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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 27, 2026 has been entered.
Status of the Claims
Claims 1-43 were originally filed May 18, 2022.
The amendment received November 21, 2022 amended claims 3, 8, 10-12, 14-16, 19-21, 24, 26, 27, 30, and 32 and canceled claims 4-7, 9, 13, 22, 23, 25, 28, 29, 31, and 33-43.
The amendment received June 23, 2025 changed the status identifiers only.
The amendment received December 1, 2025 amended claims 1, 4, 10, and 12; canceled claims 2 and 3; and added new claim 44.
The amendment received May 27, 2026 amended claims 1, 8, and 10.
Claims 1, 8, 10-12, 14-21, 24, 26, 27, 30, 32, and 44 are currently pending.
Claims 1, 8, 10, 12, and 44 are currently under consideration.
Election/Restrictions
Applicants elected, without traverse, Group I (claims 1-3, 8, 10-12, and 14-16) in the reply filed on June 23, 2025.
Claims 17-21, 24, 26, 27, 30, and 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected methods, there being no allowable generic or linking claim.
Applicants elected, without traverse, 6-12 mg/ml type I collagen, 18-72 mM calcium ions, 0.0125%-0.5% (w/v) riboflavin and blue light, and FBS, hEGF, FGF, and human cells as the species in the reply filed on June 23, 2025.
Claims 11 and 14-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Please note: claim 11 was withdrawn because ionic salts were not elected. Please note: claim 14 is withdrawn because neutralized type I collagen was not elected. Please note: claims 15 and 16 are withdrawn because both sodium and calcium ions were not elected (i.e. see conjunction of “and”).
Applicants contend that claim 11 should be examined. However, applicants do not provide a reasoning based on the elected species as to why claim 11 should be examined. Therefore, claim 11 is still withdrawn.
Priority
The present application is a 371 (National Stage) of PCT/AU2020/051247 filed November 18, 2020 which claims foreign priority to Australia 2019904331 filed November 18, 2019.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Withdrawn Objections
The objection to claim 8 regarding either articles for all members of the Markush group should be present or no articles for the members of the Markush group should be present (see “a culture medium” – lines 2 and 5) is withdrawn in view of the amendment received May 27, 2026.
The rejection of claim 10 regarding “the growth factors comprise” should read “the growth factor(s) comprise(s)” is withdrawn in view of the amendment received May 27, 2026.
The rejection of claim 10 regarding a single conjunction should be present in the Markush group (i.e. delete and/or from lines 3, 4, and 5) is withdrawn in view of the amendment received May 27, 2026.
The objection to claim 8 regarding “amino acids” is duplicated in the claim (see lines 3, 5, and 6) is withdrawn in view of the amendment received May 27, 2026.
Withdrawn Rejections
The rejection of claims 1, 8, 10, 12, and 44 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 is withdrawn in view of the amendment received May 27, 2026.
The rejection of claim 8 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 is withdrawn in view of the amendment received May 27, 2026.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
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, 8, 10, 12, and 44 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. This is a new matter rejection. Support in the originally filed specification was not found for “uncrosslinked type I collagen”. Type I collagen is naturally crosslinked into a triple helical structure. In addition, it is applicants’ responsibility to point out support in the originally filed specification for any amendments.
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, 10, 12, and 44 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. One of skill in the art would not be able to determine the scope of the presently claimed composition. For example, type I collagen is a triple helix (i.e. form of crosslinking) so it is unclear how type I collagen can be uncrosslinked.
Declaration Under 37 CFR § 1.132
The declaration under 37 CFR 1.132 filed May 27, 2026 is insufficient to overcome any rejection of record for any claim as set forth in the last Office action because: the declaration only provides data for riboflavin as a crosslinker. Present independent claim 1 also refers to Rose Bengal as a crosslinker, therefore, the scope of the claims and the scope of the declaration are different (i.e. in addition, the concentration of collagen is different and the sodium or calcium amount is not disclosed which further differentiates the data from the present claims). Furthermore, riboflavin is a known crosslinker for collagen, therefore, the results are not unexpected. See Hatami-Marbini et al., 2018, Effect of UVA/Riboflavin Collagen Crosslinking on Biomechanics of Artificially Swollen Corneas, Cornea (IOVS), 59(2): 764-770; Brennan-Pierce et al., 2014, Riboflavin-sensitized photo-crosslinking of collagen using a dental curing light, Bio-Medical Materials and Engineering, 24: 1659-1671; Heo et al., 2016, Riboflavin-induced photo-crosslinking of collagen hydrogel and its application in meniscus tissue engineering, Drug Deliv and Transl Res, 6: 148-158; and Ahearne et al., 2008, Non-destructive mechanical characterization of UVA/riboflavin crosslinked collagen hydrogels, Br J Ophthalmol, 92: 268-271eo.
