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
Applicant’s submission filed 22 June 2026 has been entered. Claims 1-17, 19-21, and 23-28 are pending. Claims 1-2, 4, 9, and 28 have been amended. 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merits continues for claims 1-10 and 27-28 as being drawn to the elected invention, with claims 11-17, 19-21, and 23-26 withdrawn for reading on the non-elected invention.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: Rejection of claim 4 under 35 USC 112(b)
Applicant’s amendment to instant claim 4 corrects the antecedent basis of the claim. Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-10 and 27-28 under 35 USC 103 over Semler et al in view of Benham and Wang et al
Applicant has amended independent claim 1 to require the osteogenic composition to comprise growth-factor augmented cortical bone comprising demineralized cortical bone bound with a plurality of growth factors derived from demineralized cortical bone by acidic extraction of the demineralized cortical bone to produce a growth factor rich solution comprising a native mixture of plurality of growth factors. With that, Applicant’s arguments filed 22 June 2026 have been fully considered but are not found persuasive.
Applicant has traversed the rejection, asserting on Pages 9-11 that Semler et al fail to teach a native mixture of growth factors derived from demineralized cortical bone. In response, the Examiner respectfully submits that the secondary reference of Benham teaches a native mixture of growth factors that are derived from demineralized bone, including demineralized cortical bone. See, for example, Paragraphs [072]-[073] of Benham.
Applicant has further traversed the rejection, asserting in Pages 11-14 of the Remarks filed 22 June 2026 that Benham fails to teach the acidic extraction of growth factors from already-demineralized bone. More specifically, Applicant asserts that Benham either teach the chaotropic/detergent extraction of growth factors from demineralized bone matrix, or the acidic extraction of growth factor from mineralized or partially demineralized bone. In response, the Examiner respectfully submits that the newly added limitation of “a plurality of growth factors derived from demineralized cortical bone by acidic extraction of the demineralized cortical bone to produce a growth factor rich solution comprising a native mixture of plurality of growth factors” is a product-by-process limitation (emphasis added). Accordingly, the final structure of the osteogenic composition is not altered due to utilizing an acidic extraction technique on the demineralized cortical bone to extract the native mixture of a plurality of growth factors, as the growth factors are renatured to their active and native three-dimensional structure following the extraction technique. See, for example, Paragraphs [074]-[076] of Benham. Therefore, the teachings of Benham regarding the chaotropic/detergent extraction of growth factors from demineralized bone matrix fulfills the recited limitation.
Furthermore, in regards to Applicant’s arguments on Page 13 of the Remarks filed 22 June 2026, it is of note that Benham does not treat the growth factors released during the demineralization process as “waste”, and instead provides techniques of recovering the osteoinductive factors that are normally lost during the demineralization process.
Applicant has further traversed the rejection, asserting in Pages 13-14 of the Remarks filed 22 June 2026 that the combination of Semler et al and Benham fails to teach that the native mixture of growth factors is “bound” to the demineralized cortical bone. In response, the Examiner respectfully submits that Benham teaches that the growth factors are adhered onto a demineralized cortical bone carrier. See, for example, Paragraphs [039]-[041], [048], [0185]-[0186] of Benham.
Applicant has further traversed the rejection, asserting in Pages 14-15 of the Remarks filed 22 June 2026 that the combination of Semler et al and Benham fail to teach the incubation, draining, and rinsing of the growth-factor augmented cortical bone, as required in instant claim 9. In response, the Examiner respectfully submits that the limitations of instant claim 9 are product-by-process limitations. Accordingly, the final structure of the osteogenic composition is only altered in that the growth-factor augmented cortical bone is required to only have growth factors that are stably associated with the demineralized cortical bone matrix. As Benham teaches that the growth factors are adsorbed onto the carrier – or demineralized cortical bone matrix – and can be washed, this therefore fulfills the recited limitations of the instant claim. See, for example, Paragraphs [039]-[041], [048], [082], [0185]-[0186] of Benham.
Applicant has lastly traversed the rejection, asserting in Pages 15-16 of the Remarks filed 22 June 2026 that the combination of all limitations in amended claim 1 – including the native mixture of growth factors derived by acidic extraction from demineralized cortical bone, bound to the demineralized cortical bone carrier, combined with the cancellous bone component in a cryopreserved composition – is not taught or suggested by any combination of the cited references. In response, the Examiner respectfully directs Applicant to the previous discussions regarding the native mixture of growth factors derived by acidic extraction from demineralized cortical bone that are bound to the demineralized cortical bone carrier, as well as Pages 7-9 of the Office action filed 31 December 2025.
Therefore, the rejection is maintained and amended to encompass the claims as currently written.
New/Maintained Grounds of Rejection
Claim Objections
Claims 7-8 are objected to because of the following informalities:
Regarding claims 7-8: The instant claims are each objected to for reciting “demineralized bone” instead of “demineralized cortical bone” to match the recitation in parent claim 1.
Appropriate correction is required.
