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 1 – 12 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
For the purposes of applying prior art, the PCT application filing date of 02/05/2021 is applied.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the present specification includes amino acid sequences having four or more amino acids each (p. 3, formula (II – V)).
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specification
The use of the term affibody, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 1 and 4 are is objected to because of the following informalities:
Regarding claim 1, the preamble recites “a affibody-cytotoxin conjugate”. However, because “affibody” begins with a vowel, the article “a” should be replaced with “an”. Appropriate correction is required.
Regarding claim 4, “conjugation” on line 4 of claim 8 seems to be missing an article, such as “a”, before “conjugation”.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 – 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The following quotation from section 2163 of the Manual of Patent Examination Procedure (MPEP) is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice... reduction to drawings...or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See BU Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1 – 12 are rejected as lacking adequate descriptive support for a possession of an affibody-cytotoxin conjugate that may target any protein. The claims are directed to a genus of a generic structure of affibody-organic small molecule linker-cytotoxin, but the present specification does not provide a representative number of examples of such affibody-cytotoxin conjugates. The specification presents nine affibody-cytotoxin conjugates (nine embodiments; paragraphs 0050 – 0092 of the pre-grant publication), which does not cover the scope of the claimed structure of independent claim 1. Thus, the application fails to provide enough examples of species that may have any active targeting function within the claimed genus.
Regarding claim 5, although the claim provides structure for the linker and cytotoxin of the claimed affibody-cytotoxin conjugate, no structure is provided for the affibody portion of the affibody-cytotoxin conjugate, which provides the specificity for the target of the affibody-cytotoxin conjugate.
For example, the decision of Amgen v. Sanofi, 872, F.3d 1367 (Fed. Cir. 2017) supports expanded analysis of whether a claim drawn to an antibody being specific for an epitope, even a specific epitope, permits an applicant to pursue all possible antibodies that are capable of being produced against such an epitope. Presently, the claimed affibody-cytotoxin conjugate composition used is only defined by a generic structure without specificity recited in the claims. Thus, the claimed affibody-cytotoxin conjugate can bind any epitope of any target. In view of the fact patterns detailed in Amgen v. Sanofi, applicant is not in possession of such an affibody-cytotoxin conjugate that can bind to any epitope as presented by the present claims.
Providing SEQ ID NOs defining the affibody polypeptides for claims 1 – 12 can provide sufficient structures of the claimed affibody-cytotoxin conjugate.
In view of this uncertainty and the absence of a representative number of examples of the claimed genus, the claims are rejected for lack of adequate written description support.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 – 12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 – 8 and 10 each recites “affibody” which is a trademarked term. The claim scope is uncertain since the trademark or trade name cannot be used properly to describe any particular material or product. The use of a trademark or trade name in a claim to describe a material or product would not only render a claim indefinite, but would also constitute an improper use of the trademark or trade name. See MPEP 2173(u).
Furthermore, present claim 1 recites “mainly comprising” at the end of the first line to the beginning of the second line. Under MPEP 2173.02, claims must inform those skilled in the art regarding the scope of the invention with "reasonable certainty." However, “mainly” is a relative term, and thus the boundaries of the structure of the claimed affibody-cytotoxin conjugate are not clear.
Claim 1 also recites the limitation “the organic small molecule linker” in the last line. There is insufficient antecedent basis for this limitation in the claim.
Claims 5 and 6 also each recites the limitation “the conjugate” in line 2 of each claim. There is insufficient antecedent basis for this limitation in each claim.
Claim 8 also recites the limitation "the nanoparticle" in line 1; “the affibody-cytotoxin conjugate” in lines 1, 5, and 7; “the hydrophobic cytotoxin” in line 3; and “the small molecule linker” in line 4. There are insufficient antecedent bases for these limitations in the claim.
Claim 9 depends from claim 8 and thus inherits the deficiencies of claim 8.
Claims 10 – 12 each recites “application”. However, the term is not defined in the claims, and it is not clear what “application” refers to. For example, claim 10 recites “[a]n application of the affibody-cytotoxin conjugate for active targeted therapy of tumors according to claim1, in preparing drugs for active targeted therapy of tumors.” It is not clear if claim 10 is directed to a method of treating or a method of making.
Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). See MPEP 2173.05 (q). Thus claims 10 – 12 are indefinite because they do not clearly set forth any steps involved in the processes of preparing drugs.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ALTAI (Altai M, et al. Affibody-derived drug conjugates: Potent cytotoxic molecules for treatment of HER2 over-expressing tumors. J Control Release. 2018 Oct 28;288:84-95; an IDS reference submitted 02/09/2023).
The present application is directed to an affibody-cytotoxin conjugate for active targeted therapy of tumors, mainly comprising a cytotoxin and an affibody with active targeting function, the conjugate being obtained by covalent coupling the cytotoxin and the affibody through a small molecule
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linker;
wherein A is the affibody, L is the organic small molecule linker, and * is the cytotoxin.
According to the present specification, in the production of embodiment 2 of 9 affibody-cytotoxin conjugates defined, N2′-deacetyl-N2′-(3-Mercapto-1-oxopropyl) maytansine (DM1, 737 0.2 mg) and ethylbismaleimide (1.1 g) [cytotoxin and small molecule, respectively] are added in a reaction flask to produce the intermediate B-1, which is then reacted with the affibody ZHER2:342 obtain the final product ZHER2:343-DMI (paragraphs 0061 – 0065 of the pre-grant publication). The final product is assumed to have the general structure of the claimed affibody-cytotoxin conjugate of present claim 1.
ALTAI is directed to an affibody molecule targeting HER2, ZHER2:2891, conjugated with the cytotoxic maytansine derivate MC-DM1, for targeted cancer therapy: the affibody drug conjugate (ZHER2:2891)2-ABD-MC-DM1. See abstract. ALTAI teaches that the structure of an antibody drug conjugate (ADC) in an affibody drug conjugate (AffDC), where the antibody of the ADC is replaced with an affibody and linked by an organic small molecule linker. See Introduction, paragraphs 1 – 4 and Fig. 1C. Thus, ALTAI teaches the affibody-linker-cytotoxin of present claim 1.
Regarding claim 3, ALTAI teaches the cytotoxin maytansine derivative MC-DM1. See abstract and Fig. 1C..
Regarding claim 10, ALTAI teaches the preparation of the affibody-cytotoxin conjugate for active targeted therapy of tumors. See abstract and 2. Materials and methods, pgs. 85 – 87. However, it is noted that a wherein clause in a method claim is not given patentable weight when it simply expresses the intended result of a process step positively recited. See MPEP 2111.04.
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 – 3 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over ABRAHMSÉN (US 2013/0280164 A1, published 10/24/2013; see PTO-892: Notice of References Cited).
ABRAHMSÉN is directed to new polypeptides which bind to Human Epidermal Growth Factor Receptor 2 (HER2) and the use of a HER2 binding polypeptide as a diagnostic agent and/or medicament, more particularly use thereof as a diagnostic agent and/or medicament for diagnosis and/or treatment of forms of cancer characterized by over-expression of HER2. See paragraph 001. ABRAHMSÉN teaches that the HER2-binding polypeptides is an Affibody® molecule, which is coupled to the linker Maleimide-DOTA (see paragraph 0131), then coupled to a radiolabel (see paragraph 0134) or using other organic small molecule linkers (See paragraphs 0070-0073) . Because ABRAHMSÉN also teaches that the HER2 binding polypeptide (affibody) may be conjugated to a label, a chelator, a therapeutic and/or diagnostic agent (see paragraph 0074) or additional therapeutic moieties like the cytotoxins ricin A, Pseudomonas exotoxin, calcheamicin, or maytansinoids (see paragraph 0043), it would have been obvious to replace the radiolabel or conjugate it in combination with a therapeutic agent such as a cytotoxin (see paragraph 0043), and it would have been obvious to produce the affibody-small molecule linker-cytotoxin of present claim 1 from the teachings of ABRAHMSÉN.
Regarding claim 2, ABRAHMSÉN teaches the Affibody® molecule Z00342 (sometimes also called ZHER2:342). See paragraph 0144.
