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 Application
Claims 1-14 are under examination.
Drawings
The drawings are objected to because of the following informalities:
Figures 1-4 axes are blurry, small font, and difficult to read.
Figure 5 ICG and ICG-DOPE, and ICG-diSA and ICG-diDSPE cannot be distinguished from each other.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because there are three paragraphs (Problem, Solutions, and Selected Drawing). A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Interpretation
Claim 6 recites “additionally fixes or supports at least one drug.” While the specification mentions the same wording of “fixes or supports” (pg 11, para [0014], lines 1-2), the examiner notes that the specification does not further clarify what is encompassed by fixes or supports at least one drug. Therefore, for the purposes of examining, the examiner interprets “additionally fixes or supports” as meaning there is a drug fixed to the lipid-based particle or supported in any way by the lipid-based particle. For the purposes of examination, the examiner interprets any prior art containing at least one drug in the particle in any way as reading on this limitation.
Claims 4-10 recite “lipid-based particle”. The examiner notes that the specification defines “lipid-based particle” as a particle containing a plurality of lipids physically bonded to each other by intermolecular forces (pg 17, para [0019], lines 7-10). Therefore, for the purposes of examination, the examiner interprets any prior art containing any plurality of lipids with intermolecular forces among them as reading on this claim limitation.
Claim 8 recites neutral lipids. The examiner notes that the specification defines neutral lipid is one that is neutral at physiological pH in either uncharged form or neutral amphoteric ion (pg 37, para [0054], lines 1-2). For the purposes of examination, the examiner interprets any prior art containing a lipid which meets this criteria as reading on this 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.
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.
Claim(s) 1-5 and 8-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mizusawa, K.; et al., US 10,655,059 B2 and Hayashi, H.; et al., US 9,302,018 B2.
Mizusawa, K.; et al. (hereafter referred to as Mizusawa) is drawn to compounds for optical imaging with molecular weight and polyethylene glycols bonded to specific cyanine pigment through a linker (title; abstract). Mizusawa teaches an optical imaging method known for non-invasively visualizing information inside a living body (col 1, lines 21-24) and acoustic waves and fluorescence emitted from light-absorbing body and can irradiate a light which can be measured enabling imaging (col 1, lines 25-28) and that indocyanine green (ICG) s useful as a pigment absorbing light in a near-infrared wavelength region and emitting fluorescent or acoustic waves (col 1, lines 28-33) which makes ICG useful as a contrast agent for optical imaging (col 1, lines 32-34). Mizusawa teaches low molecular weight pigments are quickly discharged from the body so it is useful to bond something to the ICG, such as a polymer, to reduce clearance enabling increased tumor uptake (col 1, lines 35-43). Mizusawa teaches a series of compounds according to the formula I, reproduced below (col 2, formula 1), where R101 to R112 are independently hydrogen atoms, halogens, acetoxy groups, alkyl groups, alkyl esters, alkylamides (col 7, lines 34-41) and R11 to R14 are each alkyl, fluorinated alkyl (col 7, lines 42-47), and L11 to L17 can be substituted or unsubstituted methines (col 7, lines 47-55), A11 to A14 are each alkylene or fluorinated alkylene (col 7, lines 59-67) and Q11 to Q12 can be CONT-, NTCO-, NT(C=O)NT-, -NT(C=S)NT-, NT(C=O)O-, -O-, -S-, -S(O)2NT-, OP(=O)(OH)-, -S-S-, CT=N-, -CT=N-NH-, -CT=N-O-, CT=N-NH-O- (col 8, lines 23-33), and B11 to B12 can independently be -H, -OCH3, NH2, -OH, -CO2H, -S(=O)2OH, -P(=O)(OH)2, and -OP(=O)(OH)2 (col 8, lines 59-62). Mizusawa teaches the synthesis (col 19, lines 43-67; col 20, lines 19-38).
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As to claim 1, Mizusawa teaches formula (A) (col 9, formula I-1), where R1 and R2 are each independently represent –(CH2)k-CONH-R3 (col 9, formula I-2), where k is 2 (col 9, Formula I-2).
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Mizusawa does not teach R3 represents a group selected from the group consisting of –(CH2)m-OPO3—CH2-CH(CH2OCOR4)(OCOR5), branched-chain C14 to C40 alkyl, and branched-chain C14 to C40 alkenyl, where m is 2-4, where R4 and R5 each independently represent straight-chain or branched-chain C13 to C21 alkyl or straight-chain or branched-chain C13 to C21 alkenyl.
