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 .
Response to Amendment
The amendment filed 07/27/2026, amending claims 1 and 3 is acknowledged.
Claims 1-6, 8-11, and 21-23 are pending and under examination.
Withdrawn Rejections
The rejection of Claims 1-4 and 6-11 are rejected under 35 U.S.C. 103 as being unpatentable over Shi is withdrawn.
The rejection of Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Shi in further view of Weszl et al. is withdrawn.
The rejection of Claims 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Shi in further view of Ginis et al. is withdrawn.
Applicant added the new limitation of “the culturing the stem-cell seeded allograft occurs for a limited predetermined time of about 1 to 2 hrs on a shaker plate at 125 rpm” to base claim 1, which is not taught by Shi.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/27/2026 is considered by the examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application provisional application 63/193,153 filed on 05/26/2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Claim Interpretation
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrase "for application to a bone treatment site" in claim 1 is an intended use limitation, which does not contain any further structural limitations with respect to the claimed method for making a bone augmentation composition (see MPEP §2114).
Claim Rejections - 35 USC § 112(a) – Modified due to amendment
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-6, 8-11, and 21-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites the method for making a bone augmentation composition having the function of resulting in 50-90% survival of the cell population after thawing.
Claim 2 recites the method for making a bone augmentation composition having the function of resulting in a surviving stem cell population in the bone augmentation composition between 1 and 5 x 10^5 cells/ml.
Either these are inherent property(ies) of (that naturally flows from) the method steps of claim 1, or it is not.
The claim denotes that not all of the structures/method steps of the independent claim are able to achieve the functional property(ies) recited in the dependent claim(s).
To the extent it is not an inherent property (that naturally flows) from the product/method of the independent claim, then something must change. The claim is considered to lack adequate written description for failing to recite the structure that is necessary and sufficient to cause the recited functional language.
The limitations “wherein a surviving stem cell population in the bone augmentation composition after thawing is between 50% and 90% of an initial stem cell population in the bone augmentation composition prior to freezing” (claim 1) and “wherein the surviving stem cell population in the bone augmentation composition is between 1 and 5 x 10^5 cells/ml” merely states functional characteristics without providing any indication about how the functional characteristics are provided. The functional characteristics do not follow from (are not inherent property(ies) of) the structure recited in the claim, so it is unclear whether the claim requires some other structure to be added to the composition to provide the functional characteristic. The specification fails to disclose what structural changes to the method is necessary and sufficient to cause the recited survival rate, and thus the ordinary artisan would not know what modification(s) must be made in order to fulfill the instant recitation.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims fail to recite, and the specification fails to disclose, a nexus between the method steps of claim 1 and the corresponding functional property(ies) of
50% to 90% of an initial stem cell population surviving after thawing, and
Between 1 and 5 x 10^5 cells/ml in the bone augmentation surviving.
For example, are the resulting functional properties dependent upon the cell number in the seeding step (see also claims 2 and 5)? Upon the stem cell solution formulary? The amount of time cultured? The cryopreservation medium formulary and/or freezing protocol? Is it dependent upon the thawing protocol?
The response filed 07/27/2026, the Applicant argues that the functional outcome of 50% to 90% of an initial stem cell population surviving after thawing relies on the structure of culturing the stem cell seeded allograft for about 1 to 2 hours, and cite Example 5 and Fig. 8 of the specification for support for the structure/function nexus. However, these working examples and results do not teach how an artisan would arrive at a survival rate of about 90%. Fig. 8 shows at most 60% of the initial stem cell population surviving (see also pg. 10 of Remarks).
Additionally, the working examples of the specification point to other variables such as dynamic vs static seeding (Fig. 5), seeding cell concentration (Fig. 6) and seeding density (Fig. 7) effecting the survival rate/number of cells surviving.
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Martin, W. Blake, et al. "Methods of cryoprotectant preservation: allogeneic cellular bone grafts and potential effects." BioMed Research International 2019.1 (2019): 5025398. is considered relevant prior art for reviewing methods of cryoprotectant preservation of allogeneic cellular bone grafts. Martin et al. notes: “It is necessary that the addition and removal of the cryoprotectants is controlled to preserve cell viability, cell differentiation, and cell signaling [9–14]. As low freezing process of about -1 °C/min is commonly used for freezing so that most of the intracellular water has enough time to diffuse into the extracellular space prior to ice crystal formation [11–13]. Freezing too quickly will result in more ice formation within the cells and lead to more cell death [11–13]. For intracellular cryoprotectants, freezing too slow results in long-term exposure to high intracellular cryoprotectant concentrations as the cells are dehydrated and experience severe volume shrinkage [11-13]” (pg. 2, col 2, para 1). While Martin et al. largely focuses on the role of cryoprotectants such as DMSO in cell viability, Martin et al. teaches that there are a multitude of variables to be considered when cryopreserving bone grafts comprising hMSCs.
