DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions. Claims included in the prosecution are claims 17 and 30-48.
Claim Objections
Claim 31 is objected to because of the following informalities: “wherein the liposome comprises the molecules comprising gemicitabine” should be recited as ---wherein the liposome comprises gemcitabine as the molecules --- to be less wordy. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 17 and 30-44 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.
Claim 17 recites the limitation "the submicron structure" in line 1. There is insufficient antecedent basis for this limitation in the claim. It is not clear what submicron structure the claim is referring to when there are no preceding limitations describing a submicron structure. To obviate this issue, it is suggested for the claim to recite “a submicron structure.”
Claim 17 recites a silica body defining a plurality of pores. The claim is indefinite since the term “defining” means to state or describe exactly the nature, scope or meaning of, and when put in context with the claim, the term makes the claim confusing. To obviate this issue, it is suggested for the claim to recite a silica body comprising a plurality of pores.
Claim 32 recites at least about 20% gemcitabine/lipid (wt/wt). The claim is indefinite since claim 17 recites wherein the molecules are in the plurality of pores and does not recite wherein the molecules are in the phospholipid bilayer. Therefore, it is unclear how there is an amount of gemcitabine per lipid.
Claim 33 recites a gel-like precipitate. The claim is indefinite since it is unclear how the term “like” modifies the otherwise definite term “gel.” Since the term is not necessary to an understanding of the claimed subject matter, the examiner recommends deleting it.
The term “substantial loss” in claim 38 is a relative term which renders the claim indefinite. The term “substantial loss” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear what degree of loss would be considered “substantial.” Although the specification discloses on page 10, lines 1-2 wherein substantial loss can refer to a loss of 10% or less, 5% or less, or 2% or less, it is not clear what range of loss is within the scope of the claim.
Claim 46 recites the limitation "the lipid bilayer.” There is insufficient antecedent basis for this limitation in the claim. Claim 17 does not recite a lipid bilayer. It is not clear whether the lipid bilayer is referring to the phospholipid bilayer of claim 17 or to a lipid bilayer in addition to the phospholipid bilayer recited in claim 17. If the former, the claim would not be further limiting claim 17.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 45 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 45 fails to further limit the subject matter of the claim upon which it depends since it depends from itself.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 17, 30, 38-43 and 46 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Lopez et al. (US 2004/0005352, Jan. 8, 2004) (hereinafter Lopez) (of record).
Lopez discloses a membrane-enclosed mesoporous silica microsphere that incorporate biological or biochemical functionality, either by inclusion within a mesoporous microsphere matrix, or in or on a supported, tethered or untethered lipid bilayer on the surface (¶ [0048]). The microsphere has mesopores that are enclosed by a lipid bilayer (¶ [0050]). At least one of said enclosed mesoporous spaces contain a biomolecule (claim 15). Biomolecules that may be contained in the encapsulated spaces of the microsphere includes pharmaceuticals (¶ [0069]). The mesoporous microsphere may have phospholipid bilayers (¶ [0114], [0115], [0117] and [0118]). Unbound phospholipid and unsequestered dye are removed by repeated centrifugation and resuspension in buffer (¶ [0114]). The pores may be used to accommodate functional biomolecules and probe molecules (i.e., claimed at least one additional agent) (¶ [0117]). The term “microsphere” refers to a sphere or bead having a diameter of 10 nm – 1 mm (¶ [0035]).
Lopez anticipates the instant claims insofar as disclosing a mesoporous silica microsphere (i.e., claimed silica body having a plurality of pores), biomolecules contained in the mesoporous spaces, and a phospholipid bilayer enveloping the microspheres.
In regards to instant claim 17 reciting the active method steps of providing, loading, and forming, in order to have a mesoporous silica microsphere, one must be provided; in order to have biomolecules contained in the mesoporous spaces, biomolecules must be loaded in the mesoporous spaces; and in order to have a phospholipid bilayer enveloping the microspheres, a phospholipid bilayer on the surface of silica body must be formed.
In regards to instant claim 30 reciting a liposome, a spherical-shaped vesicle that is composed of one or more phospholipid bilayers is a liposome. Therefore, the mesoporous silica microsphere enveloped by a phospholipid bilayer taught by Lopez is a liposome.
In regards to instant claims 38 and 39 reciting wherein the submicron structure retains the molecules within the submicron structure for at least 1 day without a substantial loss and wherein the substantial loss comprises a loss of 10% or less of the molecules retained within the submicron structure, respectively, the instant specification discloses on page 9, lines 29-32 that a phospholipid bilayer can stably seal the plurality of pores. In other words, submicron structures can retain molecules within the pores for extended periods of time without substantial losses. Therefore, since the mesoporous spaces of the mesoporous silica microsphere of Lopez are covered by a phospholipid bilayer liked the claimed invention, one of ordinary skill in the art would reasonably expect that the mesoporous silica microsphere of Lopez retains the molecules without substantial loss.
In regards to instant claims 40-43 reciting wherein the submicron structure is formulated for administration to a subject for treating cancer, this is merely a recitation of the intended use the submicron structure. The instant claims are method of making claims and are not method of using claims. Since Lopez discloses substantially the same submicron structure as the claimed invention, the submicron structure of Lopez is capable of being used in the manner recited in instant claims 40-43, whether Lopez discloses such use or not.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
1. Claims 31, 32, 34-37, 44, 45 and 48 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lopez et al. (US 2004/0005352, Jan. 8, 2004) (hereinafter Lopez) (of record) in view of Frese et al. (Cancer Discovery, 2012) (hereinafter Frese) (of record).
