DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is the first Office action on the merits of the claims.
All citations to the Manual of Patent Examining Procedure (MPEP) refer to Revision 01.2024, which was released in November 2024.
Status of the Claims
In the Preliminary Amendment filed 12 February 2024, Applicant amended claims 1-5, 7-13, 18-19, and 28; cancelled claims 6, 14-17, 20-27, and 29-37; and added five new claims, i.e., claims 38-42. Accordingly, claims 1-5, 7-13, 18-19, 28, and 38-42 are pending.
Claim Objections
Claims 1-5, 7-13, 18-19, 28 and 38-42 are objected to because of the following minor informality: In claim 1, the word “yeasts” in the phrase “obtaining autolyzed yeasts cells” should be singular. Appropriate corrected is required.
Claim Rejections - 35 U.S.C. 112(b)
The following is a quotation of 35 U.S.C. 112(b):
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.
Claims 1-5, 7-13, 18-19, 28, and 38-42 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter that the inventor regards as the invention.
Regarding claim 1, the phrase “namely peptide contaminants” leads to confusion over the intended scope of the claim. Is the claim language merely exemplary and, therefore, not further limiting? MPEP § 2173.05(d) (“If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph should be made.”).
In further regard to claim 1, the phrase “suitable detergents” is unclear. What distinguishes a suitable detergent from a detergent that is not suitable? The specification does not provide guidance on the genus of suitable detergents. MPEP § 2173.04 (“a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim)”).
Regarding claim 2, the phrase “before purifying the deproteinized glucan extract” is unclear. Does the claim actually require an (additional) step of purifying the spray-dried deproteinized extract?
Regarding claims 5, 10 and 38-39, the limitations recited in these claims do not appear to be directed to additional active (manipulative) steps. Rather, they are refinements concerning the “extract” step of claim 1. Hence, there is an insufficient nexus between the limitations introduced in claims 5, 10 and 38-39, respectively, and claim 1.
In further regard to claims 10 and 39, there is no antecedent basis for the following limitation: “the obtained solid glucan extract.” Applicant is referred to MPEP § 2173.05(e) (lack of antecedent basis).
Regarding claim 12, the following two trademarks or tradenames are recited therein: “Tween 20” and “Triton.” A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. The trademarks/tradenames recited in claim 12 are used to identify or describe detergents and, consequently, cause confusion as to the scope of the claim. Therefore, claim 12 does not comply with the requirements of 35 U.S.C. 112(b). MPEP § 2173.05(u). Applicant is required to delete the trademarks/tradenames and, if desired, replace them with generic terminology describing the corresponding detergent.
Regarding claims 41-42, the preamble of both these dependent claims is inconsistent with claim 1, which is directed to a method of making, not to extracted glucans. The examiner recommends clarifying claims 41 and 42 by adopting the preamble of claim 13.
Claim Rejections - 35 U.S.C. 112(d)
The following is a quotation of 35 U.S.C. 112(d):
[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 19 is rejected under 35 U.S.C. 112(d) as being of improper dependent form.
Claim 19 recites as follows: “The pharmaceutical composition according to claim 18, wherein the composition is administrated as a nasal spray or as an intravenous preparation.” Thus, the limitation introduced in claim 19 is an active (manipulative) step relevant to a method of treatment. Claim 18, however, is directed to a pharmaceutical composition. Consequently, claim 19 does not actually further limit claim 18 and, therefore, fails to comply with 35 U.S.C. 112(d).
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
Claim Rejections - 35 U.S.C. 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 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.
Claims 1-5, 7-13, 18, and 38-42 are rejected under 35 U.S.C. 103 as being unpatentable over Muller (“The application of various protic acids in the extraction of (1→3)-β-d-glucan from Saccharomyces cerevisiae.” Carbohydrate research 299.3 (1997): 203-208) in view of Avramia (“Spent Brewer’s yeast as a source of insoluble β-glucans.” Int’l Journal of Molecular Sciences 22.2 (2021 January): 825), Liepens (“Drying enhances immunoactivity of spent brewer’s yeast cell wall β-d-glucans.” Journal of Biotechnology 206 (2015): 12-16), and Cassone (WO 94/03500 A1).
Muller is directed to the application of various protic acids in the extraction of (1→3)-β-d-glucan from the yeast Saccharomyces cerevisiae.
Muller discloses that the water-insoluble (1→3)-β-d-glucan is isolated as follows: “Briefly, four batches of S. cerevisiae (454 g) were extracted (3×) with 0.75 M NaOH at 100 °C. The residue was then sequentially extracted with 2.5 N, 1.75 N and 0.94 N hydrochloric, acetic, formic or phosphoric acid at 100 °C. The residue was then extracted with boiling 1% acidic ethanol (6×), followed by boiling 1% alkaline ethanol (1×). The acid ethanol was prepared with the corresponding acid. The remaining residue was washed in 18 mΩ water at 100 °C (3×), allowed to sediment, harvested and lyophilized to dryness. The yield was 3-5%.” Page 207.