Hayashi, H.; et al. (hereafter referred to as Hayashi) is drawn to fluorescent probe for imaging lymph nodes using a liposome (title; abstract). Hayashi teaches sentinel lymph nodes directly receive the flow of lymph from the primary lesion of a tumor and are believed to be the location where lymph node metastasis first occurs (col 1, lines 18-21) and identifying the sentinel lymph node using a dye or radioactive colloid, excising the lymph node during surgery, examining for the presence or absence of metastasis, and then determining the resection range based on that result enables unnecessary removal of lymph nodes in the case where evidence of metastasis is not found (col 1, lines 23-32). Hayashi teaches that identification of the lymph node is achieved through administration of a dye or radioactive colloid into the periphery of the tumor, and then monitoring the migration of the dye or radioactive colloid (col 1, lines 32-36) and indocyanine dyes are useful for detecting sentinel lymph nodes using near-infrared fluorescent pigment (col 2, lines 25-27) while dyes such as indocyanine green are useful, they can diffuse too quickly (col 1, lines 40-49) and detecting a lymph node using an aqueous solution o indocyanine green, has a rapid decrease in the fluorescence intensity (col 2, lines 52-63). Hayashi teaches a way to is better by incorporating into a liposome wand the result is increase fluorescence intensity , anchoring time in the sentinel lymph node becomes longer enabling useful detection of sentinel lymph nodes (col 3, lines 20-30) and Hayashi teaches the probes can be according to general Formula (I) (col 3, formula (I)) or particular embodiment Formula (VII), reproduced below (col 9, formula (VII)), where R1 and R2 are hexanoyl group, octanoyl group, decanoyl group, dodecanoyl group, tetradecanoyl group, hexadecanoyl group, octadecanoyl group, oleyl group, linoleyl group, linolenyl group, ricinoleyl group, geranyl group, geranylgeranyl group, farnesyl group, phytyl group or phytanyl group (col 9, lines 33-38). Hayashi teaches synthesis (col 31, synthetic scheme) and various specific embodiments of the ICG (claim 3 and claim 13).
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Regarding R3 groups, Hayashi teaches R3 represents –(CH2)m-OPO3—CH2-CH(CH2OCOR4)(OCOR5), where m is 2 (col 50, claim 13), where m is 2 (col 50, claim 13), where R4 and R5 are independently represent straight-chain C17 alkenyl (col 50, claim 13).
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It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to substitute the substituents of indocyanine green of Mizusawa with the substituents as taught by Hayashi because the substituted components and their functions were known in the art and a person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have yielded the predictable outcome of phospholipid substituents on indocyanine green.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the phospholipid substituents of Hayashi in place of each polymer substituents of Mizusawa because the prior art of Mizusawa disclosed indocyanine green clears from the body too quickly and introducing substituents, such as PEG improves the tumor uptake and imaging (col 1, lines 35-43). Additional prior art of Hayashi suggested phospholipid substituents to have similar properties of improving tumor uptake and retention and imaging enhancement (col 3, lines 20-30) because of the overlap in adding a group to the indocyanine green sulfate position between them involves known chemistry.
The skilled artisan would have been motivated to substitute the phospholipid substituents of Hayashi in place of the PEG substituents of Mizusawa because the phospholipid substituents enable the ICG to be loaded into liposomes more easily and even insert into the membrane of the tumor which could improve detection. Therefore, it would have been prima facie obvious to combine the teachings of Mizusawa with Hayashi.
As to claim 2, Mizusawa teaches R1 and R2 are each –(CH2)2-CONH-R3 (col 9, formula I-2).
Mizusawa does not teach R3 represents –(CH2)m-OPO3—-CH2-CH(CH2OCOR4)(OCOR5), where R4 and R5 are each independently straight-chain C13 to C21 alkyl or alkenyl and m is 2-4.
Hayashi teaches R3 is –(CH2)m-OPO3—CH2-CH(CH2OCOR4)(OCOR5), (col 41, synthetic scheme; col 50, claim 13), where R4 and R5 are each independently straight-chain C17 alkenyl and m is 2 (col 50, claim 13).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to substitute the substituents of indocyanine green of Mizusawa with the substituents as taught by Hayashi because the substituted components and their functions were known in the art and a person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have yielded the predictable outcome of phospholipid substituents on indocyanine green.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the phospholipid substituents of Hayashi in place of each polymer substituents of Mizusawa because the prior art of Mizusawa disclosed indocyanine green clears from the body too quickly and introducing substituents, such as PEG improves the tumor uptake and imaging (col 1, lines 35-43). Additional prior art of Hayashi suggested phospholipid substituents to have similar properties of improving tumor uptake and retention and imaging enhancement (col 3, lines 20-30) because of the overlap in adding a group to the indocyanine green sulfate position between them involves known chemistry.