Regarding claim 3, ABRAHMSÉN teaches that the affibody may be coupled with toxins, such as ricin A, Pseudomonas exotoxin, calcheamicin, maytansinoid; toxic small molecules, such as auristatin analogs, doxorubicin. See paragraph 0043.
Regarding claim 10, ABRAHMSÉN teaches the treatment of cancer characterized by overexpression of HER2. See abstract.
Claims 4 – 5 are rejected under 35 U.S.C. 103 as being unpatentable over ALTAI as applied to claims 1, 3, and 10 above, and further in view of YAGHOUBI (Yaghoubi, S. et al. Development and biological assessment of MMAE-trastuzumab antibody–drug conjugates (ADCs). Breast Cancer 28, 216–225 (2021); published 09/05/2020; see PTO-892).
The teachings of ALTAI with regard to the claims are discussed above and are fully incorporated here.
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YAGHOUBI is directed to trastuzumab-based antibody drug conjugate (ADC) to enhance the biopharmaceutical profile of trastuzumab. See Abstract: Background. YAGHOUBI teaches the following structure:
See Fig. 1 on p. 220. Thus, YAGHOUBI teaches the small molecule linker of formula (IV) of present claim 4 (which is MC-VC-PAB, according to YAGHOUBI) and teaches the small-molecule-linker-cytotoxin of the third, fifth, seventh, and ninth structures (from top to bottom) of present claim 5. The difference between YAGHOUBI’s structure and that of present claim 5 is that YAGHOUBI’s structure is of an antibody-small molecule linker-cytotoxin or antibody drug conjugate (ADC) and not of an affibody-small molecule linker-cytotoxin (affibody drug conjugate, according to ALTAI’s abstract). However, ALTAI teaches that antibodies and affibodies share similarities in that they both bind their targets with high specificity and are effective in treating cancer (see p. 85, left column, paragraphs 1 – 2 and p. 93, left column, second paragraph). Thus, it would have been obvious to one having ordinary skill in the art to modify ALTAI’s affibody structure with the linker-cytotoxin of YAGHOUBI’s ADC. There would have been a reasonable expectation of success considering that affibodies have been shown to be target proteins and peptides with high affinity and specificity and that the claimed small molecule linker and cytotoxin have been known to be used in ADCs that have also been effective at treating tumors as evidenced by the applied art.
Claims 6 – 7 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over ALTAI as applied to claims 1, 3, and 10 above in further view of ALEXIS (Alexis F, et al. HER-2-targeted nanoparticle-affibody bioconjugates for cancer therapy. ChemMedChem. 2008 Dec;3(12):1839-43; see PTO-892).
The teachings of ALTAI with regard to the claims are discussed above and are fully incorporated here.
ALEXIS is directed to drug delivery vehicles comprised of polymeric nanoparticles (NPs) that are surface modified with Affibody ligands that bind to the extracellular domain of the trans-membrane human epidermal growth factor receptor 2 (HER-2) for targeted delivery to cells which over express the HER-2 antigen. See abstract. ALEXIS teaches that to develop HER-2 targeted drug encapsulated NPs, we conjugated the anti-HER-2 Affibody to the thiol-reactive maleimide of the PLA-PEG-Maleimide (PLA-PEG-Mal) (See page 3-1st and 2nd paragraphs). ALEXIS teaches the copolymers of the nanoparticles (NPs) form negatively charged NPs with a core-shell structure in an aqueous environment via the nanoprecipitation method. The hydrophobic core of the NPs is capable of carrying pharmaceuticals, especially those with poor water solubility (See page 3- 2nd paragraph). Thus, ALEXIS teaches Affibody-small molecule linker-NP in an aqueous solution. Although the paclitaxel inside the NP is a cytotoxin, it does not seem to be attached to the affibody-small molecule linker. Nonetheless, ALTAI anticipates the affibody-small molecule linker-cytotoxin structure of claim 1 as discussed above. Thus, it would have been obvious to use ALTAI’s structure in a nanoparticle. There would have been a reasonable expectation of success considering that ALEXIS teaches an affibody-small molecule-NP structure that contains cytotoxin that increases drug efficacy, lowers drug toxicity, and maintains a relatively high concentration of drug at the site of interest, especially for the treatment of cancer and ALTAI’s affibody-small molecule linker-cytotoxin structure is also effective at treating cancer.