However, Muller is silent as to whether (i) the cells of S. cerevisiae were autolyzed and (ii) the glucan yielded by the isolation process was washed or otherwise treated with a detergent to remove protein contaminants. Consequently, Muller does not satisfy claim 1 of the present application. As explained below, the following three references compensate for the deficiencies in Muller: Avramia, Liepens, and Cassone.
Avramia is directed to Saccharomyces cerevisiae (brewer’s yeast) as a source of insoluble β-glucans. Title/Abstract and page 2.
Avramia teaches: “Currently, a number of methods to improve the process of cell lysis to allow the release of cytoplasmic contents exists. From the chemical, physical or enzymatic among the most accessible methods in the extraction of glucans are milling with glass beads in diameters of 0.25–1 mm, induced autolysis at 55 °C, cell rupture with enzymes….” Page 9 (emphasis added).
Avramia teaches: “One of the most commonly used methods that cause the death of a yeast cell is the process of cell destruction by its own enzymatic mechanisms. Autolysis is a form of enzymatically cellular death that takes place under the action of its own enzymes, in which the cell wall is partially destroyed allowing the cytoplasm to evacuate outside the cell. Defined as the hydrolysis of intracellular polymers under the action of hydrolytic enzymes associated with cell death, induced autolysis occurs at temperatures between 50–55 C within several hours, or it may be due to senescence after serial replications during fermentation.” Page 10 (emphasis added).
Liepens is directed to immunogenic (1→3)-β-d-glucans from brewer’s yeast. Page 12.
Liepens teaches that the yeast biomass was subjected to autolysis prior to the sequence of alkaline treatment (with NaOH) and acid treatment (with HCl), thereby establishing compatability. Page 13 at Section 2.3.
Cassone is directed to glucans with immunostimulant activity, to a process for their preparation, and to pharmaceutical compositions containing them. Abstract.
Cassone teaches that the glucan can be obtained from Saccharomyces, among other yeasts. Page 3, lines 6-10; see also page 17 at claim 3.
Cassone teaches that the “treatment of the extract with detergent at high temperature,” referred to therein as Step (d), “contributes to the peculiar characteristics of the glucans of the invention,” which are “high immunostimulant activity, higher than that of known glucans, low toxicity and immunogenic activity.” Page 3 at lines 19-27 (emphasis added).
Cassone teaches: “In order to assure an optimal removal of all the protein components which may be dangerous for the therapeutic use, the obtained glucan is further purified by treatment (1-2% w/v suspension) with a 2% sodium dodecylsulfate solution in Tris EDTA mercaptoethanol for 1,5 hours at the boiling temperature.” (Emphasis added) Page 6, lines 6-12.
Before the effective filing date of the claimed invention, the teachings of Avramia, Liepens, and Cassone would have motivated a person having ordinary skill in the art to modify Muller by autolyzing the yeast cells (one of the most commonly used methods for causing the death of yeast cells) and washing the second residue (analogous to Applicant’s second pellet) with a sodium dodecylsulfate solution (detergent) to render the extracted glucans safer for therapeutic applications by removing protein contaminants and, potentially, enhance their immunogenic activity. It is worth noting that the intended result recited in claim 1 (i.e., a limit of 0.1 wt% peptide contaminants) is not afforded patentable weight because it does not result in a manipulative difference over the combination of prior art references (Muller in view of Avramia, Liepens, and Cassone), as applied above. MPEP § 2111.04(I) (a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited’”), quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003)). Therefore, claims 1, 4, 7-8, 11-12, and 40 are prima facie obvious.
Regarding claims 2 and 3, Liepens teaches that “[d]rying in combination with carboxylmethylation (CM), endows spent brewer’s yeast β-d-glucans with the immunoactivity similar or exceeding that of a well-characterized fungal BRM pleuran.” Abstract (emphasis added); see also page 13 (“Chemical modification (phosphorylation or carboxylation) of glucose moieties at O-2 or O-6 positions leads to solubilization of the (1→3)-β-d-glucan). Figure 4 of Avramia teaches there are three ways to dry the glucan extract, one of which is spray-drying. Page 14. Avramia additionally teaches that “spray-dried β-glucans show a significantly higher immune response on the immune system than those dried by lyophilization or after washing with ethanol and air dried.” Page 16 (emphasis added).
Regarding claims 5, 10 and 38-39, Applicant is alerted that “‘[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.’” MPEP § 2144.05(II)(A), quoting In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Regarding claim 9, Liepens teaches washing the sediment (pellet) twice with distilled water immediately after the initial alkaline treatment (NaOH). Page 13 at Section 2.3; see also Cassone at page 9, lines 10-15.