Maintained and/or Modified* Rejections
*wherein the modification is necessitated by amendment
Claim Rejections - 35 USC § 102
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.
Claims 1, 8, 10, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Darmoc et al. U.S. Patent Application Publication 2012/0230977 published September 13, 2012.
For present claims 1, 8, 10, and 12, Darmoc et al. teach compositions comprising type I collagen at 10 mg/ml which is further crosslinked (i.e. uncrosslinked initially), calcium ions, Rose Bengal or riboflavin (at ratios of 7.5:1 to 500:1), fibrinogen, Factor XIII, vitamin K, EGF, hormones, antibiotics, and/or mammalian cells including red blood cells and crosslinking via ionic interactions and/or UV photoinitiation (please refer to the entire specification particularly the abstract; paragraphs 4-14, 36, 41, 44, 45, 49, 59-79, 86, 87, 94, 98, 99, 101, 104-106, 108-111, 113-118, 121, 124, 134; claims). The abstract of Darmoc et al. teach “ratio of weight percent collagen solids to weight percent crosslinker”. Paragraph 8 of Darmoc et al. teach “crosslinking about 0.1-10% collagen with a crosslinking agent at a ratio of between 7.5:1 to 500:1”. Paragraph 69 of Darmoc et al. teach that Rose Bengal or riboflavin can be the crosslinkers. Paragraph 72 of Darmoc et al. teach that 10 mg/ml equals 1% of collagen (i.e. therefore, 0.1% collagen would be 1 mg/ml and a ratio of 7.5:1 would be 0.13 mg/ml of crosslinker).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Therefore, the teachings of Darmoc et al. anticipate the presently claimed composition.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102 (a)(1) as being anticipated by Darmoc et al. for claims 1, 8, 10, and 12 were considered but are not persuasive for the following reasons.
Applicants contend that Darmoc et al. do not teach the specific concentration of riboflavin (applicants contend that the ratios are for glutaraldehyde only) or Rose Bengal (applicants contend that the ratios are for glutaraldehyde only).
Applicants’ arguments are not convincing since the teachings of Darmoc et al. anticipate the composition of the instant claims.
The abstract of Darmoc et al. teach “ratio of weight percent collagen solids to weight percent crosslinker”. Paragraph 8 of Darmoc et al. teach “crosslinking about 0.1-10% collagen with a crosslinking agent at a ratio of between 7.5:1 to 500:1”. Paragraph 69 of Darmoc et al. teach that Rose Bengal or riboflavin can be the crosslinkers. Paragraph 72 of Darmoc et al. teach that 10 mg/ml equals 1% of collagen (i.e. therefore, 0.1% collagen would be 1 mg/ml and a ratio of 7.5:1 would be 0.13 mg/ml of crosslinker).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Claims 1, 8, 10, 12, and 44 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Allbritton et al. WO 2018/022548 published February 1, 2018.
For present claims 1, 8, 10, 12, and 44, Allbritton et al. teach compositions comprising type I collagen (0-49 wt %) which is further crosslinked (i.e. uncrosslinked initially), utilizing multiple crosslinkers including ionic bonding with calcium ions and UV crosslinking with riboflavin and addition of human cells, culture medium, growth factors including EGF and FGF, hormones, fibronectin, and matrix proteins (please refer to the entire specification particularly the abstract; pages 2, 3, 9-12, 14-16, 21, 24; claims).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Therefore, the teachings of Allbritton et al. anticipate the presently claimed composition.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102 (a)(1) as being anticipated by Allbritton et al. for claims 1, 8, 10, 12, and 44 were considered but are not persuasive for the following reasons.
Applicants contend that Allbritton et al. do not teach the specific concentration of riboflavin and do not teach Rose Bengal.
Applicants’ arguments are not convincing since the teachings of Allbritton et al. anticipate the composition of the instant claims.