The skilled artisan would have been motivated to substitute the phospholipid substituents of Hayashi in place of the PEG substituents of Mizusawa because the phospholipid substituents enable the ICG to be loaded into liposomes more easily and even insert into the membrane of the tumor which could improve detection. Therefore, it would have been prima facie obvious to combine the teachings of Mizusawa with Hayashi.
As to claim 3, Mizusawa teaches instant claim Formula (II) from instant claim Formula (A), where R1 and R2 are each –(CH2)2-CONH-R3 (col 9, formula I-2).
Mizusawa does not teach R3 represents –(CH2)m-OPO3—-CH2-CH(CH2OCOR4)(OCOR5), where R4 and R5 are each independently straight-chain C13 to C21 alkyl or alkenyl and m is 2-4.
Hayashi teaches R3 is –(CH2)m-OPO3—CH2-CH(CH2OCOR4)(OCOR5), (col 41, synthetic scheme; col 50, claim 13), where R4 and R5 are each independently straight-chain C17 alkenyl and m is 2 (col 50, claim 13).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to substitute the substituents of indocyanine green of Mizusawa with the substituents as taught by Hayashi because the substituted components and their functions were known in the art and a person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have yielded the predictable outcome of phospholipid substituents on indocyanine green.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the phospholipid substituents of Hayashi in place of each polymer substituents of Mizusawa because the prior art of Mizusawa disclosed indocyanine green clears from the body too quickly and introducing substituents, such as PEG improves the tumor uptake and imaging (col 1, lines 35-43). Additional prior art of Hayashi suggested phospholipid substituents to have similar properties of improving tumor uptake and retention and imaging enhancement (col 3, lines 20-30) because of the overlap in adding a group to the indocyanine green sulfate position between them involves known chemistry.
The skilled artisan would have been motivated to substitute the phospholipid substituents of Hayashi in place of the PEG substituents of Mizusawa because the phospholipid substituents enable the ICG to be loaded into liposomes more easily and even insert into the membrane of the tumor which could improve detection. Therefore, it would have been prima facie obvious to combine the teachings of Mizusawa with Hayashi.
As to claim 4, Mizusawa teaches instant claim Formula (II) from instant claim Formula (A), where R1 and R2 are each –(CH2)2-CONH-R3 (col 9, formula I-2).
Mizusawa does not teach R3 represents –(CH2)m-OPO3—-CH2-CH(CH2OCOR4)(OCOR5), where R4 and R5 are each independently straight-chain C13 to C21 alkyl or alkenyl and m is 2-4.
Mizusawa does not teach a lipid-based particles comprising a compound according to instant claim formula (A).
Hayashi teaches R3 is –(CH2)m-OPO3—CH2-CH(CH2OCOR4)(OCOR5), (col 41, synthetic scheme; col 50, claim 13), where R4 and R5 are each independently straight-chain C17 alkenyl and m is 2 (col 50, claim 13).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to substitute the substituents of indocyanine green of Mizusawa with the substituents as taught by Hayashi because the substituted components and their functions were known in the art and a person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have yielded the predictable outcome of phospholipid substituents on indocyanine green.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the phospholipid substituents of Hayashi in place of each polymer substituents of Mizusawa because the prior art of Mizusawa disclosed indocyanine green clears from the body too quickly and introducing substituents, such as PEG improves the tumor uptake and imaging (col 1, lines 35-43). Additional prior art of Hayashi suggested phospholipid substituents to have similar properties of improving tumor uptake and retention and imaging enhancement (col 3, lines 20-30) because of the overlap in adding a group to the indocyanine green sulfate position between them involves known chemistry.
The skilled artisan would have been motivated to substitute the phospholipid substituents of Hayashi in place of the PEG substituents of Mizusawa because the phospholipid substituents enable the ICG to be loaded into liposomes more easily and even insert into the membrane of the tumor which could improve detection. Therefore, it would have been prima facie obvious to combine the teachings of Mizusawa with Hayashi.
Regarding the lipid-based particle, Hayashi teaches a lipid-based particle comprising ICG-based compounds (abstract; col 3, lines 31-35; claim 15)
As to claim 5, Mizusawa teaches instant claim Formula (II) from instant claim Formula (A), where R1 and R2 are each –(CH2)2-CONH-R3 (col 9, formula I-2).
