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 .
Claims 1-4, 9, 10, 12-14 and 21 are pending in this application, Claims 1-4, 9 and 10 are acknowledged as withdrawn, Claims 12-14 and 21 were examined on their merits.
The rejection of Claim 21 under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AlA), first paragraph, as failing to comply with the written description requirement, has been withdrawn due to the Applicant’s amendments to the claims filed 11/24/2025.
The rejection of Claim 14 under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AlA),
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to pre-AlA 35 U.S.C. 112, the applicant), regards as the invention, has been withdrawn due to the Applicant’s amendments to the claims filed 11/24/2025.
Claim Rejections - 35 USC § 103
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.
Claims 12-14 and 21 are rejected under 35 U.S.C. § 103 as being
unpatentable over lbusuki et al. (2007) in view of Gomez et al. (2012), Vidal et al. (WO
98/44809), and further in view of Karamichos et al. (2009), all of record.
lbusuki et al. teaches a non-crosslinked composition comprising: 5 mg/ml (0.5%)
Type-1 Collagen gel solution (ICN Biomedical), an inducible cross-linking agent (0.1,
0.25, 0.50 or 100 mM riboflavin and 10, 20, 50 or 100 µM Rose Bengal) and living chondrocytes or fibroblasts (Pg. 1996, Column 1, Lines 18-21 and Lines 34-37 and Column 2, Lines 18-44 and Pg. 1997, Fig. 1 and Pg. 1998, Fig. 3), and reading on Claims 12, 13, 14 and 21.
With regard to Claim 21, Examiner notes that the mixture of collagen
solution, cross-linking agent and cells occurs prior to exposure to light initiated cross-
linking or gelation of the mixture.
Therefore, the un-crosslinked solution would be considered to be non-solidified or “injectable”, giving the term its’ broadest, reasonable interpretation.
With regard to the limitation of Claim 21, that the collagen be “acid extracted’, this is a product-by-process limitation and has been construed consistent with the MPEP at 2113, I. and Il. The bovine collagen gel of lbusuki et al. is the same as the claimed acid-extracted collagen gel. If this is not the case, the ordinary artisan would have found it obvious to use acid-extracted bovine collagen because Gomez et al. teaches the use of acetic acid to extract collagen from rat tails (Pg. 150, Line 1 and Table 1), additional claim construction of record.
The teachings of lbusuki et al. and Gomez et al. were discussed above.
Neither lbusuki et al. or Gomez et al. taught an injectable collagen gel composition comprising a base, wherein the base is NaOH, or wherein the collagen is included at a concentration of 15 mg/mL, as required by Claim 21.
Vidal et al. teaches an injectable, collagen composition comprising substantially 100% type I collagen, having a pH in the range of from about 3-6 and a collagen concentration of from about 20-90 mg/mL (reading on a concentration of 15 mg/mL which is “about” 20 mg/mL (Pg. 20, Claim 1) wherein the collagen may be crosslinked or non-crosslinked (Pg. 14, Lines 7-9).
Karamichos et al. teaches that rat tail type I collagen is diluted with acetic acid and neutralized with 1M sodium hydroxide (NaOH) prior to the addition of living cells to the collagen mixture (Pg. 2, Lines 30-34).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the amount of collagen in the composition of lbusuki et al. and Gomez et al. whom utilized acid extracted, non- crosslinked type I collagen at a concentration of 5 mg/ml with the amount of collagen in the composition of Vidal et al., whom teaches an injectable, non-crosslinked type I collagen concentration of 20 mg/ml because this is no more than the simple substitution of one known element (5 mg/ml of type-1 collagen gel) for another (20 mg/ml type-1 collagen gel) to obtain predictable results (cross-linkable, injectable collagen gels). See the MPEP at 2141, Ill. Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to prepare a type I collagen gel with the appropriate amount of collagen. There would have been a reasonable expectation of success in making this combination because both the lbusuki and Vidal references are drawn to the same field of endeavor, that is, injectable non- crosslinked collagen gels.
