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 .
Status of the Claims
Claims 1-12 and 15 are currently pending.
Claims 1, 6, 8, 9-12, and 15 are amended.
Claims 9-12 and 15 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 13 and 14 are cancelled.
Claims 1-8 have been considered on the merits.
Withdrawn Objections/Rejections
The objections made onto claims 6 and 8 are withdrawn in light of the amendments made onto the claims in the reply filed on 07/07/2026.
The rejections made onto claims 13 and 14 under 35 U.S.C. 101 are withdrawn in light of the amendments made onto the claims in the reply filed on 07/07/2026.
The rejections made onto claims 1-8 and 13-14 are withdrawn in light of the amendments made onto the claims in the reply filed on 07/07/2026.
New and Maintained Rejections Necessitated by Amendment
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.
Claims 1-8 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 has been amended to require closed “consists of” language, which has rendered the claim indefinite. Claim 1 describes the claimed product as “a tissue engineered bone graft” in the preamble. The body of claim 1 describes a decalcified bone matrix carrier and human bone marrow stromal stem cells (BMSCs), and later claims that “the concentration of BMSCs in the composite is 1 x 107 cells/cm3 – 1 x 108 cells/cm3”. Therefore, the actively claimed product of claim 1 appears to be a bone graft which consists of BMSCs, and only BMSCs due to the closed language of the claim. The claim then provides a product-by-process type phrase of “the graft is a chondroid graft formed by inoculating the BMSCs in the decalcified bone matrix carrier and subjected to in vitro chondrogenic induction culture for 0.5-8 weeks”, which additionally renders the claim scope indefinite for two distinct reasons. A first inconsistency is that the graft is described as a “bone graft” consisting only of BMSCs which is a wholistically different product than a “chondroid graft”. A “chondroid graft” describes a graft of cartilage by nature of the term, which is not interchangeable with the term “bone graft”, which describes a graft of bone. Bone and cartilage are distinct tissue types. A second inconsistency of claim 1 is the time frame at which the claimed product is being described. It is not clear if the claimed product is drawn to a bone graft containing BMSCs or if the claimed product is meant to be drawn to a product which begins as bone graft containing BMSCs which is subsequently differentiated into chondroid graft. Specifically, it is not clear based on the product-by-process limitation regarding the “chondroid graft” if the claimed product is a bone graft consisting of BMSCs or if the claimed product is intended to be a “chondroid graft”. The claim appears to be claiming both a starting product and a resultant product as the identical graft. Therefore, the type of graft that is claimed is generally indefinite.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4 and 7-8, are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Huang et al (US20120251609A1).
Claim Interpretation:
Claim 1 contains a product by process limitation in which the process of forming the graft by inoculating the BMSCs in the decalcified bone matric carrier and subjected to in vitro chondrogenic induction culture for 0.5-8 weeks, carries little patentable weight. It is only the product, which is anticipated by the prior art and not the process by which the product was made. This is because the final product (a tissue-engineered bone graft) is not distinguished by any particular features or characteristics resulting from the process by which it was made. As such, the limitations of the claimed process of inoculating the BMSCs in the decalcified bone matric carrier and subjected to in vitro chondrogenic induction culture for 0.5-8 weeks are met by any process of inoculating BMSCs in the prior art. Patentability of a product-by-process claim is determined by the novelty and nonobviousness of the claimed product itself without consideration of the process for making it which are encompassed by the claimed process of inoculating the BMSCs in the decalcified bone matric carrier and subjected to in vitro chondrogenic induction culture for 0.5-8 weeks of claim 1.
Regarding claim 1, Huang teaches a decalcified bone matrix carrier ([0001]) comprising human bone marrow stromal stem cells (BMSC) ([0081] and [0149]/Example 5). Huang teaches that the decalcification degree is at least between 95-80% demineralized ([0011]). Huang teaches that the thickness of the decalcified bone matrix is between 1-10 mm thick ([0099]). Huang teaches that the graft is a solid cell material composite and the concentration of BMSCs in the composite is 2 x 107 cells/ml (identical units to cells/cm3) ([0149]). Additionally, Huang teaches that the graft may contain, but does not require, chondrocytes meeting the limitations of “chondroid graft” ([0081]). Huang teaches the graft is formed by inoculating the decalcified bone matrix carrier with BMSCs and subjecting the carrier to in vitro culture for a range of 1 day to about 4 weeks ([0097]).
Regarding claim 2, Huang teaches that the decalcification degree is at least between 95-80% demineralized ([0011]).
Regarding claim 3, Huang teaches that the thickness of the decalcified bone matrix is between 1-10 mm thick ([0099]).
Regarding claim 4, Huang teaches that the cells are autologous ([0081]).
Regarding claim 7, Huang teaches that the graft is a solid cell material composite and the concentration of BMSCs in the composite is 2 x 107 cells/ml (identical units to cells/cm3) ([0149]).
