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 . Resonated
FINAL DETAILED ACTION
1. Applicant’s response filed on November 12, 2025 is acknowledged. Claims 1, 6-7, 18-19, and 22 have been amended. Claims 2-5, 11, 13-17, 20, and 23-25 have been canceled. Claims 26-29 have been added. Claims 1, 6-7, 18-19, 22, and 26-29 are currently pending and under examination.
Objections Withdrawn
2. In view of Applicant’s amendments the objection to claim 7, 18 and 22 for the cited informalities is withdrawn.
Rejections Withdrawn
3. In view of Applicant’s amendments, the rejection of claims 1, 5-7, and 18-19 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 by the use of parenthesis and by the use of the term “component”, “precipitation component”, and “derivatives” is withdrawn.
4. In view of Applicant’s amendments, the rejection of claims 1, 5-7, 18-20, and 22-23 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is withdrawn.
5. In view of Applicant’s amendments, the rejection of claim(s) 1, 5-7, 18-20 and 23 under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by O’Neill et al., WO 2013/153358 A1; Published: 10/17/13 is withdrawn.
New Grounds of Objection and Rejection Necessitated by Amendment
Claim Objections
6. Claim 7 is objected to because of the following informalities: Said claim depends upon a rejected based claim. Appropriate correction is required.
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.
7. Claim(s) 1, 18, 19, 22, 26 and 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over JP5730514B2; Published: 6/10/15, hereinafter JP’514.
Independent claim 1 is drawn to a method for treating a solid tumor in a subject in need thereof, comprising: locally administrating a combination of a yeast component as an active ingredient capable of providing a therapeutic effect and an agent to the subject, wherein said yeast component is selected from the group consisting of an inactivated yeast, a disrupted yeast, a disrupted yeast supernatant component, a yeast extract, a yeast ribonucleic acid and a yeast β-glucan, wherein said agent is selected from the group consisting of one or more of: an amino acid, a vital dye, and a cytotoxic agent, wherein said yeast component is administrated at a concentration of 0.25-25% in a solution, wherein said amino acid is administered at a concentration of 5-25% in a solution, wherein said vital dye is administrated at a concentration of 0.5-2.5% in a solution, and wherein said cytotoxic agent is administrated at a concentration of 0.1-15% in a solution, and wherein the therapeutic effect comprises a local treatment involving a local synergy or/and an immunotherapy.
Independent claim 18 is drawn to a method for treating a solid tumor in a subject in need thereof comprising: locally administering a therapeutically effective amount of a pharmaceutical composition comprising a yeast component capable of providing a therapeutic effect and an agent to the subject, wherein said yeast component is selected from the group consisting of an inactivated yeast, a disrupted yeast, a disrupted yeast supernatant component, a yeast extract, a yeast ribonucleic acid and a yeast β-glucan, wherein said agent is selected from the group consisting of one or more of: an amino acid, a vital dye and a cytotoxic agent, wherein said yeast component is administrated at a concentration of 0.25-25% in a solution, wherein said amino acid is administrated at a concentration of 5-25% in a solution, wherein said vital dye is administrated at a concentration of 0.5-2.5% in a solution, and where said cytotoxic agent is administrated at a concentration of 0.1-15% in a solution to an individual in need thereof within the solid tumor or/and outside the solid tumor, and wherein said locally administering outside a local lesion is conducive to producing a secondary immunological effect associated with a local synergy.
JP’514 teaches a method of administering a vaccine to an animal having or at risk of developing or alleviating cancer or a symptom of cancer, said vaccine includes a yeast vehicle and a fusion protein including a cancer antigen (see summary of the invention; page 3; meets claim 1 and 18). In certain embodiments, the animal has or is at risk of developing a cancer selected from the group comprising brain cancer, lung cancer, breast cancer, melanoma, and kidney cancer (see page 4; meets claim 22 and 26). The vaccine is administered by nasal administration and the animal has a brain tumor (see page 4; see claim 26).
JP’514 teaches that the method includes the following features regarding yeast media: the yeast medium is selected from the group comprising whole yeast, yeast spheroplasts, yeast cytoplasts, yeast forms, and yeast subcellular membrane extracts or fractions thereof. The yeast cell or yeast spheroplast used to prepare the yeast medium is transformed with a recombinant nucleic acid molecule encoding the antigen, so that the yeast cell or yeast spheroplast The antigen is expressed recombinantly. In this aspect, yeast cells or yeast spheroplasts that recombinantly express antigens are used to make yeast media comprising yeast cytoplasts, yeast forms, and yeast subcellular membrane extracts or fractions thereof. In one aspect of the invention, the yeast medium is derived from a non-pathogenic yeast (meets claim 6 and 19). In another embodiment, the yeast vehicle is Saccha.
