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
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in the instant application on 03/02/2023.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/20/2026 has been entered.
Response to Amendment
Applicant's amendment and argument filed 04/20/2026 in response to the final rejection, are acknowledged and have been fully considered. Any previous rejection or objection not mentioned herein is withdrawn.
Claims 1-2, 5, 8-11 and 25-37 are pending.
Election/Restrictions
Newly submitted claims 32-37 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: The applicant has added new claims directed to a distinct product and the original examination was to a method of prevention and treatment of a bone-related disorder.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 32-37 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 1-2, 5, 8-11 and 25-31 are being examined on the merits.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 5 and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Hii Eiichi et. al. (JP2019048803A) and Maria-Bernadette Madel (from IDS, “Abstracts of the ECTS Congress 2018 P062 Implication of microbiota in the emergence of inflammatory osteoclasts: protective effect of Saccharomyces boulardii CNCM I-745” Calcified Tissue International vol. 102, No. S1, 1 May 2018, pages S31-S32). This rejection is maintained due the arguments filed 04/20/2026.
Eiichi’s general disclosure is about bone formation promoters (see abstract).
Regarding claims 1-2, 5, Eiichi discloses a composition for promoting bone formation, suppressing bone resorption, improving bone remodeling, suppressing osteoclast activity, enhancing osteoblast activity, comprising a polyamine-containing yeast as an active ingredient (see claims 1-8).
Eiichi teaches “as used herein, “promoting bone formation” refers to promoting bone formation by osteoblasts, and preferably refers to promoting bone formation by enhancing osteoblast activity. In the present specification, "osteoblast activity" preferably refers to cell proliferation ability and cell differentiation ability. More preferably, "promoting bone formation" in the present specification refers to promotion of proliferation and maturation of osteoblasts, or promotion of bone formation thereby” (see last para. page 2). This would indicate osteoblastogenesis as instantly claimed.
Eiichi discloses wherein the yeast is Saccharomyces (see product example 1, page 9, bottom of page 6). Eiichi discloses wherein the composition is for treating osteoporosis (see claim 5).
Regarding claims 1 and 9, Eiichi discloses administering the composition orally and in effective amounts (see 2nd last para. of page 2, last 3 paras of page 9).
Regarding claim 8, Eiichi discloses wherein the yeast are lyophilized (see page 6, para. 7).
Regarding claims 10-11, Eiichi teaches drugs such as active vitamin D3 and bisphosphonates have been used to treat osteoporosis (see description first para.).
Eiichi discloses a method for promoting osteoblastogenesis in an individual comprising administering to the individual an effective amount of a yeast cell derived product, however does not teach the Saccharomyces species as Saccharomyces boulardii.
Madel teaches that Saccharomyces boulardii CNCM-I-745, a yeast probiotic has protective effects on bone destruction and osteoporosis and that the conditioned media inhibits osteoclastogenesis in vitro without affecting cell viability. The results demonstrate that specific i-OCL inhibition is highly promising to combat inflammatory bone destruction. There is a protective effect of Saccharomyces boulardii CNCM I-745 on bone destruction the research provides a novel regulatory mechanisms as new therapeutic targets for inflammatory bone loss (see abstract and fig 1).
Therefore it would have been obvious to persons having skill in the art before the effective filing date to use Saccharomyces boulardii and/or the conditioned media in the composition taught by Eiichi, because this species of Saccharomyces is known to have protective effects on bone destruction and osteoporosis. Additionally, the conditioned media inhibits osteoclastogenesis in vitro without affecting cell viability. The results demonstrate that specific i-OCL inhibition is highly promising to combat inflammatory bone destruction. Thus, selection of the species is prima facie obvious to include in a method of treatment of a bone-related disorder. Including both species in the composition would create a composition which would guarantee both bone promoting properties and for inhibiting inflammatory bone destruction and would create a more comprehensive treatment for individuals with osteoporosis, osteopenia, fracture and osteomalacia.