Regarding claim 6, because ALTAI in view of ALEXIS teaches the structure of the nanoparticle of the an affibody-cytotoxin conjugate, this structure would inherently be obtained by the self-assembly of the affibody-cytotoxin conjugate.
Regarding claim 7, ALEXIS teaches that the nanoparticle's size diameter (< 100 nm) and the Affibody conjugation on the surface of the nanoparticle. See Figure 1 and caption, p. 8. ALEXIS’ Fig. 1 also shows the cytotoxin paclitaxel in the core of the NP. Thus, ALEXIS renders the limitations of claim 7 obvious.
Regarding claim 11, ALEXIS teaches the development HER-2 targeted drug encapsulated NPs. See abstract and p. 3, first paragraph. However, it is noted that a wherein clause in a method claim is not given patentable weight when it simply expresses the intended result of a process step positively recited. See MPEP 2111.04.
Claims 6, 7, 8 – 9 11, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over ALEXIS in view of YAGHOUBI as applied to claims 1, 3-5, and 10 above and MARTÍNEZ RIVAS (Claudia Janeth Martínez Rivas, et al. Nanoprecipitation process: From encapsulation to drug delivery, International Journal of Pharmaceutics, Volume 532, Issue 1, 2017, Pages 66-81; see PTO-892).
The teachings of ALEXIS and YAGHOUBI with regard to the claims are discussed above and are fully incorporated here.
MARTÍNEZ RIVAS is directed to the nanoprecipitation technique for formation of nanoparticles, which has been used in the pharmaceutical and agricultural research as clean alternative for other drug carrier formulations. See abstract.
Regarding claim 7, MARTÍNEZ RIVAS teaches making nanoparticles of less than 200 nm in diameter. See p. 76-right col., last paragraph and p. 78 right col., 1st full paragraph.
Regarding claim 8, ALTAI teaches conjugation of the affibody with MC-DM1 (See p. 85-Section 2.3 and Fig, 1) and YAGHOUBI teaches that the linker MC-VC-PAB-MMAE was conjugated to trastuzumab through sulfhydryl groups to produce MMAE-trastuzumab ADCs. See Fig. 1. Considering that both ALEXIS’s NP-Affibody bioconjugate and YAGHOUBI’s ADC are effective at treating tumors, it would have been obvious to use ALEXIS’s affibody with YAGHOUBI’s small molecule linker and cytotoxin in ALEXIS’s NP that may be produced using the preparation method for a nanoparticle of an affibody-cytotoxin conjugate of claim 8.
Regarding part (2) of claim 8, ALEXIS teaches the HER-2 targeted drug encapsulated NPs involves the nanoprecipitation method. According to MARTÍNEZ RIVAS, in the nanoprecipitation method, solvent and nonsolvent phases preparation is required which is followed by the addition of one phase to another under moderate magnetic stirring, then organic solvent evaporation at ambient temperature or with a rotavapor allows the obtaining of nanoparticles (NPs) suspension in water. MARTÍNEZ RIVAS teaches that the solvent phase comprises one or more organic solvents and that solvent and nonsolvent phases are usually named as organic and aqueous phases, respectively. See 4. Nanoprecipitation, p. 68 and Fig. 2. MARTÍNEZ RIVAS further teaches that the most used solvents in nanoprecipitation method are ethanol, acetone, hexane, methylene chloride or dioxane and that non-solvent (or aqueous phase) is mostly water. See p. 68, right column, last paragraph. Thus, MARTÍNEZ RIVAS teaches part (2) of claim 8.
Regarding claim 9, as discussed above, MARTÍNEZ RIVAS teaches that one of the most used organic solvent in nanoprecipitation method is ethanol. See p. 68, right column, last paragraph.
Regarding claim 12, MARTÍNEZ RIVAS teaches that production of NPs for the treatment of tumors. See p. 72, right column, third paragraph. However, it is noted that a wherein clause in a method claim is not given patentable weight when it simply expresses the intended result of a process step positively recited. See MPEP 2111.04.
Conclusion
No claim is allowed.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646