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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 19 November 2025 has been entered.
Status of the Claims
Applicant’s submission filed 08 November 2025 has been entered. Claims 1-17, 19-21, and 23-28 are pending. Claims 1 and 27-28 have been amended, with support for the amendments found in at least Paragraph [0008] of the instant Specification. Therefore, prosecution on the merits continues for claims 1-10 and 27-28 as being drawn to the elected invention, with claims 11-17, 19-21, and 23-26 withdrawn for reading on the non-elected invention. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection of claims 27-28
Applicant’s amendments to instant claims 27-28 obviate the current objections of record.
Therefore, the objections are withdrawn.
RE: Rejection of claims 1-10 and 27-28 under 35 USC 103 over Semler et al in view of Govil
Applicant’s amendment to independent claim 1 necessitating the plurality of growth factors to be derived from demineralized cortical bone obviates the current rejection of record, as this is a newly presented limitation.
Therefore, the rejection is withdrawn.
However, Applicant’s remarks are addressed in so far as they are applicable to the claims as amended:
Applicant has traversed the rejection, asserting on Pages 7-9 of the Remarks filed 08 November 2025 that the ordinary artisan would not have been motivated to source growth factors from demineralized cortical bone, as cancellous bone is more abundant in various growth factors when compared to cortical bone. In response, the Examiner respectfully submits that the claims are directed to “a plurality of growth factors derived from demineralized cortical bone”. Therefore, although the ratios and quantities of growth factors may differ between demineralized cancellous and cortical bone, the ordinary artisan would recognize that both demineralized cancellous and cortical bone contain a “plurality of growth factors”, and thereby would have been motivated to use either source since specific growth factors and quantities are not required by the claims.
New Grounds of Rejection
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.
Claim 4 is 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.
Regarding claim 4: The instant claim recites the limitation "the demineralized bone" in Lines 1-2. There is insufficient antecedent basis for this limitation in the claim, as there are multiple recitations of “demineralized bone” within parent claim 1. See MPEP § 2173.05(e). Therefore, the ordinary artisan cannot readily determine if Applicant is requiring the demineralized cortical bone within the growth-factor augmented cortical bone to be from an offcut, or rather the demineralized cortical bone from which the plurality of growth factors is derived from.
Appropriate correction is required.
Claim Interpretation
Claim 1 defines the growth factors within the growth-factor augmented cortical bone to be “a plurality of growth factors derived from a demineralized cortical bone”. This is a product-by-process limitation. Product-by-process limitations are only considered in so far as the method of production affects the structure of the final product. In the instant case, there is no evidence that the plurality of growth factors derived from demineralized cortical bone imparts any particular structure or significance to the growth factors, beyond the fact that the growth factors must be the same as those growth factors found in demineralized cortical bone, as growth factors are individual proteins all having identified and specific structures. The Examiner notes that the instant Specification does not define nor provide an exhaustive list of what growth factors are obtained from demineralized cortical bone. However, growth factors that are found in demineralized cortical bone include BMP-2, BMP-7, PDGF-BB, FGF-1, FGF-2, IGF-1, TGF-β, and VEGF. See Table 1 on Page 3 of Wang et al (MTF Biologics | ORTHOFIX White Paper, 2019, of record). Thus, the claim is interpreted as requiring ”a plurality of growth factors derived from demineralized cortical bone” to be from any source, so long as the growth factors include those identified by Wang et al.
With that, claim 4 further defines the demineralized bone from which the plurality of growth factors are obtained to be an offcut. This is a product-by-process claim. In the instant case, there is no evidence that the source of the demineralized bone – especially being an offcut or leftover stub of bone – imparts any particular structure or significance to the derived growth factors. Thus, the claim will be interpreted the same as instant claim 1, wherein the addition of “a plurality of growth factors derived from demineralized cortical bone” from any source fulfills the limitation detailed in the instant claim.