The teachings of Lopez are discussed above. Lopez does not disclose wherein the biomolecule is gemcitabine and paclitaxel.
However, Frese discloses that a combination treatment of nab-paclitaxel and gemcitabine in a genetically engineered mouse model of pancreatic ductal adenocarcinoma increases intratumoral gemcitabine levels attributable to a marked decreased in the primary gemcitabine metabolizing enzyme, cytidine deaminase; paclitaxel reduced the levels of cytidine deaminase protein in cultured cells, resulting in the increased stabilization of gemcitabine [Abstract]. Frese further identifies that the combination treatment of paclitaxel and gemcitabine works synergistically [Discussion, pg. 266-267].
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Lopez discloses wherein the biomolecule may be pharmaceuticals. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated gemcitabine and paclitaxel as the biomolecule of Lopez since they are known and effective pharmaceuticals and the combination of paclitaxel and gemcitabine works synergistically for the treatment of pancreatic ductal adenocarcinoma as taught by Frese.
In regards to instant claim 35 reciting wherein the molecules comprise the gemcitabine and the paclitaxel at a predetermined dose or ratio, when the gemcitabine and paclitaxel are loaded in the mesoporous spaces of the mesoporous silica microspheres, the mesoporous silica microspheres would provide a predetermined dose and ratio of the gemcitabine and paclitaxel.
In regards to instant claims 32, 44 and 45, Frese teaches that the combination of gemcitabine and paclitaxel work synergistically to cause tumor regression and reduce metastasis [pg. 262, right column]. Provided this guidance by the prior art, a person having ordinary skill in the art would have been motivated to engage in routine experimentation to determine how much gemcitabine and paclitaxel to load into the pores of the mesoporous silica microspheres in order to achieve the optimal chemotherapeutic action for the treatment of pancreatic ductal adenocarcinoma.
In regards to instant claim 37 reciting wherein the submicron structure comprises a maximum dimension ranging from about 20 nm to about 300 nm, Lopez discloses wherein the microsphere may have a diameter of 10 nm. Therefore, a dimension not exceeding 20 nm would have been obvious.
In regards to instant claim 48 reciting removing the molecules that are not encapsuled, since Lopez discloses wherein unbound phospholipid and unsequestered dye are removed by repeated centrifugation and resuspension in buffer, it would have been obvious that any unbound components such as unbound molecules should and would be removed by repeated centrifugation and resuspension in buffer as well.
2. Claim 33 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lopez et al. (US 2004/0005352, Jan. 8, 2004) (hereinafter Lopez) (of record) in view of Frese et al. (Cancer Discovery, 2012) (hereinafter Frese) (of record), and further in view of Federico et al. (International Journal of Nanomedicine, Oct. 31, 2012) (hereinafter Federico).
The teachings of Lopez and Frese are discussed above. Lopez and Frese do not disclose wherein the gemcitabine comprises a gel-like precipitate.
However, Federico discloses wherein pretreatment with an ammonium sulfate solution gives rise to the appearance of a gel-like precipitate of the drug within the liposomes, a phenomenon specifically related to protonation of the amino group of gemcitabine (Figure 3). During experimentation, this approach allowed a drug-loading capacity of more than 90%, both for the precipitation of the drug as a salt sulfate in the aqueous liposomal compartment and for its considerable degree of interaction with phospholipids in the bilayers (page 5426, first paragraph of left column).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the gemcitabine to be a gel-like precipitate since this allows for a drug-loading capacity of more than 90% as taught by Federico.
3. Claim 47 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lopez et al. (US 2004/0005352, Jan. 8, 2004) (hereinafter Lopez ‘352) (of record) in view of Lopez et al. (US 7,514,267, Apr. 7, 2009) (hereinafter Lopez ‘267).
The teachings of Lopez ‘352 are discussed above. Lopez ‘352 does not disclose wherein the phospholipid bilayer comprises DOPC.
However, Lopez ‘267 discloses lipid bilayer coated beads (abstract). Phospholipids are often used to make lipid bilayers and can be used in the present supported lipid bilayers (col. 11, lines 65-67). Exemplary phospholipids include dioleoyl phosphatidylcholine (DOPC) (col. 12, line 38).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Lopez ‘352 discloses a phospholipid bilayer enveloping a mesoporous silica microsphere. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have enveloped the mesoporous silica microsphere of Lopez ‘352 with DOPC since it is a known and effective phospholipid as taught by Lopez ‘267.
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 17 and 30-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent Nos. 10,828,255; 10,143,660; 10, 765,636; 11,096,900; and 11,918,686. Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims recite a more specific version of the instant claims (i.e., the conflicting claims recite specific molecules) and thus read on the instant claims.
Claims 17 and 30-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 134, 139, 141, 142 and 155 of copending Application No. 17/384,214 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims recite a more specific version of the instant claims (i.e., the conflicting claims recite specific molecules) and thus read on the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 17 and 30-48 are rejected.
No claims are allowed.
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/TRACY LIU/Primary Examiner, Art Unit 1612