In another embodiment, the yeast vehicle expresses a cancer antigen that is a fusion protein. The fusion protein comprises (a) at least one cancer antigen, and (b) a yeast protein bound to the N-terminus of the cancer antigen. The yeast protein is composed of about 2 to about 200 amino acids endogenous to the yeast protein (see page 5; meets claims 1 and 18). Further, a yeast selected from the group comprising the genus Romyce, Schizosaccharomyce, Kluberomyce, Hansenula, Candida, and Pichia. In one embodiment of the present invention, the genus Saccharomyces is S. cerevisiae (water-soluble β-glucan)(see page 6; meets claim 1, 6, 18 and 28). Said water-soluble β-glucan is of greater than 90% purity, absent evidence to the contrary.
Although various routes of immunization may be equally effective, it has been discovered that the yeast-based vaccine used in the present invention can stimulate effector cells that appear to be specific for the lung. Thus, other routes of administration are also effective, but as far as tested by administering the yeast vaccine through the respiratory tract (e.g. nasal administration, inhalation, intratracheal administration, etc.). It can provide an unexpectedly strong immune response and antitumor effect that cannot be achieved by other routes of administration (see page 15; meets claim 18). JP’514 teaches that the yeast vehicle may be formulated into the compositions of the invention, including formulations that are administered directly to the patient, or initially loaded into a carrier such as dendritic cells using techniques known to those skilled in the art. The yeast vehicle may be mixed with pharmaceutically acceptable excipients, such as isotonic buffers that are acceptable to the host cells. Examples of such excipients include water, saline, Ringer's solution, dextrose solution, Hank's solution (see page 17; meets claim 29) and adjuvants (see page 25).
In the present invention, an effective administration protocol (i.e., administering a vaccine or therapeutic composition in an effective manner) includes appropriate dose parameters and administration methods. Appropriate dose parameters and methods of administration are those that induce an immune response in an animal that has or is at risk of having a disease or condition and, as a result, preferably protects the animal from the disease. Effective dose parameters may be determined utilizing methods common in the art of specific diseases. Such methods include, for example, determining survival, side effects (i.e., toxicity), disease progression and regression. The effectiveness of the dose parameter of the therapeutic composition of the present invention in treating cancer is determined by evaluating the response rate. The above response rate means the proportion of patients who showed a response of partial or complete recovery among all patients. Recovery can be determined, for example, by measuring the size of the tumor or by microscopic examination for the presence of cancer cells in the tissue sample.
In the present invention, a suitable single dose is a dose that can elicit an antigen-specific immune response in an animal when administered one or more times over a suitable period of time. The dose will vary depending on the disease or condition being treated. For example, in the treatment of cancer, a suitable single dose may vary depending on whether the cancer being treated is a primary cancer or a metastatic cancer. One of ordinary skill in the art will be able to easily determine the dose to be administered at a time based on the size of the animal and the route of administration.
A suitable single dose of the therapeutic composition or vaccine of the present invention elicits an antigen-specific immune response when the therapeutic composition or vaccine is administered one or more times over a suitable period of time. Thus, a dose that can effectively provide yeast vehicle and antigen to cell types, tissues, or areas of a particular patient's body. For example, in certain embodiments, a single dose of the yeast vehicle of the present invention is about 1 × 1 per kilogram body weight of the organism to which the composition is administered (see page 26-27).
It would have been obvious before the effective filing date of the presently claimed invention to present their yeast component at a concentration of 0.25-25% in a solution; when present, to present their amino acid at a concentration of 5-25% in a solution; when present to present their vital dye at a concentration of 0.5-2.5% in a solution; and when present to present their cytotoxic agent at a concentration of 0.1-15% in a solution with a reasonable expectation of success. Limitations such as those recited in claims 1, 18 and 19 are being viewed as limitations of optimizing experimental parameters. Particularly, regarding the specific concentrations listed in the instant claims, MPEP 2144.05 states:
“Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).”
Accordingly, the subject matter of the rejected claims would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
8. Claim(s) 1 and 27 is rejected under 35 U.S.C. 103 as being unpatentable over JP5730514B2; Published: 6/10/15, hereinafter JP’514 as applied to claims 1, 18, 19, 22, 26 and 28-29 above, and further in view of Gruber et al., AU2009267052 B2 (WO 2010/1002937); Published: 01/07/10.