Claims 7-8 further describe the process in which the plurality of growth factors are obtained. These are product-by-process claims. Product-by-process claims are only considered in so far as the method of production affects the structure of the final product. In the instant case, there is no evidence that the plurality of growth factors derived from processed demineralized cortical bone imparts any particular structure or significance to the growth factors, as growth factors are individual substances all having identified and specific structures. Thus, the claims will be interpreted as if the addition of ”a plurality of growth factors derived from demineralized cortical bone” can be from any source, so long as the growth factors include those identified by Wang et al, fulfills the limitation detailed in the instant claim.
Claims 9-10 further describe the processes in which the growth-factor augmented cortical bone is formed. These are product-by-process claims. Product-by-process claims are only considered in so far as the method of production affects the structure of the final product. In the instant case, there is no evidence that the growth-factor augmented cortical bone formed via the outlined process in claim 9 imparts any particular structure or significance to the growth-factor augmented cortical bone other than the combining of the growth factors with the demineralized cortical bone. Likewise, there is no evidence that the growth-factor augmented cortical bone formed via the outlined process in claim 10 imparts any particular structure or significance to the growth-factor augmented cortical bone other than it being a lyophilized final product. Therefore, claim 9 will be interpreted as if the addition of the plurality of growth factors to the demineralized cortical bone fulfills the limitation detailed in the instant claim – wherein the growth-factor augmented cortical bone is formed by adding growth factors to the demineralized bone and incubating for between about 1 hours and about 3 hours at between about 32°C and about 44°C – while claim 10 will be interpreted as if the formation of a lyophilized growth-factor augmented cortical bone product fulfills the limitation detailed in the instant claim – wherein the growth-factor augmented cortical bone is formed by neutralizing the growth factors with a basic solution, dialyzing the solution, adding the demineralized cortical bone, and lyophilizing.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 1-10 and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Semler et al (US 10,130,736 B1, of record) in view of Benham (WO 2007/053850 A2, of record on IDS filed 19 November 2025) and Wang et al (MTF Biologics | ORTHOFIX White Paper, 2019, of record).
Semler et al and Benham are both considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 1 and 27: The instant claim includes product-by-process language. The effect of the product-by-process language is discussed above – see Claim Interpretation – and included herein.
Semler et al disclose implantable compositions for bone repair containing an osteoconductive matrix, endogenous cells, and an osteoinductive matrix (Column 1, Field of Invention).
As such, Semler et al disclose an implantable composition, the implantable composition comprised of a cancellous bone osteoconductive matrix comprising adherent endogenous osteogenic cells, as well as a demineralized cortical bone osteoinductive matrix (Column 46, Lines 27-33; Column 47, Lines 38-39; Column 48, Lines 17-22; Column 49, Lines 35-37; Column 292, Lines 5-17). It is of note that the demineralized cortical bone osteoinductive matrix is further supplemented with osteogenic growth factors, including bone morphogenetic protein-2 (BMP-2) (Column 49, Lines 44-55; Column 263, Example 3.3).
Semler et al further disclose that the implantable composition is cryopreserved (Column 258, Example 1).
Semler et al do not disclose or reduce to practice the supplementation of the demineralized cortical bone osteoinductive matrix with a plurality of growth factors such that the supplemented demineralized cortical bone osteoinductive matrix comprises a greater concentration of the plurality of growth factors compared to a non-enhanced demineralized cortical bone osteoinductive matrix from the same donor, as required by instant claim 1.
Benham, however, discloses an osteoinductive composition, wherein the osteoinductive composition comprises osteoinductive factors, such those extracted from demineralized bone (Abstract).
As such, Benham discloses that the osteoinductive factors are derived from demineralized cortical bone, and includes the growth factors of TGF-β, IGF-I, IGF-2, BMP-2, BMP-7, parathyroid hormone (PTH), and angiogenic factors (Paragraphs [068]-[069], [0128]).
Further, Wang et al disclose that growth factors that are found in demineralized cortical bone include BMP-2, BMP-7, PDGF-BB, FGF-1, FGF-2, IGF-1, TGF-β, and VEGF (Table 1).