It would have been further obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the collagen gel composition of lbusuki et al., Gomez et al. and Vidal et al. with the neutralization of the acidic collagen prior to cell addition as taught by Karamichos et al. above, because this would provide a physiologically neutral collagen gel. Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to neutralize the acidic collagen gel prior to addition for cells to create a physiological environment.
Response to Arguments
Applicant’s arguments, see Remarks, filed 11/24/2025, with respect to the rejection of Claims 12-14 and 21 have been fully considered and are persuasive. The rejections have been withdrawn.
The remaining arguments have been considered only insofar as they apply to the current rejections.
The Applicant argues that Ibusuki and Gomez do not teach an injectable collagen composition with the claimed amount of collagen (Remarks, Pg. 6, Lines 8-20).
In response to Applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this instance, Ibusuki teaches a composition comprising collagen at 5-8 mg/mL due to the poor water solubility of collagen while Gomez teaches that collagen can be dissolved in acid (acid having a low pH and thus overcoming poor water solubility and preventing spontaneous gelation due to increased pH). Thus, the ordinary artisan would recognize that acidic conditions are required to prevent spontaneous gelation of collagen at concentrations at least in excess of 8 mg/mL. The
Examiner notes that the ordinary artisan would also have been in possession of the
teachings of Vidal of an injectable, collagen composition comprising substantially 100%
type I collagen having a pH in the range of from about 3-6 (an acidic pH range) and a
collagen concentration of from about 20-90 mg/mL reading on a concentration of 15 mg/mL which is “about” 20 mg/mL) (Pg. 20, Claim 1). That is, the values are so close (15 mg/mL vs. 20 mg/mL) that the ordinary artisan would expect the compositions to have the same properties and characteristics. See the MPEP at 2144.05, I. Therefore, the ordinary artisan looking to prepare an injectable, collagen gel solution with the claimed collagen concentration would have been motivated to modify the “low” collagen concentration of lbusuki in view of the higher collagen concentration of Vidal to prepare an injectable, type I collagen gel with the desired concentration of collagen.
The Applicant argues that the composition of Vidal allegedly possesses different characteristics from the composition of Ibusuki. Applicant asserts that Ibusuki teaches a lower collagen concentration solution (5-8 mg/mL) than claimed (15 mg/mL) while Vidal discloses a high collagen concentration suspension (20-90 mg/mL) (Remarks, Pg. 6, Lines 26-28 and Pg. 7, Lines 1-7).
This is not found to be persuasive for the following reasons, clearly Ibusuki either teaches or makes obvious in view of Gomez that acid can be used to dissolve collagen into a solution. Just as clearly, Vidal teaches processing tendon fragments (containing collagen) with acid, see Pg. 9, Lines 4-8. Therefore, the ordinary artisan would have readily grasped that both methods are used to produce an acid-extracted collagen solution and Vidal discloses an acid-extracted collagen solution at a concentration which is close enough to the claimed collagen concentration to render it prima facie obvious. That fact that Vidal later includes an additional step of producing a collagen suspension from the collagen solution is immaterial to this fact.
The Applicant argues that the Examiner has allegedly mischaracterized the teachings of Vidal in that the reference’s cited passage does not teach a collagen solution with a collagen concentration of 20-90 mg/mL because the cited concentration only relates to a collagen suspension (Remarks, Pg. 7, Lines 18-34 and Pg. 8, Lines 1-18).
This is not found to be persuasive for the following reasons, as discussed above, Vidal teaches processing tendon fragments (containing collagen) with acid to produce a collagen solution which is later filtered (Pg. 9, Lines 4-8, 10-11, 16-17 and 20-21) and having a collagen concentration of 20-90mg/mL (Pg. 20, Claim 1. Thus, the concentration of collagen in the composition is the same (20-90mg/mL) whether in solution or in suspension, as collagen is neither added or removed. That Vidal later includes an additional step of producing a collagen suspension from the collagen solution is immaterial to this fact.