Mizusawa does not teach R3 represents –(CH2)m-OPO3—-CH2-CH(CH2OCOR4)(OCOR5), where R4 and R5 are each independently straight-chain C13 to C21 alkyl or alkenyl and m is 2-4.
Hayashi teaches R3 is –(CH2)m-OPO3—CH2-CH(CH2OCOR4)(OCOR5), (col 41, synthetic scheme; col 50, claim 13), where R4 and R5 are each independently straight-chain C17 alkenyl and m is 2 (col 50, claim 13).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to substitute the substituents of indocyanine green of Mizusawa with the substituents as taught by Hayashi because the substituted components and their functions were known in the art and a person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have yielded the predictable outcome of phospholipid substituents on indocyanine green.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the phospholipid substituents of Hayashi in place of each polymer substituents of Mizusawa because the prior art of Mizusawa disclosed indocyanine green clears from the body too quickly and introducing substituents, such as PEG improves the tumor uptake and imaging (col 1, lines 35-43). Additional prior art of Hayashi suggested phospholipid substituents to have similar properties of improving tumor uptake and retention and imaging enhancement (col 3, lines 20-30) because of the overlap in adding a group to the indocyanine green sulfate position between them involves known chemistry.
The skilled artisan would have been motivated to substitute the phospholipid substituents of Hayashi in place of the PEG substituents of Mizusawa because the phospholipid substituents enable the ICG to be loaded into liposomes more easily and even insert into the membrane of the tumor which could improve detection. Therefore, it would have been prima facie obvious to combine the teachings of Mizusawa with Hayashi.
As to claim 8, Hayashi teaches the lipid-based particle further comprises sterols (col 33, lines 7-8) or polyethylene glycol-modified lipids (col 33, lines 21-23).
As to claim 9, Hayashi teaches a average particle diameter of 100-300 nm. The claimed range of 30-200 nm overlaps with the prior art range of 100-300 nm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 10, Hayashi teaches a liposome (abstract; col 33, lines 9-50; claim 15).
Claim(s) 6-7 and 11-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mizusawa and Hayashi as applied to claims 1-5 and 8-10 above, and further in view of Yang, J.; et al., US 9,717,686 B2.
The teachings of Mizusawa and Hayashi as applied in the previous rejection are incorporated in this rejection.
As to claim 6, Hayashi teaches a lipid-based particle comprising ICG-based compounds (abstract; col 3, lines 31-35; claim 15)
The combined teachings of Mizusawa and Hayashi do not teach the lipid-based particle supports at least one drug.
Yang, J.; et al. (hereafter referred to as Yang) is drawn to liposome compositions for cancer therapy (title; abstract). Yang teaches liposomes can be used as effective drug delivery vehicles and commercially available liposomal products have been developed for treatment of diseases such as cancer (col 1, lines 29-32) and liposomes typically contain a phospholipid bilayer separating an interior aqueous phase from the external aqueous environment so that it can carry hydrophobic and hydrophilic cargo (col 1, lines 29-41) and can accumulate in tumors as a means for localizing the drug in the tumor (col 1, lines 42-52). Yang teaches a variety of therapeutic or anti-cancer drugs can be used for the type of cancer or tumor (col 8, lines 47-59) and some anticancer drugs can be avastin or doxorubicin or others (col 8, lines 60-67) and the liposomes can have diagnostic agents included such as fluorescent agents, phosphorescent agents, chemiluminescent agents (col 13, lines 9-13) and indocyanine green is used when excitation and emission wavelengths of the optical agent fall in the near-infrared range (col 14, lines 13-18). Yang teaches these liposomes may be used in pharmaceutical compositions (col 15, lines 10-16; col 16, lines 6-14) and can be administered to the subject (col 2, lines 9-15; col 3, lines 47-54; col 33, claim 1).
Regarding a lipid-based particle that supports at least one drug, Yang teaches a lipid-based particle (a liposome) that supports an anti-cancer drug (col 8, lines 47-67).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the liposome of Hayashi to include a drug as taught by Yang because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of drug-loaded liposome.
A person of ordinary skill in the art would have had a reasonable expectation of success in having a liposome which supports a drug because the prior art of Hayashi disclosed liposomes known to be able to include indocyanine green (col 50, claim 15) or compounds within them (col 1, 60-66). Additional prior art of Yang suggested liposomes to have similar inclusion of indocyanine green (col 14, lines 13-18) and other compounds (col 8, lines 47-59) because of the overlap of liposomal structure between them involves known chemistry.