Rose Bengal is optional in present independent claim 1.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
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 1, 8, 10, 12, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Darmoc et al. U.S. Patent Application Publication 2012/0230977 published September 13, 2012; Pang et al., 2017, Unraveling the role of Calcium ions in the mechanical properties of individual collagen fibrils, Scientific Reports, 7: 46042 (8 pages); and McCall et al., 2010, Mechanisms of Corneal Tissue Cross-linking in Response to Treatment with Topical Riboflavin and Long-Wavelength Ultraviolet Radiation (UVA), Investigative Ophthalmology & Visual Science, 51(1): 129-138.
For present claims 1, 8, 10, and 12, Darmoc et al. teach compositions comprising type I collagen at 10 mg/ml which is further crosslinked (i.e. uncrosslinked initially), calcium ions, Rose Bengal or riboflavin, fibrinogen, Factor XIII, vitamin K, EGF, hormones, antibiotics, and/or mammalian cells including red blood cells and crosslinking via ionic interactions and/or UV photoinitiation (please refer to the entire specification particularly the abstract; paragraphs 4-14, 36, 41, 44, 45, 49, 59-79, 86, 87, 94, 98, 99, 101, 104-106, 108-111, 113-118, 121, 124, 134; claims). The abstract of Darmoc et al. teach “ratio of weight percent collagen solids to weight percent crosslinker”. Paragraph 8 of Darmoc et al. teach “crosslinking about 0.1-10% collagen with a crosslinking agent at a ratio of between 7.5:1 to 500:1”. Paragraph 69 of Darmoc et al. teach that Rose Bengal or riboflavin can be the crosslinkers. Paragraph 72 of Darmoc et al. teach that 10 mg/ml equals 1% of collagen (i.e. therefore, 0.1% collagen would be 1 mg/ml and a ratio of 7.5:1 would be 0.13 mg/ml of crosslinker).
For present claims 1, 8, 10, 12, and 44, Pang et al. teach utilizing 10 mM or 20 mM calcium ions for crosslinking collagen (please refer to the entire reference particularly the abstract; Figures 2, 3).
For present claims 1, 8, 10, 12, and 44, McCall et al. teach collagen crosslinking utilizing 0.1% wt/vol riboflavin and utilizing human cells (please refer to the entire reference particularly the abstract; “RFUVA Treatments and Tension Measurements”; Preparation of Riboflavin Solutions).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because the substitution of one known element (i.e. calcium ions; riboflavin) for another (specific concentrations of calcium ions and riboflavin) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. In addition, it is respectfully noted that the prior art may utilize different units than those presently claimed but would still read on the present claims. The claims would have been obvious because a particular known technique (i.e. utilizing a specific concentration of calcium ions or riboflavin to crosslink collagen) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Darmoc et al.; Pang et al.; and McCall et al. for claims 1, 6, 10, 12, and 44 were considered but are not persuasive for the following reasons.
Applicants contend that Darmoc et al. relies on glutaraldehyde. Applicants contend that the cells are merely the in vivo result of applying the material to a bleeding wound. Applicants contend that since Pang et al. only utilized type III collagen, that one of skill in the art would not combine the references. Applicants contend that one of skill in the art would not combine McCall et al. with Darmoc et al. because McCall et al. is drawn to an in vivo composition while the present composition is drawn to an in vitro type I collagen ink.
Applicants’ arguments are not convincing since the teachings of Darmoc et al.; Pang et al.; and McCall et al. render the composition of the instant claims prima facie obvious.
The abstract of Darmoc et al. teach “ratio of weight percent collagen solids to weight percent crosslinker”. Paragraph 8 of Darmoc et al. teach “crosslinking about 0.1-10% collagen with a crosslinking agent at a ratio of between 7.5:1 to 500:1”. Paragraph 69 of Darmoc et al. teach that Rose Bengal or riboflavin can be the crosslinkers. Paragraph 72 of Darmoc et al. teach that 10 mg/ml equals 1% of collagen (i.e. therefore, 0.1% collagen would be 1 mg/ml and a ratio of 7.5:1 would be 0.13 mg/ml of crosslinker). Cells are still taught by Darmoc et al. The composition is not limited to an in vitro composition.
The present composition is not limited to an in vitro composition.
Pang et al. teach that both type I and type II collagen form fibrils from the triple helix structure (i.e. crosslinked structures; see the Introduction on the first page, second paragraph).
McCall et al. teach collagen crosslinking utilizing 0.1% wt/vol riboflavin and utilizing human cells (please refer to the entire reference particularly the abstract; “RFUVA Treatments and Tension Measurements”; Preparation of Riboflavin Solutions).