Therefore, it would have been prima facie obvious to have modified the demineralized cortical bone osteoinductive matrix of Semler et al such that is it supplemented with a plurality of growth factors derived from demineralized cortical bone, as detailed in Benham and Wang et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to supplement the demineralized cortical bone with the plurality of growth factors, as it enhances the osteoinductive properties of the demineralized cortical bone (Benham: Paragraphs [037], [056], [061], [064], [083], [0139], [0186]), and would have had a reasonable expectation of success given that the disclosure of Semler et al (Column 49, Lines 44-55; Column 263, Example 3.3) and Benham (Paragraphs [037], [040], [048], [068], [0128]) are both concerned with the generation of bone implants comprising demineralized cortical bone that has been supplemented with growth factor(s). See MPEP § 2143(I)(G).
Consequently, Semler et al as modified by Benham and Wang et al render obvious a cryopreserved implantable composition comprised of a cancellous bone osteoconductive matrix comprising adherent endogenous osteogenic cells, as well as a demineralized cortical bone osteoinductive matrix that has been further supplemented with an effective amount of a plurality of growth factors derived from demineralized cortical bone such that the osteoinductive properties of the demineralized cortical bone is enhanced (claim 27). As Semler et al fail to disclose that the cancellous bone comprised within the cryopreserved implantable composition is contacted with a loosening agent, and the concentration of demineralized cortical bone-derived growth factors within the supplemented – or enhanced – demineralized cortical bone is inherently greater than demineralized cortical bone that has not been supplemented with the plurality of growth factors, this therefore renders obvious the osteogenic composition of instant claim 1.
Regarding claim 2: Following the discussion of claim 1, Benham further discloses that the demineralized cortical bone is exposed to a solution comprising the plurality of growth factors (Paragraphs [097], [0157]). This therefore renders obvious the osteogenic composition of the instant claim for the same reasons as discussed in the rejection of instant claim 1.
Regarding claim 3: Following the discussion of claim 1, Semler et al further disclose that the demineralized cortical bone is milled from human bone (Columns 273-274, Example 7). This therefore reads on the osteogenic composition of the instant claim.
Regarding claims 4 and 7-8: Claims 4 and 7-8 are product-by-process limitations further describing the source of the growth factors. See Claim Interpretation section above. Accordingly, the source of the growth factors does not change the factors, per se. Therefore, claims 4 and 7-8 are rejected for the same reason as instant claim 1.
Regarding claim 5: Following the discussion of claim 1, Semler et al further disclose that the cancellous bone is milled from human bone (Column 50, Lines 30-32). This therefore reads on the osteogenic composition of the instant claim.
Regarding claim 6: Following the discussion of claim 1, Semler et al further disclose that the osteoinductive matrix – which comprises the demineralized bone – is prepared from the same source of bone as the osteoconductive matrix – which comprises the cancellous bone (Column 115, Lines 49-57). This therefore reads on the osteogenic composition of the instant claim.
Regarding claim 9: The instant claim is a product-by-process limitation further describing the process in which the growth-factor augmented cortical bone is formed. See Claim Interpretation section above. Accordingly, the means of producing the growth-factor augmented cortical bone does not necessarily change the final product, per se. Therefore, the supplementation of the demineralized cortical bone with the plurality of growth factors as taught by Semler et al in view of Benham is sufficient to render obvious the osteogenic composition of the instant claim.
Regarding claim 10: The instant claim includes product-by-process language. The effect of the product-by-process language is discussed above – see Claim Interpretation – and included herein.
Accordingly, as aforementioned, Semler et al as modified by Benham and Wang et al teach the addition of a plurality of growth factors derived from demineralized cortical bone to the demineralized cortical bone. Benham further discloses that the growth factors are added to the demineralized cortical bone carrier prior to be lyophilized (Paragraphs [0171], [0185], [0188]).
Given the product-by-process language, this therefore renders obvious the osteogenic composition of the instant claim.
Regarding claim 28: Following the discussion of claim 1, Benham further discloses that the addition of the plurality of osteoinductive growth factors to the demineralized cortical bone supports and promotes the formation – or regeneration – of bone (Paragraphs [054], [0186], [0190], [0198]). This therefore renders obvious the osteogenic composition of the instant claim for the same reasons as discussed in the rejection of instant claim 1.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633