The skilled artisan would have been motivated to modify the liposomes of Hayashi and Mizusawa because including a drug into the detectable liposomes would enable monitoring of the location and effect of the drug in the subject. Therefore, it would have been prima facie obvious to combine the teachings of Mizusawa and Hayashi with Yang.
As to claim 7, Yang teaches the drug is an anticancer agent (col 8, lines 60-67).
As to claim 11, Yang teaches a pharmaceutical composition (col 15, lines 10-16; col 16, lines 6-14).
As to claim 12, Hayashi teaches a method of fluorescence imaging comprising administering to a subject the pharmaceutical composition (col 45, lines 29-51, example 5).
As to claim 13, Yang teaches a pharmaceutical composition comprising a lipid-based particle (col 15, lines 10-16; col 16, lines 6-14).
As to claim 14, Hayashi teaches a method of fluorescence imaging comprising administering to a subject the pharmaceutical composition comprising a lipid-based particles (col 45, lines 29-51, example 5).
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 9,957,392 B2 in view of Mizusawa, Hayashi, and Yang. The teachings of Mizusawa, Hayashi, and Yang as applied in the previous rejection are incorporated in this rejection.
Instant claims are drawn to a compound according to formula (A) and Formulae (I) or (II) included into a lipid-based particle which can include at least one drug or anti-cancer drug and contains polyethylene glycol-modified lipids, and sterols. And the lipid-based particle has a diameter of 30-200 nm and is either a micelle or a liposome. And the compound is in a pharmaceutical composition; and, a method of fluorescence imaging comprising administering to a subject the pharmaceutical composition of the compound.
The conflicting claims of U.S. Patent No. 9,957,392 B2 (hereafter referred to as '392) is drawn to a fluorescent probe for near-infrared fluorescent imaging comprising a liposome containing a fluorescent dye with a particle diameter of 100-300 nm and a method for identifying sentinel lymph nodes comprising administering to the subject the fluorescent probe and detecting fluorescence.
The conflicting claims of '392 do not teach formula (A).
The conflicting claims of ‘392 do not teach Formulae (I) or (II).
The conflicting claims of ‘392 do not teach at least one drug or anti-cancer drug.
The conflicting claims of ‘392 do not teach a liposome containing polyethylene glycol-modified lipids or sterols.
The conflicting claims of ‘392 do not teach pharmaceutical composition.
Regarding the compound according to formula (A), Mizusawa teaches formula (A) (col 9, formula I-1), where R1 and R2 are each independently represent –(CH2)k-CONH-R3 (col 9, formula I-2), where k is 2 (col 9, Formula I-2).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of conflicting claims of ‘392 to include the substituents of the compound as taught by Mizusawa because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of indocyanine green of the conflicting claims of ‘392 modified with the substituents of Mizusawa.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the indocyanine green of the conflicting claims of ‘392 because the conflicting claims of ‘392 disclosed indocyanine green with substituents known to work well for detection. Additional prior art of Mizusawa suggested indocyanine green with different substituents and a substituent on each ring portion of indocyanine green to have similar fluorescent detection properties because of the core indocyanine green structure between them involves known chemistry.
The skilled artisan would have been motivated to modify the substituents of the conflicting claims with linkers of Mizusawa because two substituents coming off the indocyanine green were shown to improve the tumor uptake. Therefore, it would have been prima facie obvious to combine the teachings of the conflicting claims of ‘392 with Mizusawa.
Mizusawa does not teach R3 represents a group selected from the group consisting of –(CH2)m-OPO3—CH2-CH(CH2OCOR4)(OCOR5), branched-chain C14 to C40 alkyl, and branched-chain C14 to C40 alkenyl, where m is 2-4, where R4 and R5 each independently represent straight-chain or branched-chain C13 to C21 alkyl or straight-chain or branched-chain C13 to C21 alkenyl.
Regarding R3 groups, Hayashi teaches R3 represents –(CH2)m-OPO3—CH2-CH(CH2OCOR4)(OCOR5), where m is 2 (col 50, claim 13), where m is 2 (col 50, claim 13), where R4 and R5 are independently represent straight-chain C17 alkenyl (col 50, claim 13).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to substitute the substituents of indocyanine green of the conflicting claims of ‘392 and Mizusawa with the substituents as taught by Hayashi because the substituted components and their functions were known in the art and a person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have yielded the predictable outcome of phospholipid substituents on indocyanine green.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the phospholipid substituents of Hayashi in place of each polymer substituents of the conflicting claims of ‘392 and Mizusawa because the prior art of the conflicting claims of ‘392 and Mizusawa disclosed indocyanine green clears from the body too quickly and introducing substituents, such as PEG improves the tumor uptake and imaging (col 1, lines 35-43). Additional prior art of Hayashi suggested phospholipid substituents to have similar properties of improving tumor uptake and retention and imaging enhancement (col 3, lines 20-30) because of the overlap in adding a group to the indocyanine green sulfate position between them involves known chemistry.