Regarding claim 8, Huang teaches that the bone graft can be used to treat bones of the skull, which meets the claim limitation that the bone graft is used to treat a defect in the inferior turbinate ([0110]). Huang also teaches that the graft can be sized and can conform to the shape of the implant site ([0010]).
Therefore, Huang anticipates claims 1-4 and 7-8.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al (US20120251609A1), in view of Caplan et al (US5486359A).
Regarding claims 5-6, the limitations of the independent claim 1 are taught above.
Huang teaches a decalcified bone matrix carrier ([0001]) comprising human bone marrow stromal stem cells (BMSC) ([0081] and [0149]/Example 5).
Huang does not specify the type of bone the bone marrow is derived from. Huang does not teach that the BMSCs are derived from cancellous bone as required by claim 5. Huang does not teach that the cancellous bone is ilium, sternum, or ribs as required by claim 6.
However, Caplan teaches methods of isolating human mesenchymal stem cells for therapeutic uses. Caplan teaches the use of the human MSCs derived from the iliac crest, part of the ilium, in bone grafts which formed bone in 3 different samples (col. 20, para 2-3).
Regarding claims 5-6, Caplan teaches that bone marrow is the soft tissue occupying the medullary cavities of long bones, some haversian canals, and spaces between trabeculae of cancellous/spongy bone (col. 5, para 2-3). Caplan teaches that MSCs can be derived from bone marrow obtained from the iliac crest which is the top part of the ilium, ribs, spine, femora, tibiae, or other medullary spaces (col. 2, para 2).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the bone graft comprising human bone marrow derived mesenchymal stem cells taught by Huang with the bone marrow derived from cancellous bones taught by Caplan to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Huang teaches the use of bone marrow derived MSCs and Caplan teaches the use of the human MSCs derived from the iliac crest, part of the ilium, in bone grafts which formed bone in 3 different samples (col. 20, para 2-3). One of ordinary skill in the art would have a reasonable expectation of success when combining Huang with Caplan because both teach the necessary information to produce bone grafts from bone marrow derived MSCs.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 07/07/2026 have been fully considered but they are not persuasive.
Applicant argues (Remarks, pg. 6) that the “tissue-engineered bone graft is totally different from the demineralized cancellous bone matrix disclosed by Huang et al” because “the tissue-engineered bone graft as claimed in the present application is a chondroid graft formed by inoculating the BMSCs in the decalcified bone matrix carrier and subjected to in vitro chondrogenic induction culture”. Further Applicant asserts that “the chondroid graft of the present application is transformed by [BMSC]s under the condition of chondrogenic induction, rather than further containing chondrocytes as taught by Huang. The tissue-engineered bone graft as claimed in the present application does not contain additional chondrocytes”.
In response, this argument is not found persuasive. Applicant’s argument highlights the indefiniteness of claim 1 which are described in detail in the 35 U.S.C. 112(b) rejection above. Claim 1 is drawn to a product of a bone graft consisting of decalcified bone matrix carrier and BMSCs, and the product-by-process limitation requiring that “the graft is a chondroid graft formed by inoculating the BMSCs in the decalcified bone matrix carrier and subjected to in vitro chondrogenic induction culture for 0.5-8 weeks” appears to alter the claimed bone graft containing BMSCs to a graft containing BMSCs which have been induced to differentiate into chondrocyte-like cells, therefore the claimed “chondroid graft” no longer consists of BMSCs but would also contain chondrocyte-like cells differentiated from the BMSCs. Further, Applicant argues specifically that “the tissue-engineered bone graft as claimed in the present application does not contain additional chondrocytes” (pg. 6). It is not clear if the term “additional chondrocytes” is meant to refer to fully differentiated chondrocytes added in addition to BMSCs or if the term is meant to imply that the BMSCs which are subjected to chondrogenic induction as claimed in lines 9-10 of claim 1 do not produce chondrocytes/chondrocyte-like cells. Additionally, it appears that Applicant is employing the terms “bone graft” and “chondroid graft” interchangeably, which goes against the typical use of these terms in the art. Therefore, the arguments are not found persuasive.
Applicant argues (Remarks, pg. 7) that the claimed graft has a degree of flexibility “which is convenient for trimming into a graft with suitable size and shape”.
In response, the argument is not found persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a degree of flexibility) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Therefore, the argument is not found persuasive.
Applicant argues (Remarks, pg. 7) that method 3 of the specification provides the best results when the product is used and that “the tissue-engineered bone graft prepared by Method 3 is closer to cartilage” and the graft of the instant invention forms “a shape and hardness that is closer to natural inferior turbinates” when implanted.
In response, the argument is not found persuasive. In response to applicant's argument that the claimed engineered graft forms a shape and hardness that is closer to natural inferior turbinates” when used for implantation, 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. Therefore, the argument is not found persuasive.
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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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