Independent claim 1 is drawn to a method for treating a solid tumor in a subject in need thereof, comprising: locally administrating a combination of a yeast component as an active ingredient capable of providing a therapeutic effect and an agent to the subject, wherein said yeast component is selected from the group consisting of an inactivated yeast, a disrupted yeast, a disrupted yeast supernatant component, a yeast extract, a yeast ribonucleic acid and a yeast β-glucan, wherein said agent is selected from the group consisting of one or more of: an amino acid, a vital dye, and a cytotoxic agent, wherein said yeast component is administrated at a concentration of 0.25-25% in a solution, wherein said amino acid is administered at a concentration of 5-25% in a solution, wherein said vital dye is administrated at a concentration of 0.5-2.5% in a solution, and wherein said cytotoxic agent is administrated at a concentration of 0.1-15% in a solution, and wherein the therapeutic effect comprises a local treatment involving a local synergy or/and an immunotherapy.
JP’514 teaches the limitations as set forth supra.
JP’514 does not specifically teach that their cytotoxic agent is 5-fluorouracil, as require by claim 27.
Gruber et al. teaches oral pharmaceutical compositions comprising 5-FC for the treatment of cancer. 5-FC is absorbed very rapidly and almost completely. Further, 5-FC rapidly clears the kidneys and is only minimally metabolized in the liver (see paragraphs 0041-42). The prodrug 5-FC is converted to a cytotoxic drug by the action of enzymes inherent in a microorganism; for example the yeast converts the pro-drug 5-FC into the cytotoxic chemotherapeutic agent 5-fluorouracil (5-FU) (see paragraph 0088).
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850,205 USPQ 1069, 1072 (CCPA 1980).
Lastly, all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. See the recent Board decision Ex parte Smith,--USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396). Thus it would have been obvious to combine 5-FC for the treatment of cancer because it is absorbed very rapidly (almost completely), it clears the kidneys and is only minimally metabolized in the liver; and yeast converts 5-FC into the cytotoxic chemotherapeutic agent 5-fluorouracil (5-FU) (see paragraph 0088).
Accordingly, the subject matter of the rejected claims would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
9. Claim(s) 1 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over JP5730514B2; Published: 6/10/15, hereinafter JP’514 as applied to claims 1, 18, 22, 26, 28, and 29 above, and further in view of Chengdu, CN108685944A; Published: 10/23/18.
Independent claim 1 is drawn to a method for treating a solid tumor in a subject in need thereof, comprising: locally administrating a combination of a yeast component as an active ingredient capable of providing a therapeutic effect and an agent to the subject, wherein said yeast component is selected from the group consisting of an inactivated yeast, a disrupted yeast, a disrupted yeast supernatant component, a yeast extract, a yeast ribonucleic acid and a yeast β-glucan, wherein said agent is selected from the group consisting of one or more of: an amino acid, a vital dye, and a cytotoxic agent, wherein said yeast component is administrated at a concentration of 0.25-25% in a solution, wherein said amino acid is administered at a concentration of 5-25% in a solution, wherein said vital dye is administrated at a concentration of 0.5-2.5% in a solution, and wherein said cytotoxic agent is administrated at a concentration of 0.1-15% in a solution, and wherein the therapeutic effect comprises a local treatment involving a local synergy or/and an immunotherapy.
JP’514 teaches the limitations as set forth supra.
JP’514 does not specifically teach the use of a vital dye, as require by claim 27.
Chengdu teaches methods and compositions comprising a vital stain for local administration for the prevention and treatment of mammalian solid tumors. Said composition may comprise one or more pharmaceutically acceptable excipients (see abstract). The present invention has the following advantages compared with existing antitumor technology: demonstrates that unusual superelevation validity while not comprising the safety of reduction and with existing vital stain light power technology it shows efficiently. Additionally, Chengdu produces additional collaboration by the introduction of the drug of different pharmacology to further increase safety and the validity for the treatment thereof. Further, the composition preparation is convenient, the cost is cheap and thus many people are helped with the difficult to bear high cost while enjoying effective treatment (see page 5).
It would have been obvious before the effective filing date of the presently claimed invention to incorporate a vital stain to the composition and method of Chengdu because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. See the recent Board decision Ex parte Smith,--USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396). Thus it would have been obvious to combine said vital stain because a vital stain is known to be used for local administration for the treatment of mammalian solid tumors, it encompasses advantages to include superelevation validity while not comprising the safety of reduction and produces additional collaboration by the introduction of the drug of different pharmacology to further increase safety and the validity for the treatment thereof. Lastly, because said stain is convenient, the cost is cheap and many people are helped with the difficult to bear high cost while enjoying effective treatment.
Accordingly, the subject matter of the rejected claims would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
10. No claim is allowed.
11. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKIA J JACKSON-TONGUE whose telephone number is (571)272-2921. The examiner can normally be reached Monday-Friday 930AM-530PM.
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/LAKIA J JACKSON-TONGUE/Examiner, Art Unit 1645 February 6, 2026
/BRIAN GANGLE/Primary Examiner, Art Unit 1645