Claims 25-31 are rejected under 35 U.S.C. 103 as being unpatentable over over Hii Eiichi et. al. (JP2019048803A) and Margret Moré and Yvan Vandenplas (Saccharomyces boulardii CNCM I-745 Improves Intestinal Enzyme Function: A Trophic Effects Review, Clinical Medicine Insights: Gastroenterology Volume 11: 1-14, December 17, 2017). This is a new rejection based on the amendments filed on 04/20/2026.
Eiichi teaches a composition for promoting bone formation, suppressing bone resorption, improving bone remodeling, suppressing osteoclast activity, enhancing osteoblast activity, comprising a polyamine-containing yeast as an active ingredient (see claims 1-8). Eiichi also teaches wherein the composition should contain the polyamines putrescine, spermidine and spermine (see claim 11). Eiichi discloses wherein the yeast is Saccharomyces (see product example 1, page 9, bottom of page 6). Eiichi discloses wherein the composition is for treating osteoporosis (see claim 5).
“There are mainly three types of polyamines in the human body, which are putrescine, spermidine and spermine, and the amount thereof decreases from the age of 20 years. Polyamines are components necessary for cell division, and it is thought that when the amount of intracellular polyamines decreases, the turnover of cells is reduced and senescence is promoted. Patent Document 1 and Non-patent Document 1 disclose that spermine and spermidine have an inhibitory effect on osteoclast differentiation and / or osteoclast proliferation. Further, Patent Document 1 discloses a preventive and / or therapeutic agent for a disease involving differentiation to osteoclasts and / or proliferation of osteoclasts, which contains spermine or spermidine as an active ingredient. However, in order to restore the decreased bone mass in osteoporosis patients etc., it is not always enough to suppress the activity of osteoclasts alone” (see para. 3, page 5).
Eiichi teaches as a means to modify yeast so as to contain large amount of polyamine, for example, a method of culturing yeast in medium containing a predetermined concentration of polyamine (see last para. of page 6, first para. of page 7).
Eiichi teaches “The polyamine-containing yeast in the culture is preferably used in the present invention after being separated from the culture medium or other contaminants by a method such as filtration or sieving. The polyamine-containing yeast described above has an action of activating osteoblasts, more specifically, an action of proliferating and maturing osteoblasts, and promotes bone mineralization. Therefore, the polyamine-containing yeast is effective in promoting bone formation” (see page 7, para. 4-5).
Eiichi teaches “as used herein, “promoting bone formation” refers to promoting bone formation by osteoblasts, and preferably refers to promoting bone formation by enhancing osteoblast activity. In the present specification, "osteoblast activity" preferably refers to cell proliferation ability and cell differentiation ability. More preferably, "promoting bone formation" in the present specification refers to promotion of proliferation and maturation of osteoblasts, or promotion of bone formation thereby” (see last para. page 2). This would indicate osteoblastogenesis as instantly claimed.
Eiichi discloses administering the composition orally and in effective amounts (see 2nd last para. of page 2, last 3 paras of page 9). Eiichi teaches wherein the individual treated was seven-week-old female mice and this teaches administering to a female.
Eiichi discloses a method for promoting osteoblastogenesis in an individual comprising administering to the individual an effective amount of a yeast cell conditioned medium, however does not teach the Saccharomyces species as Saccharomyces boulardii.
Moré teaches that Saccharomyces boulardii CNCM I-745 5 synthesizes and secretes polyamines (see abstract), and teaches Lyophilized S. boulardii CNCM I-745 contains a measurable content of the biogenic polyamines spermine, spermidine, and putrescine (see right column, 2nd para., page 4), and that the yeast provides increased levels of polyamines, which are taken up by the polyamine transport system and/or function as signaling molecules (see Figure 1, page 5).
Therefore it would have been obvious to persons having ordinary skill in the art before the effective filing date to use Saccharomyces boulardii CNCM I-745 in the invention taught by Eiichi for a method of promoting osetoblastogenesis in an individual having a bone-related disorder because as Moré teaches that Saccharomyces boulardii CNCM I-745 synthesizes and secretes polyamines, specifically the polyamines spermine, spermidine, and putrescine, which are the polyamines from the same bacteria genus known for having bone promoting osteoblastogenic activities. Eiichi teaches that Saccharomyces species containing these polyamines are useful in promoting bone formation and Moré teaches that Saccharomyces boulardii CNCM I-745 indeed synthesize and secretes these polyamines in measurable amounts. Optimizing the amount of polyamines to be at the effective amount would have been prima facie obvious.