Regarding claims 13 and 41-42, it is important to acknowledge that Cassone discloses that treatment with the detergent assists in purifying the glucan extract by optimally removing all the protein contaminants. Pages 3 and 6. That teaching provides a sound basis for the examiner’s position that the concentration limits on peptide contaminants recited respectively in claims 13 and 41-42 are satisfied. MPEP § 2112.01(I) (“‘When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.’”), quoting In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Regarding claim 18, Cassone teaches pharmaceutical compositions comprising immunostimulant glucans. Page 1, lines 1-3; page 16, lines 8-11; page 18 at claim 8.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Muller in view of Avramia, Liepens, and Cassone, as applied above to claims 1-5, 7-13, 18 and 38-42, and further in view of Liu (“Aluminum hydroxide colloid vaccine encapsulated in yeast shells with enhanced humoral and cellular immune responses.” Biomaterials 167 (2018): 32-43).
Although Muller (as modified above by Avramia, Liepens, and Cassone) teaches pharmaceutical compositions comprising immunostimulatory β-glucans, that combination is silent as to whether the pharmaceutical composition can further comprise aluminum salts or squalene and, consequently, does not satisfy claim 28. As explained below, Liu compensates for this deficiency.
Liu teaches: “Aluminum salt (Alum) is one of the most important immune adjuvants approved for use in humans, however it is not suitable for vaccination against various chronic infectious diseases and cancers for not being able to induce cell-mediated (Th1) immunity.” Abstract.
Liu teaches: “β-Glucan particles (GPs) are a type of natural particles derived from the yeast glucan shells, with a very uniform particle size of 2-4 mm.” Page 33, right column. “Moreover, GPs are a very strong Th1-biased immunostimulant, as the β-glucans on its surface can act as a PAMP and deliver ‘danger’ signals to DCs, resulting in strong DC activation and high expression of the co-stimulatory molecules CD40, CD80 and CD86.” Id.
Liu teaches: “As Alum has been proven to be a safe adjuvant inducing strong humoral responses, and β-glucans are safe for human utilization with high APC targeting and induce strong Th1-biased cellular response, the combination of Alum adjuvant with β-glucan particles may be an ideal vaccine delivery system.” Page 33, right column (emphasis added).
Before the effective filing date of the claimed invention, the teachings of Liu would have motivated a person having ordinary skill in the art to modify Muller (in view of Avramia, Liepens, and Cassone) by including alum in the β-glucan formulation, in an effort to enhance the formulation’s immunogenic activity by adding the capability of inducing humoral responses. Therefore, claim 28 is prima facie obvious.
Claim Rejections - Double Patenting (Non-Statutory)
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 obviousness-type 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR1.321(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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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 eTerminalDisclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/ eTD-info-I.jsp.
Claims 1-5, 7-13, 18-19, 28, and 38-42 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 18 of co-pending Application No. 18/253,484 (as preliminarily amended on 01 December 2025) in view of Cassone (WO 94/03500 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: Conflicting claim 18 of the ’484 Application is directed to “[a] method of obtaining a yeast β-Glucan comprising: obtaining autolyzed yeasts cells; extract dried alkali-glucans of the yeast by adding an alkaline solution to the yeast cells in a solid-liquid extraction and collecting a first pellet; and adding to the obtained first pellet an alcoholic solution and an acid solution in a second solid-liquid extraction to obtain a second pellet with yeast β-Glucan.” However, conflicting claim 18 is silent regarding the addition of a detergent to the second pellet and, therefore, does not satisfy claim 1 of the present application. Cassone teaches: “In order to assure an optimal removal of all the protein components which may be dangerous for the therapeutic use, the obtained glucan is further purified by treatment (1-2% w/v suspension) with a 2% sodium dodecylsulfate solution in Tris EDTA mercaptoethanol for 1,5 hours at the boiling temperature.” (Emphasis added) Page 6, lines 6-12. The foregoing teaching of Cassone would have motivated a person having ordinary skill in the art to modify conflicting claim 18 by washing the second pellet with a sodium dodecylsulfate solution (detergent) to render the pelleted glucans safer for therapeutic applications. Therefore, the present claims are not patentably distinguishable over conflicting claim 18.
This is a provisional rejection because the conflicting claim has not been patented.
Conclusion
Claims 1-5, 7-13, 18-19, 28, and 38-42 are rejected.
Claims 1-5, 7-13, 18-19, 28 and 38-42 are also objected to.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER ANTHOPOLOS whose telephone number is 571-270-5989. The examiner can normally be reached on Monday – Friday (9:00 am – 5:00 pm). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany P. Barham, can be reached on Monday – Friday (9:00 am – 5:00 pm) at 571-272-6175. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.A./
07 March 2026
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611