEG-modified hyaluronic acid moiety. One of ordinary skill in the art of filing would have been motivated to conjugate a PEG-modified hyaluronic acid moiety to the surface of the algae-derived gas vesicle in order to reduce liver uptake and increase circulation time and targeting of the gas vesicle. The artisan of ordinary skill would have had reasonable expectation of success because Lakshmanan teaches that gas vesicles may be modified by chemical conjugation to polymers (pg. 2053, Modification and functionalization of GVs).
It would have been prima facie obvious to one of ordinary skill in the art of filing that the oxygen in the gas vesicle embraced by Lakshmanan may be oxygen. One would have understood in view of Unger that a targeted gas vesicle may encapsulate an inert biocompatible gas such as oxygen. It would have been obvious to one of ordinary skill in the art of filing to include a biocompatible gas such as oxygen in the gas vesicles embraced by Lakshmanan. One of ordinary skill in the art of filing would have been motivated to include oxygen in the gas vesicles embraced by Lakshmanan in order to provide the therapeutic benefits of the oxygen to the tissues targeted by the gas vesicles. The artisan of ordinary skill would have had reasonable expectation of success because Unger teaches that targeted gas vesicles may comprise oxygen as the encapsulated gas. See MPEP 2144.07.
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Lakshmanan et. al. (Nature Protocols, pg. 2050-2080, publication year: 2017, cited in the IDS filed 5/19/2022, of record) in view of Unger (U.S. Patent Application No. 2001/0018072, publication date: 8/30/2001, of record) and Ibsen et. al. (Drug Design, Development and Therapy, pg. 375-388, publication year: 2013), as applied to claims 22-23, 27-30, 32, 34-39, and 42 above, and further in view of Sachar et. al. (Journal of Pharmacology and Experimental Therapeutics, pg. 267-275, publication year: 2016, of record).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Lakshmanan, in view of Unger and Ibsen, teaches the relevant limitations of claims 22 and 39 above.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Lakshmanan does not teach that the modified algae-derived gas vesicles may be co-administered with protoporphyrin IX. However, this deficiency is cured by Sachar.
Sachar teaches that a stable precursor for protoporphyrin IX can be administered orally or locally as a therapy for early malignant lesions of the skin, bladder, breast, stomach, and oral cavity. The photodynamic effects of protoporphyrin IX may also be used for cancer diagnosis (pg. 272, PPIX-Based Strategies for Diagnosis and Therapy).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to combine two compositions, each of which is taught by the prior art to be useful for the same purpose (modified gas vesicles and protoporphyrin IX for photodynamic cancer therapy and imaging), in order to form a third composition to be used for the very same purpose. See MPEP 2144.06-I.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Lakshmanan et. al. (Nature Protocols, pg. 2050-2080, publication year: 2017, cited in the IDS filed 5/19/2022, of record) in view of Unger (U.S. Patent Application No. 2001/0018072, publication date: 8/30/2001, of record) and Ibsen et. al. (Drug Design, Development and Therapy, pg. 375-388, publication year: 2013), as applied to claims 22-23, 27-30, 32, 34-39, and 42 above, and further in view of Zhu et. al. (Methods in Enzymology, pages 267-274; publication year: 2013, of record).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Lakshmanan teaches that the algae-derived gas vesicles may be prepared by first lysing collected cultures of Anabaena flos-aquae, isolating the gas vesicles by centrifugation, and resuspending in PBS for use and storage (pg. 2059, steps (xii-xvii)).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Lakshmanan does not teach that the algae-derived gas vesicles may be combined with a solution of DOPC and DSPE-PEG in chloroform to form a liposome. However, this deficiency is cured by Unger and Zhu.