Claim Rejections - 35 USC § 112(b) - Modified and new, necessitated by amendment
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 1-6, 8-11, and 21-23 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 1 recites “the human mesenchymal stem cell solution”. It is unclear what the “stem cell solution” comprises. Specifically, does the solution comprise human mesenchymal stem cells? Is the solution a conditioned medium from cultured human mesenchymal stem cells? The metes and bounds of the solution are not clearly and precisely defined. It would be remedial to clarify what the solution refers to.
Claim 1 recites “wherein the seeding comprises a dynamic seeding where the hydrated allograft is agitated at least during application of the stem cell solution to the hydrated allograft”. It is unclear what “application” is referring to. Does “application” refer to the initial act of seeding? Or to the entirety of the seeding process (e.g., is the dynamic seeding the same as the “application”?). If it refers to the entire seeding step, does the ‘at least” refer to future steps? The metes and bounds of the method steps are not clearly and precisely defined. It would be remedial to clarify what “at least during application” entails.
In kind, claim 8 is similarly rejected.
Claim 1 recites “reducing stem cell attachment”. The recitation is indefinite because there is no prior recitation of stem cells in claim 1. While “human mesenchymal stem cell solution” is recited, the solution does not clearly require the presence of stem cells (e.g., the solution could be conditioned medium from the stem cells). Therefore, the metes and bounds of the claim is not clearly and precisely defined. It would be remedial to amend claim 1 to clearly recite that the stem cell solution comprises stem cells, if applicable.
Claim 11 recites “wherein the loose cortical fibers comprise an intertangled mixture of the cortical fibers.” There is insufficient antecedent basis for this limitation in the claim. The recitation is indefinite because there is no prior reference to loose cortical fibers in claim 11 or 1, and there is nothing implicit in claim 1, from which claim 11 depends upon, that would inherently require the recited cortical fibers in the base claim to be loose. Therefore, the metes and bounds of the claim is not clearly and precisely defined. It would be remedial to amend claim 1 to “the loose cortical fibers”.
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 10 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 10 recites “The method of claim 1, wherein the hydrated allograft containing the stem cell solution is frozen with dimethyl sulfoxide (DMSO) having a concentration of less than 10 weight percent.”
Claim 1 recites “incubating the stem-cell seeded allograft in a cryopreservation solution of 10% dimethyl sulfoxide for 30 mins prior to cryopreservation, freezing the stem-cell seeded allograft containing the cell culture media with the cryopreservation solution.”
The base claim already requires 10% DMSO to be present during freezing. As such, claim 10 fails to further limit base claim 1 from which it depends. Additionally, claim 10 recites a broader limitation than claim 1, with the recitation of “dimethyl sulfoxide (DMSO) having a concentration of less than 10 weight percent”.
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.
Response to Arguments
Applicant's arguments filed 07/27/2026 have been fully considered but they are not persuasive. The Applicant has filed a Declaration (Lauritzen; 07/27/2026). The Examiner acknowledges and has considered the Lauritzen Declaration. The statements by Lauritzen in the declaration were not found to be persuasive. Additionally, since the previous 103 rejections are withdrawn due to amendment, Applicant’s arguments with respect to Shi and Weszl have been considered but are moot.
The Applicant argues that Example 5 and Figure 8 of the disclosure demonstrate the nexus of the method steps/structure (e.g., culturing for about 1 to 2 hrs) and the corresponding functional property (e.g., 50% to 90% of an initial stem cell population surviving after thawing). While Example 5 and Fig. 8 do demonstrate a link between incubation time (interpreted to correspond to the culturing step of the claimed method, not the incubating step before freezing) and cell survival, the max survival seen appears to be about 60%. While this is within the recited range, it is still on the low end, and the instant disclosure doesn’t provide further guidance on how an artisan could achieve around 90% survival (e.g., what structural modifications would increase this percentage?). Additionally, regarding claim 2, which recites the surviving stem cell population in the bone augmentation composition being between 1 and 5 x 10^5 cells/ml, Example 5 teaches under 4x10^5 cells/ml surviving. The Examiner notes that Example 5 started with incubated grafts with 2 x 10^6 cell/ml. In comparison, Example 4/Figure 6 demonstrates that increases the seeding cell concentration led to an increased number of cells surviving.
In summary, while the Applicant states that incubating for 1 to 2 hrs is the structure that leads to the recited function, the specification teaches other variables affecting the functional outcomes of the claimed method, and also does not teach the claimed method resulting in functional outcomes recited in the claims, such as about 90% cell survival.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M JOHNSON whose telephone number is (703)756-1396. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ALLISON MARIE JOHNSON/Examiner, Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
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