The Applicant argues that there would have been no motivation to combine the cited prior art because Vidal teaches acid dissolved collagen which is later formed into a suspension by raising the pH. Applicant concludes that the ordinary artisan would not have combined the cited prior art because Ibusuki teaches a collagen concentration below that claimed, Karamichos teaches acid dissolved collagen at a low concentration neutralized with NaOH and Vidal teaches a high concentration collagen suspension formed by raising the pH of an acid dissolved collagen solution (Remarks, Pg. 8, Lines 21-30 and Pg. 9, Lines 1-11).
This is not found to be persuasive for the following reasons, as discussed in the prior action and above, it would have been obvious to one of ordinary skill in the art to substitute the amount of collagen in the composition of lbusuki and Gomez whom utilized acid extracted, non-crosslinked type I collagen at a concentration of 5-8 mg/ml with the amount of collagen in the composition of Vidal, whom teaches an injectable,
non-crosslinked type I collagen concentration solution of 30-90 mg/ml because this is no more than the simple substitution of one known element (5-8 mg/ml of type-1 collagen gel) for another (20 mg/ml type-1 collagen gel) to obtain predictable results (cross-linkable, injectable collagen gels). See the MPEP at 2141, Ill. Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to prepare a type I collagen gel with the desired appropriate amount of collagen. It would have been further obvious to one of ordinary skill in the art to modify the collagen gel composition of lbusuki, Gomez and Vidal with the neutralization of the acidic collagen prior to cell addition as taught by Karamichos above, because this would provide a physiologically neutral collagen gel. Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to neutralize the acidic collagen gel prior to addition for cells to create a physiological environment.
The Applicant argues that the claimed composition has the alleged “unexpected” results of preserving the ability of the annulus fibrosis to retain nuclear tissue in the disc
space, thereby preventing degeneration of the intervertebral disc, improve retention of
nucleus pulposus (NP) size and disc height for up to 5 or more weeks after needle
puncture; and the 0.5 mM riboflavin group retained most of its nuclear tissue according
to NP voxel counts and histological cross-sectional area measurements.
Applicant further cites the comparative data in the Declaration filed 01/21/2020, as supporting the alleged unexpected results of using acid-extracted collagen in a composition containing riboflavin. i.e., that non-acid extracted collagen failed to form a cohesive gel that could be removed from a mold (Remarks, Pg. 9, Lines 13-28 and Pg. 10, Lines 1-7).
This is not found to be persuasive for the following reasons, the Applicant has not
provided a comparison with the closest prior art commensurate in scope with the claims,
which would be the composition of lbusuki. The Examiner notes that the collagen formulation utilized in the disclosure at Pg. 17, Paragraph [0060] of the Specification as published differs from the claimed composition in that it has been first lyophilized and then reconstituted in acetic acid and then mixed with DPBS and requires a particular concentration of NaOH (1N). Thus, the showing in the disclosure does not appear to be commensurate in scope with the claimed composition. With regard to the alleged “unexpected” structural characteristics of an acid extracted collagen gel containing riboflavin referenced in the Declaration filed 01/21/2020, the composition of lbusuki would meet these limitations as it is structurally the same as the claimed composition and must therefore have the same properties and characteristics, which would therefore not be unexpected. That is, regarding the limitation that the collagen be “acid extracted’, this is a product-by-process limitation and has been construed consistent with the MPEP at 2113, I. and Il.
The bovine collagen gel of lbusuki is the same as the claimed acid-extracted collagen gel. If this is not the case, the ordinary artisan would have found it obvious to use acid-extracted bovine collagen because Gomez teaches the use of acetic acid to extract collagen from rat tails (Pg. 150, Line 1 and Table 1).
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653