Unger teaches that the gas vesicles may be prepared by suspension of the surfactant, such as a lipid, in an organic solvent, followed by evaporation of the solvent, resuspension in an aqueous suspension, sonication and centrifugation [0188]. Zhu teaches that lipids may first be dissolved in chloroform when forming lipid vesicles (pg. 270, section 4.2).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to utilize the aqueous solution of gas vesicle isolated by the method embraced by Lakshmanan in the method of forming lipid gas vesicles embraced by Unger. One would have understood in view of Unger and Zhu that the lipids intended to form a liposome gas vesicle may first be dissolved in an organic solvent such as chloroform and then resuspended in an aqueous suspension. It would have been obvious that DOPC and DSPE-PEG combined in chloroform may then be added to the aqueous suspension of gas-vesicles obtained by the method embraced by Lakshmanan. One of ordinary skill would have been motivated to combine the two methods in order to produce a lipid-encapsulated algae-derived gas vesicle. The artisan of ordinary skill would have had reasonable expectation of success because Unger teaches that lipids dissolved in an organic solvent may be combined, the solvent evaporated, and then resuspended in an aqueous solution to form a gas vesicle.
Response to Arguments
Applicant's arguments filed 1/16/2026 have been fully considered but they are not persuasive.
On page 8, Applicant argues that Unger teaches that the lipid composition of the vesicles comprise a neutral lipid, a negatively charged lipid, and a lipid bearing a stabilizing material, and therefore does not read on the amended claims. This is not found persuasive. In response, simply because the prior art “discloses a multitude of effective combinations does not render any particular formulation less obvious." Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). "[P]icking and choosing may be entirely proper in the making of a 103, obviousness rejection." In re Arkley, 455 F.2d 586, 587 (CCPA 1972). Unger teaches that the lipids used to form the targeted gas vesicles may include DOPC, DSPE, lipids bearing polymers such as PEG, and any combinations thereof [0108]. The existence of a preferred embodiment, as cited by Applicant in Unger [0100 and 0101], does not constitute a teaching away from a broader disclosure or nonpreferred embodiments. See MPEP 2123. Therefore, the argument is not persuasive and the rejection is maintained.
On page 9, Applicant argues that the modified gas vesicles of the present invention have an average particle size of 290-330nm and can remain stable over six months, which is significantly improved and unexpected over Unger. This is not found persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In response to the alleged unexpected results, please refer to MPEP 716.02 (b) which details the burden on Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, Applicant must establish that differences in results are in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims.
Differences in results are in fact unexpected and unobvious: The evidence of unexpected results amounts to stability of the lipid vesicles over six months. However, Unger teaches that the stability of vesicles may be attributable, at least in part, to the materials from which the vesicles are made and it is often not necessary to employ additional stabilizing materials [0098]. Unger teaches that the lipids used to form the targeted gas vesicles may include DOPC, DSPE, lipids bearing polymers such as PEG, and any combinations thereof [0108]. Furthermore, the algae derived gas vesicle taught by Lakshmanan is identical to the algae derived gas vesicle embraced by the instant claims. Therefore, the stability of the gas vesicles is not unexpected over the prior art because Lakshmanan in view of Unger teaches a nearly identical gas vesicle and therefore, the stability properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Differences are of both practical and statistical significance: The evidence of unexpected results amounts to the stability of the lipid gas vesicles; therefore the differences are of practical significance. However, the data presented in Figure 1 and in paragraphs 74 and 75 shows no difference in stability between native and surface-modified gas vesicles. Therefore, the differences are not of statistical significance.
Evidence of unexpected properties must be in commensurate scope with the claims: The evidence of unexpected results is in regards to the stability of the lipid-modified gas vesicles. Therefore, the evidence of unexpected properties is in commensurate scope with the claims.
Additionally, no side-by-side comparison to the closest prior art is provided to establish unexpectedly superior performance. There is no nexus between the purportedly unexpected property and the differences between the instant invention, as claimed, and the closest prior art. Thus, the Applicant’s argument is not persuasive and the rejection is maintained.
On page 9, Applicant argues that Unger fails to provide any hint or suggestion to select DOPC or DSPE-PEG to modify gas vesicles to form modified gas vesicles with the same small size and long-term stability as claimed. This is not found persuasive. This is not found persuasive. In response, simply because the prior art “discloses a multitude of effective combinations does not render any particular formulation less obvious." Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). "[P]icking and choosing may be entirely proper in the making of a 103, obviousness rejection." In re Arkley, 455 F.2d 586, 587 (CCPA 1972). Furthermore, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., long-term stability) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
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.
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ELIZABETH ANNE MEYERSExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614