It would have been obvious to optimize the dose being administered to be that of the instantly claimed range because the art already teaches the composition to have the same activity and determining the particular effective dose is well within the purview of any skilled artisan especially given the prior art. Administering the composition to individuals older than 45, 55, 65 or 80 is also prima facie obvious as these would be parameters (age) of different patients that would benefit from such a treatment.
There would have been a reasonable expectation of success in selecting this particular species (strain) and expecting the composition to have the same activity such as osetoblastogenesis activity as persons having ordinary skill in the art could increase/optimize the amount of polyamines collected in the conditioned medium and without any undue experimentation.
Response to Arguments
Applicant's arguments filed 04/20/2026 have been fully considered but they are not persuasive. The declaration under 37 CFR 1.132 filed 04/20/2026 is insufficient to overcome the rejection of claims based upon 103 as set forth in the last Office action because: Dr. Bernard states that the teachings of Eiichi, cannot be reasonably extrapolated to a different strain of yeast with a lower polyamine content. Dr. Bernard makes this assumption without supported evidence. The Office brings in new art to show that the same strain of S. boulardii indeed secrete the same polyamines in measurable amounts and therefore it would have been obvious to select this strain in light of the Eiichi’s teachings. Dr. Bernard states that the claimed strain of yeast has lower polyamine content than that of the Eiichi’s art however does not supply any evidence that this is true. Dr. Bernard argues that bone formation and bone destruction do not always happen in tandem and that using the species taught by Eiichi would not bring about the instantly claimed effects. The Office brings in new art from Moré to teach why it would have been obvious to select the instantly claimed strain. Moré teaches the instantly claimed strain indeed secretes the polyamines required in Eiichi’s composition.
The applicant argues that Eiichi’s invention is to specific Saccharomyces enriched for polyamine content and thus selecting another species (strain) would go against Eiichi’s teachings. Persons having ordinary skill would appreciate this strain to being optimized for polyamine content however would also recognize that it would not be the only functional equivalent. As Moré teaches the instant strain indeed secretes the required polyamines in measurable amounts and persons having ordinary skill could optimize the amount to be within effective ranges for treating the same diseases or for having the same activity.
The applicant argues that Madel’s teaching does not teach any indication of osetoblastogenesis. The applicant argues that the Office Action assumes that Eiichi’s framework is open to accepting any Saccharomyces strain, and thus substituting Madel’s Saccharomyces bouldardii would have been prima facie obvious. This however was not the argument made, rather the Saccharomyces species (strain) secreting the needed polyamines needed to increase bone volume would have been obvious. For the instant claims 1-2, 8, 8-11, one could include both strains of Eiichi and Madel to create a more comprehensive composition for treating said bone disorders as argued in the above Office Action. The applicant argues that Dr. Bernard (from the declaration filed) concludes that one cannot extrapolate the content of polyamine from one species to presumably one with lower polyamine content (being the instantly claimed strain). Dr. Bernard provides no evidence that the instantly claimed strain produces such lower polyamine content. As counter to this and as can be appreciated from Moré teachings, S. boulardii strain CNCM I-745 does indeed secrete this required polyamines in measurable amounts and thus could be used in a method of increasing bone formation, especially given that the prior art recognizes the therapeutic benefit. Optimizing the amount of polyamine to meet the required effective amount taught by Eiichi is prima facie obvious and well within the purview of any skilled artisan.
The applicant argues that one cannot substitute Madel’s strain with that of Eiichi to arrive at a composition that would have osteoblastogenesis activity. The Office articulated including both strains and not substituting one for the other. Eiichi already teaches that the composition would indeed promote bone formation.
Conclusion
Currently no claims are allowed.
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JACOB A BOECKELMANExaminer, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
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