In response to applicant's argument that Pang et al. and McCall et al. are nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Darmoc et al., Pang et al., and McCall et al. are all drawn to collagen crosslinking.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because the substitution of one known element (i.e. calcium ions; riboflavin) for another (specific concentrations of calcium ions and riboflavin) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. In addition, it is respectfully noted that the prior art may utilize different units than those presently claimed but would still read on the present claims. The claims would have been obvious because a particular known technique (i.e. utilizing a specific concentration of calcium ions or riboflavin to crosslink collagen) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component) and Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998).
Claims 1, 8, 10, 12, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Allbritton et al. WO 2018/022548 published February 1, 2018; Lu et al., 2018, Combined effects of glutaraldehyde and riboflavin/uv365 on the self-assembly of type I collagen molecules observed with atomic force microscopy, International Journal of Food Properties, 21(1): 2181-2192; and Pang et al., 2017, Unraveling the role of Calcium ions in the mechanical properties of individual collagen fibrils, Scientific Reports, 7: 46042 (8 pages).
For present claims 1, 8, 10, 12, and 44, Allbritton et al. teach compositions comprising type I collagen (0-49 wt %) which is further crosslinked (i.e. uncrosslinked initially), utilizing multiple crosslinkers including ionic bonding with calcium ions and UV crosslinking with riboflavin and addition of human cells, culture medium, growth factors including EGF and FGF, hormones, fibronectin, and matrix proteins (please refer to the entire specification particularly the abstract; pages 2, 3, 9-12, 14-16, 21, 24; claims).
For present claims 1, 8, 10, and 12, Lu et al. teach collagen at 4 mg/ml and riboflavin at 0.05%, 0.10%, and 0.20% (w/v) (please refer to the entire reference particularly the abstract; “Preparation of original collagen solutions”, “Preparation of the collagen solutions cross-linked with riboflavin under UV365 irradiation”, Table 1, “Effects of riboflavin/uv365 irradiation on the collagen cross-linking”, Figure 4, “Effects of riboflavin/uv365 irradiation on the mass distribution of collagen molecules”, Figure 5, “Conclusion”).
For present claims 1, 8, 10, and 12, Pang et al. teach utilizing 10 mM or 20 mM calcium ions for crosslinking collagen (please refer to the entire reference particularly the abstract; Figures 2, 3).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because the substitution of one known element (i.e. collagen; calcium ions; riboflavin) for another (specific concentrations of collagen, calcium ions, and riboflavin) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. In addition, it is respectfully noted that the prior art may utilize different units than those presently claimed but would still read on the present claims. The claims would have been obvious because a particular known technique (i.e. utilizing a specific concentration of calcium ions or riboflavin to crosslink a specific concentration of collagen) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Allbritton et al.; Lu et al.; and Pang et al. for claims 1, 8, 10, 12, and 44 were considered but are not persuasive for the following reasons.
Applicants contend that Allbritton et al. do not teach the specific concentration of riboflavin and do not teach Rose Bengal. Applicants contend that the calcium taught in Allbritton et al. is utilized for another purpose. Applicants contend that Lu et al. dilutes the collagen further. Applicants contend that since Pang et al. is drawn to type II collagen that one of skill in the art would not combine the references.
Applicants’ arguments are not convincing since the teachings of Allbritton et al.; Lu et al.; and Pang et al. render the composition of the instant claims prima facie obvious.
Rose Bengal is optional in independent claim 1.
Allbritton et al. teach that calcium ions can also crosslink collagen (i.e. stabilize crosslinking).
While Lu et al. does dilute collagen further, one of skill in the art would recognize that further dilution would not be necessary based on the desired concentration of collagen. One of skill in the art would also recognize that further use of AFM is not necessary.
Pang et al. teach that calcium ions provide benefits to collagen fibrils. Pang et al. teach that both type I and type II collagen form fibrils from the triple helix structure (i.e. crosslinked structures; see the Introduction on the first page, second paragraph).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because the substitution of one known element (i.e. collagen; calcium ions; riboflavin) for another (specific concentrations of collagen, calcium ions, and riboflavin) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. In addition, it is respectfully noted that the prior art may utilize different units than those presently claimed but would still read on the present claims. The claims would have been obvious because a particular known technique (i.e. utilizing a specific concentration of calcium ions or riboflavin to crosslink a specific concentration of collagen) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component) and Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998).