The skilled artisan would have been motivated to substitute the phospholipid substituents of Hayashi in place of the PEG substituents of the conflicting claims of ‘392 and Mizusawa because the phospholipid substituents enable the ICG to be loaded into liposomes more easily and even insert into the membrane of the tumor which could improve detection. Therefore, it would have been prima facie obvious to combine the teachings of the conflicting claims of ‘392 and Mizusawa with Hayashi.
Regarding formulae (I) or (II), Mizusawa teaches instant claim Formula (II) from instant claim Formula (A), where R1 and R2 are each –(CH2)2-CONH-R3 (col 9, formula I-2).
Mizusawa does not teach R3 represents –(CH2)m-OPO3—-CH2-CH(CH2OCOR4)(OCOR5), where R4 and R5 are each independently straight-chain C13 to C21 alkyl or alkenyl and m is 2-4.
Hayashi teaches R3 is –(CH2)m-OPO3—CH2-CH(CH2OCOR4)(OCOR5), (col 41, synthetic scheme; col 50, claim 13), where R4 and R5 are each independently straight-chain C17 alkenyl and m is 2 (col 50, claim 13).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to substitute the substituents of indocyanine green of the conflicting claims of ‘392 and Mizusawa with the substituents as taught by Hayashi because the substituted components and their functions were known in the art and a person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have yielded the predictable outcome of phospholipid substituents on indocyanine green.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the phospholipid substituents of Hayashi in place of each polymer substituents of the conflicting claims of ‘392 and Mizusawa because the prior art of the conflicting claims of ‘392 and Mizusawa disclosed indocyanine green clears from the body too quickly and introducing substituents, such as PEG improves the tumor uptake and imaging (col 1, lines 35-43). Additional prior art of Hayashi suggested phospholipid substituents to have similar properties of improving tumor uptake and retention and imaging enhancement (col 3, lines 20-30) because of the overlap in adding a group to the indocyanine green sulfate position between them involves known chemistry.
The skilled artisan would have been motivated to substitute the phospholipid substituents of Hayashi in place of the PEG substituents of the conflicting claims of ‘392 and Mizusawa because the phospholipid substituents enable the ICG to be loaded into liposomes more easily and even insert into the membrane of the tumor which could improve detection. Therefore, it would have been prima facie obvious to combine the teachings of the conflicting claims of ‘392 and Mizusawa with Hayashi.
Regarding at least one drug or anti-cancer drug, Yang teaches a lipid-based particle (a liposome) that supports an anti-cancer drug (col 8, lines 47-67).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the liposome of the conflicting claims of ‘392 and Hayashi to include a drug as taught by Yang because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of drug-loaded liposome.
A person of ordinary skill in the art would have had a reasonable expectation of success in having a liposome which supports a drug because the prior art of the conflicting claims of ‘392 and Hayashi disclosed liposomes known to be able to include indocyanine green (col 50, claim 15) or compounds within them (col 1, 60-66). Additional prior art of Yang suggested liposomes to have similar inclusion of indocyanine green (col 14, lines 13-18) and other compounds (col 8, lines 47-59) because of the overlap of liposomal structure between them involves known chemistry.
The skilled artisan would have been motivated to modify the liposomes of the conflicting claims of ‘392 and Hayashi and Mizusawa because including a drug into the detectable liposomes would enable monitoring of the location and effect of the drug in the subject. Therefore, it would have been prima facie obvious to combine the teachings of the conflicting claims of ‘392 and Mizusawa and Hayashi with Yang.
Regarding a liposome containing polyethylene glycol-modified lipids and sterols, Hayashi teaches the lipid-based particle further comprises sterols (col 33, lines 7-8) or polyethylene glycol-modified lipids (col 33, lines 21-23).
Regarding a pharmaceutical composition, Yang teaches a pharmaceutical composition (col 15, lines 10-16; col 16, lines 6-14).
Conclusion
No claims allowed.
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/EVAN M LEWOCZKO/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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