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 .
Priority
The present application is a National Stage entry of International application PCT/EP2023/067195 filed 06/23/2023, which claims the benefit of Provisional US application 63357757 filed 07/01/2022.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 12/31/2024, in the matter of Application N° 18/880,336. Said documents have been entered on the record. The Examiner further acknowledges the following:
Claims 1-13 and 17-22 are pending.
Claims 1-13 and 17-22 are presented for examination and rejected as set forth below.
Claim Objections
Claims 1-3 17 are objected to because of the following informalities: the orellanine term is capitalized in the claim set, implying that orellanine is a product name, when it refers to the generic name of the molecule. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-13 and 21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature or natural phenomenon without significantly more.
Claims 1-13 and 21 simply recite orellanine formulations at different concentrations and/or pH. Dinis (Human and Experimental Toxicology, 2016) teaches orellanine to be a toxin produced by mushroom species (abstract), that has a specific solubility profile according to pH environment, that is inherent to the molecule itself (Figure 1, Table 1, pg 1019-1020). Therefore, the instant claims recite a product of nature. There is no evidence within the specification that the compositions recited in claims 1-13 and 21 contain markedly different characteristics from their naturally-occurring counterparts, because pH itself does not change the solubility of orellanine itself, because the solubility of a molecule in a certain carrier is inherent to the free base and/or salt form (whereby the free base and salt forms of orellanine are present in natural organisms).
The method claims 17-20 and 22 are excluded from this product of nature rejection, because they are method claims; however, they are objected to for depending from claim 1, that is rejected herein.
This judicial exception is not integrated into a practical application because the instantly amended claims do not introduce any additional limitations which transform or improve on the judicial exceptions recited in claims 1-13 and 21 and do not do anything beyond generally linking the use of the judicial exception to a particular technological environment.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because compositions comprising the instantly claimed ingredients as pharmaceutical compositions, are well-understood as possessing routine, and conventional activity. Haraldsson (US20100152243A1) teaches formulations of orellanine in buffers [0085] and varied active ingredient concentrations [0078-0079, 0091] relevant for renal cancer treatment (abstract/claims). Claims 1-13 and 21 are directed to a judicial exception and do not qualify as eligible subject matter under 35 U.S.C. §101.
Claim Rejections - 35 USC § 112
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.
Claim 17 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 exemplary language (“e.g.”), which is indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP 2173.05(d). Furthermore, the claim recites a genus followed by a species. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For examination purposes, the broadest range is used. For examination purposes, the examples provided by the exemplary language are not considered limitations of the claim, and the broadest reasonable interpretation is used.
Claim Rejections - 35 USC § 103
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.
Claims 1-13 and 17-22 are rejected under 35 U.S.C. 103 as being unpatentable over Haraldsson (US20100152243A1; IDS filed 12/31/2024 recites the family member WO2010040750), and in further view of Annis (US20160101145A1) and Dinis (Human and Experimental Toxicology, 2016).
Applicant’s claims are directed to a pharmaceutical aqueous solution formulation comprising from 0.1 to 40 mg/ml of orellanine; and a buffer; wherein the pH of the formulation is in the range of 7 to 8. Claims 17-22 further describe method and kit claims. Note that any “optional” element is not a required limitation of the claim set.
Haraldsson teaches orellanine intravenous injection formulations, which are useful for the treatment of renal cancer (abstract, Haraldsson – claim 14), including methods and kits (Haraldsson – claims 1 and 19-20).
Regarding claims 1-3: Haraldsson teaches a range of 0.1 to 25 mg/mL intravenous injection formulation (overlaps and/or reads on 0.1 to 40 mg/mL of instant claim 1) [0077-0078], which optionally comprises one or more pharmaceutically acceptable additives [0078]. With regard to the numerical range, a prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art (see 2144.05(I)). See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.”).
Regarding general solubility, Haraldsson teaches the parenteral formulations are solutions (i.e., that infers clear, homogeneous, transparent) [0086]. Furthermore, Haraldsson teaches that the active is administered in “a water-soluble form, e.g., as a pharmaceutically acceptable salt of an organic or inorganic acid, e.g., hydrochloride, sulfate, hemi-sulfate, phosphate, nitrate, acetate, oxalate, citrate, maleate, mesylate, etc.” [0084] such that it is known in the art that salt forms of organic molecules affect solubility. Haraldsson also teaches incorporation of buffers [0085], whereby formulation buffers have the effect of modulating formulation pH and also affects the general solubility of formulation components in the carrier. Furthermore, certain preferred compounds suitable for use in the methods of the invention are “sufficiently water-soluble in neutral form in such a way that they may be delivered without pre-generation of a pharmaceutically acceptable salt” [0084].
Regarding claim 12: Haraldsson teaches physiological saline solution (i.e., aqueous NaCl) for injection [0112-0115].
Regarding claims 17-18: Haraldsson teaches a method of making by mixing ingredients (i.e., including buffers [0085]), according to conventional protocols [0085-0088], where the order and amount of mixing is not critical [0085-0088].