Claims 1, 8, 10, 12, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Patel et al. WO 2016/178586 published November 10, 2016 and Pang et al., 2017, Unraveling the role of Calcium ions in the mechanical properties of individual collagen fibrils, Scientific Reports, 7: 46042 (8 pages).
For present claims 1, 8, 10, 12, and 44, Patel et al. teach compositions comprising type I collagen at a concentration of 3-10 mg/ml, polycationic crosslinkers (e.g. encompassing calcium ions), and UV and 0.1% riboflavin crosslinking wherein growth factors including FGF and EGF, human cells, matrix proteins, anaesthetics, fibronectin, antibiotics, and vitamins may be present (please refer to the entire specification particularly the abstract; paragraphs 15, 22, 24, 30, 35-39, 44, 48, 50, 51, 58-62, 64, 65, 69, 81-88, 96, 102, 121, 128, 134, 141-150, 161-163, 168-170, 184, 195-198, 214, 223, 224, 251, 252, 253, 254, 263, 265).
For present claims 1, 8, 10, 12, and 44, Pang et al. teach utilizing 10 mM or 20 mM calcium ions for crosslinking collagen (please refer to the entire reference particularly the abstract; Figures 2, 3).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because the substitution of one known element (i.e. genus of polycationic crosslinking) for another (calcium ion crosslinking at a specific concentration) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. In addition, it is respectfully noted that the prior art may utilize different units than those presently claimed but would still read on the present claims. The claims would have been obvious because a particular known technique (i.e. utilizing a specific concentration of calcium ions to crosslink collagen) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Patel et al. and Pang et al. for claims 1, 8, 10, 12, and 44 were considered but are not persuasive for the following reasons.
Applicants contend that one of skill in the art would not make a lower concentration collagen solution after reviewing Patel et al. (i.e. higher concentrations of collagen). Applicants contend that Pang et al. only teach type II collagen. Applicants contend that one of skill in the art would not combine the references, that hindsight reasoning was utilized and that there is no motivation. Applicants contend that the declaration shows unexpected results. Applicants contend that hindsight was utilized.
Applicants’ arguments are not convincing since the teachings of Patel et al. and Pang et al. render the composition of the instant claims prima facie obvious.
Patel et al. teach collagen solutions of 3 mg/ml to 10 mg/ml (please refer to the entire specification particularly paragraphs 30, 48, 150).
Pang et al. teach that calcium ions provide benefits to collagen fibrils. Pang et al. teach that both type I and type II collagen form fibrils from the triple helix structure (i.e. crosslinked structures; see the Introduction on the first page, second paragraph).
In response to applicant's argument that Patel et al. and Pang et al. are nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, both Patel et al. and Pang et al. are drawn to collagen crosslinking.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
The claims would have been obvious because the substitution of one known element (i.e. genus of polycationic crosslinking) for another (calcium ion crosslinking at a specific concentration) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. In addition, it is respectfully noted that the prior art may utilize different units than those presently claimed but would still read on the present claims. The claims would have been obvious because a particular known technique (i.e. utilizing a specific concentration of calcium ions to crosslink collagen) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
The declaration filed May 27, 2026 only provides data for riboflavin as a crosslinker. Present independent claim 1 also refers to Rose Bengal as a crosslinker, therefore, the scope of the claims and the scope of the declaration are different (i.e. in addition, the concentration of collagen is different and the sodium or calcium amount is not disclosed which further differentiates the data from the present claims). Furthermore, riboflavin is a known crosslinker for collagen, therefore, the results are not unexpected. Patel et al. teach compositions comprising type I collagen at a concentration of 3-10 mg/ml, polycationic crosslinkers (e.g. encompassing calcium ions), and UV and 0.1% riboflavin (i.e. within the presently claimed range) crosslinking (please refer to the entire specification particularly the abstract; paragraphs 15, 22, 24, 30, 35-39, 44, 48, 50, 51, 58-62, 64, 65, 69, 81-88, 96, 102, 121, 128, 134, 141-150, 161-163, 168-170, 184, 195-198, 214, 223, 224, 251, 252, 253, 254, 263, 265). Also see Hatami-Marbini et al., 2018, Effect of UVA/Riboflavin Collagen Crosslinking on Biomechanics of Artificially Swollen Corneas, Cornea (IOVS), 59(2): 764-770; Brennan-Pierce et al., 2014, Riboflavin-sensitized photo-crosslinking of collagen using a dental curing light, Bio-Medical Materials and Engineering, 24: 1659-1671; Heo et al., 2016, Riboflavin-induced photo-crosslinking of collagen hydrogel and its application in meniscus tissue engineering, Drug Deliv and Transl Res, 6: 148-158; and Ahearne et al., 2008, Non-destructive mechanical characterization of UVA/riboflavin crosslinked collagen hydrogels, Br J Ophthalmol, 92: 268-271eo.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 8, 10, 12, and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6, 13, 14, 16-20, 32, 34, 36, 52, 53, 64-66, 69, and 103 of copending Application No. 18/551,085 (reference application) in view of Patel et al. WO 2016/178586 published November 10, 2016.