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 1-10 and 27-28 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.
Regarding claim 1: The instant claim recites the limitation, “wherein the growth-factor augmented demineralized cortical bone comprises a greater concentration of the plurality of growth factors bound to the demineralized cortical bone compared to a non-enhanced demineralized cortical bone from the same donor.” The scope of the claim is indefinite, as the metes and bounds of “a non-enhanced demineralized cortical bone” cannot be readily determined. It is also of note that a growth-factor augmented demineralized cortical bone is not necessarily synonymous with an “enhanced” demineralized cortical bone such that the direct comparison is to a “non-enhanced” demineralized cortical bone.
Instant claims 2-10 and 27-28 depend from independent claim 1 and fail to correct the deficiencies of the parent claim.
Appropriate correction is required.
Regarding claim 6: The instant claim recites the limitations “the demineralized cortical bone” and "the demineralized bone" in Line 2. There is insufficient antecedent basis for these limitation in the claim, as there are multiple recitations of “demineralized cortical bone” and “demineralized bone” within parent claim 1. See MPEP § 2173.05(e). Therefore, the ordinary artisan cannot readily determine the metes and bounds of the claim.
Appropriate correction is required.
Regarding claim 27: The instant claim recites the limitation “the enhanced demineralized cortical bone” in Line 3. There is insufficient antecedent basis for these limitation in the claim, as there is no prior recitation of an “enhanced demineralized cortical bone” within the instant claim or parent claim 1. See MPEP § 2173.05(e). Therefore, the ordinary artisan cannot readily determine the metes and bounds of the claim.
Appropriate correction is required.
The Examiner would also like to put Applicant on notice that the recitation of “non-enhanced demineralized cortical bone” will need to be addressed upon amending the recitation of “the enhanced demineralized cortical bone”. See the 35 USC 112(b) rejection above regarding claim 1.
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 7 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.
Regarding claim 7: The instant claim recites the limitation, “wherein the growth factors are obtained from demineralized bone that has been soaked in an acidic solution to extract the growth factors.” However, as parent claim 1 already requires the plurality of growth factors to be derived from demineralized cortical bone “by acidic extraction of the demineralized cortical bone to produce a growth factor rich solution comprising a native mixture of a plurality of growth factors”, the limitation of instant claim 7 does not further limit parent claim 1 from which it depends.
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.
Claim Interpretation
Claim 1 defines the growth factors within the growth-factor augmented cortical bone to be “a plurality of growth factors derived from demineralized cortical bone by acidic extraction of the demineralized cortical bone to produce a growth factor rich solution comprising a native mixture of a plurality of growth factors”. 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 by acidic extraction imparts any particular structure or significance to the growth factors, beyond the fact that the growth factors must be a mixture of growth factors that are 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 factor mixture includes those growth factors identified by Wang et al.
With that, claim 4 further defines the demineralized cortical 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 cortical 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 demineralized cortical bone subject to acidic extraction methods 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 claims.
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 requiring only growth factors that are stably bound to the demineralized cortical bone, with the elimination of unbound growth factors from the demineralized cortical bone via washing. 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 adherence of the plurality of growth factors to the demineralized cortical bone and subsequent washing of the resulting structure fulfills the limitation detailed in the instant claim – wherein the growth-factor augmented cortical bone is formed by adding the growth factor rich solution to the demineralized cortical bone and incubating for between about 1 hour and about 3 hours at between about 32°C and about 44°C, and draining and rinsing the demineralized cortical bone – 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 remain 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 mixture comprising a plurality of growth factors such that the supplemented demineralized cortical bone osteoinductive matrix comprises a greater concentration of the plurality of growth factors bound to the demineralized cortical bone compared to a non-supplemented 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 can be derived from demineralized cortical bone, and can include the growth factors of TGF-β, IGF-I, IGF-2, BMP-2, BMP-7, parathyroid hormone (PTH), and angiogenic factors (Paragraphs [039]-[041], [068]-[069], [072]-[076], [0128]).
Benham further discloses that the demineralized cortical bone-derived growth factors are adhered onto a demineralized cortical bone carrier (Paragraphs [039]-[041], [048], [0185]-[0186]).
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 and bound 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 bound 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 bound to the 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 plurality of growth factors are adhered onto the demineralized cortical bone by exposing the demineralized cortical bone to a solution comprising the plurality of growth factors (Paragraphs [097], [0157], [0185]). 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, as aforementioned, Semler et al as modified by Benham and Wang et al teach the adherence of a plurality of growth factors derived from demineralized cortical bone to the demineralized cortical bone carrier. Benham further discloses that the demineralized cortical bone carrier can be washed to remove weakly bound proteins (Paragraphs [071]-[075], [082], [097], [0115]). This therefore renders obvious the osteogenic composition of the instant claim for the same reasons as discussed in the rejection of claim 1.
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 adherence of a plurality of growth factors derived from demineralized cortical bone to the demineralized cortical bone carrier. 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
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 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
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