Regarding claim 19-20 and 22: Haraldsson teaches a method of intravenous [0077-0078] treatment for a cancer patient (Haraldsson – claim 1), including a dose of 1 mg/kg and about 20 mg/kg of the compound (Haraldsson – claim 7), daily (Haraldsson – claims 11-13) and between two and seven days apart (Haraldsson – claims 8-10).
Regarding claims 21: Haraldsson teaches a kit for treatment (Haraldsson – claims 19-20)
In summary, Haraldsson orellanine intravenous formulations of 0.1 to 25 mg/mL for renal cancer treatment. However, Haraldsson does not teach the pH of the formulation range (instant claim 1 and 4-5), buffer concentration (instant claims 6-7), the specific phosphate buffer (instant claim 8-9). or the osmolality values (instant claims 10-11), and the sodium chloride amount (instant claims 13).
Annis teaches intravenous active agent formulations [0094] for renal cancer [0087]. Annis teaches buffering agents such as phosphate-citrate buffer or sodium phosphate (reads on instant claims 8-9) [0024], in the amount of 0.001-10 w/v% (Annis – claim 304-305) (encompassing and/or reading on the 40-60 mM amount of instant claims 6-7, because, for example, 50 mM of sodium phosphate dibasic = 7.1 g/L = 7.1 g/1000 mL = 0.71 w/v%), and in pHs of 7-8 (reads on pH range of instant claims 1 and 4-5 by encompassing those ranges) [0172]. With regard to the numerical range, note that "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003) (see 2144.05(I)).
Annis also teaches tonicity adjusting agent is sodium chloride [0190] in 1-10 w/v% (overlaps with the instant range of instant claim 13) (Annis – claim 300), that can further be optimized [0190], to achieve osmolarity values of 300 mOsM (reads on mOsm values of instant claims 10-11) [0189]. Annis teaches that the above ingredients and values are used for suitable intravenous injection formulations for cancer treatment (abstract, [0171, 0175, 0183, 0212, 0505]), and furthermore, the buffering agent can be used to control pH of the formulation and/or to maintain stability of the drug [0184], and the tonicity/osmolarity of the aqueous pharmaceutical formulations can be adjusted to be isotonic with human plasma, in order to avoid damage to the tissues [0189]. Furthermore, Annis teaches the formulated aqueous pharmaceutical compositions provide increased solubility of the drugs compared to the solubility of the drugs in water alone [0179].
Dinis teaches orellanine is soluble in dilute sodium hydroxide, ammonium hydroxide, and dimethyl sulfoxide; slightly soluble in methanol; and practically insoluble in most organic solvents and water (pg 1019-1020). Dinis teaches orellanine is also well soluble in alkaline solutions (reads on pH 7-8, because anything above pH 7 is considered basic) (pg 1019-1020). Thus, because the basic range of a solution is >7 pH, then the instant pH range of 7-8 overlaps with this range. With regard to the numerical range, a prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art (see 2144.05(I)). See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.”).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the disclosure of Haraldsson to optimize the pH (via phosphate buffer) and osmolarity (via tonicity agent of NaCl) of the intravenous injection formulations of Annis, because Annis teaches the well-known benefits derived from optimizing tonicity/osmolarity and pH, regarding the active drug agent and the overall performance of the formulation [0184, 0189], that are standard optimization considerations in pharmaceutical drug development programs.
Furthermore, Dinis teaches that bases (i.e., this effectively changes the final pH of the solution, where pH is further modifiable by acids and/or buffers) can be incorporated to modify the solubility of orellanine in solution. Thus, the claim scope, as a whole, appears to represent standard formulation optimization in comparison to the combined Prior Art, with the added knowledge that orellanine demonstrates improved solubility transitioning from acidic/neutral conditions to basic conditions as shown by Dinis (pg 1019-1020), whereby 0.1 to 25 mg/mL formulations, as solutions for intravenous injection formulations for cancer treatment, have already been demonstrated by Haraldsson in practice [0077-0078, 0086].
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 1-13 and 17-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over, and in further view of Haraldsson (US20100152243A1), Annis (US20160101145A1) and Dinis (Human and Experimental Toxicology, 2016):
claims 1-14 of Patent No. US8053430B2
Although the claims at issue are not identical, they are not patentably distinct from each other, because both claim sets teach orellanine intravenous formulations. The claims scopes differ, because the instant claims teach a more narrowly limited formulation in comparison to the compositions of ‘430 (i.e., namely, pH).
This is remedied by the combined Prior Art, which teaches additional elements common to intravenous formulations (as discussed in the 103 rejection above). One of ordinary skill in the art would have been motivated to modify the teachings of ‘430 with the additives and/or optimized property limitations of intravenous formulations, which are useful for cancer treatment, as taught by the combined Prior Art, because this represents a typical developmental process of transforming a bioactive molecule into a relevant pharmaceutical product for clinical treatment, as demonstrated by the Prior Art.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAJAN PRAGANI whose telephone number is (703)756-5319. The examiner can normally be reached 7a-5p EST (M-Th).
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/R.P./Examiner, Art Unit 1614 8/6/2026
/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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