Copending Application No. 18/551,085 (reference application) claims compositions comprising type IV collagen at 6-24 mg/ml; one or more crosslinking agents activated by UV light, blue light, green light, or white light including riboflavin at 0.01-0.1 mg; endothelial cells; sodium ions at 0.04-0.15 M; and/or calcium ions at 0.008-0.4 M and also comprising platelet lysate, mammalian cells, culture medium, growth factors including EGF and FGF, hormones, matrix proteins, glycoproteins, vitamins, ions, fibronectin, amino acids, antibiotics, anaesthetics, Factor XIII, FBS, human serum, human platelet lysate, etc.
Patel et al. teach compositions comprising type I collagen at a concentration of 3-10 mg/ml, polycationic crosslinkers (e.g. encompassing calcium ions), and UV and 0.1% riboflavin crosslinking wherein growth factors including FGF and EGF, human cells, matrix proteins, anaesthetics, fibronectin, antibiotics, and vitamins may be present (please refer to the entire specification particularly the abstract; paragraphs 15, 22, 24, 30, 35-39, 44, 48, 50, 51, 58-62, 64, 65, 69, 81-88, 96, 102, 121, 128, 134, 141-150, 161-163, 168-170, 184, 195-198, 214, 223, 224, 251, 252, 253, 254, 263, 265).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because the substitution of one known element (i.e. type IV collagen) for another (type I collagen) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. In addition, it is respectfully noted that the prior art may utilize different units than those presently claimed but would still read on the present claims. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over copending Application No. 18/551,085 (reference application) in view of Patel et al. for claims 1, 8, 10, 12, and 44 were considered but are not persuasive for the following reasons.
Applicants request that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of copending Application No. 18/551,085 (reference application) in view of Patel et al. renders obvious the composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Claims 1, 8, 10, 12, and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 8, 12, 14, 15, 17-21, 24-26, 28, 32, 34, 35, 38, and 50 of copending Application No. 18/550,870 (reference application) in view of Patel et al. WO 2016/178586 published November 10, 2016.
Copending Application No. 18/550,870 (reference application) claims compositions comprising type IV collagen at 6-24 mg/ml; one or more crosslinking agents activated by UV light, blue light, green light, or white light including riboflavin at 0.01-0.1 mg; endothelial cells; sodium ions at 0.04-0.15 M; and/or calcium ions at 0.008-0.4 M and also comprising mammalian cells, culture medium, growth factors including FGF, hormones, matrix proteins, glycoproteins, vitamins, ions, fibronectin, amino acids, antibiotics, anaesthetics, Factor XIII, FBS, human serum, platelet lysate, human platelet lysate, etc.
Patel et al. teach compositions comprising type I collagen at a concentration of 3-10 mg/ml, polycationic crosslinkers (e.g. encompassing calcium ions), and UV and 0.1% riboflavin crosslinking wherein growth factors including FGF and EGF, human cells, matrix proteins, anaesthetics, fibronectin, antibiotics, and vitamins may be present (please refer to the entire specification particularly the abstract; paragraphs 15, 22, 24, 30, 35-39, 44, 48, 50, 51, 58-62, 64, 65, 69, 81-88, 96, 102, 121, 128, 134, 141-150, 161-163, 168-170, 184, 195-198, 214, 223, 224, 251, 252, 253, 254, 263, 265).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because the substitution of one known element (i.e. type IV collagen) for another (type I collagen) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. In addition, it is respectfully noted that the prior art may utilize different units than those presently claimed but would still read on the present claims. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over copending Application No. 18/550,870 (reference application) in view of Patel et al. for claims 1, 8, 10, 12, and 44 were considered but are not persuasive for the following reasons.
Applicants request that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of copending Application No. 18/550,870 (reference application) in view of Patel et al. renders obvious the composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
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/AMBER D STEELE/Primary Examiner, Art Unit 1658
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