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 .
DETAILED ACTION
2. The Examiner of your application in the USPTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to SPE Manjunath Rao.
3. Applicant’s amendment to the claims filed on 04/22/2025 in response to the Non-Final Rejection mailed on 02/10/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
4. Claim 10 is cancelled.
5. Claims 1-9 are pending.
6. Applicant’s remarks filed on 04/22/2025 in response to the Non-Final Rejection mailed on 02/10/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Claim Objections
7. The objections to claims 1, 3, and 6 are withdrawn in view of applicants’ amendments to the claims.
Claim Rejections - 35 USC § 112(b)
8. The rejection of claim 1-10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the relative terms “fresh” and “clean water” is withdrawn in view of applicants’ amendment to the claims to remove the term “clean” and in view of applicants remarks that one of ordinary skill in the art would recognize what the term “fresh” encompasses.
Claim Rejections - 35 USC § 101
9. The rejection of claim 10 under 35 U.S.C. 101 because the claimed invention is directed to a nature-based product without significantly more is withdrawn in view of applicants’ amendment to the claims to cancel claim 10.
Claim Rejections - 35 USC § 102
10. The rejection of claim 10 under 35 U.S.C. 102(a)(1) as being anticipated by Moriyama et al. (US Patent Application Publication US 20130123468 A1, published 05/16/2013, cited in IDS filed on 06/30/2022) is withdrawn in view of applicants’ amendment to the claims to cancel claim 10.
Claim Rejections - 35 USC § 103
11. The rejection of 10 under 35 U.S.C. 103 as being unpatentable over Li et al. (CN Patent Application Publication CN105132502 A, published 09/12/2015, cited in IDS filed on 06/30/2022) in view of Moriyama et al. (US Patent Application Publication US 20130123468 A1, published 05/16/2013, cited in IDS filed on 06/30/2022) and Sturrock et al. (US Patent 5840848, issued 11/24/1998, cited in IDS filed on 06/30/2022) is withdrawn in view of applicants’ amendment to the claims to cancel claim 10.
12. The rejection of claims 1-3 and 6-9 under 35 U.S.C. 103 as being unpatentable over Li et al. (CN Patent Application Publication CN105132502 A, published 09/12/2015, cited in IDS filed on 06/30/2022) in view of Moriyama et al. (US Patent Application Publication US 20130123468 A1, published 05/16/2013, cited in IDS filed on 06/30/2022) and Sturrock et al. (US Patent 5840848, issued 11/24/1998, cited in IDS filed on 06/30/2022) is maintained for the reasons of record and the reasons set forth below.
13. As amended, claims 1-3 and 6-9 are drawn to a method for preparing non-denatured type II collagen, comprising steps successively of:
(1) selecting raw materials from fresh chicken breast cartilage by cutting a part from within 3 cm from a tip of the chicken breast cartilage for use after removing fat and muscle manually;
(2) cleaning the cartilage from step (1) with water at a temperature ≤ 37° C;
(3) draining the cartilage and pulverizing it into particles < 2 mm;
(4) adding water to the cartilage particles from step (3) at a ratio of 0.5 to 3 times the mass of cartilage (m/V); optionally performing beating; adjusting the pH value of feed solution between 2.0 and 4.0; adding pepsin by weight of 1.0-5.0% that of the cartilage, and stirring and hydrolyzing for 0.5 - 2.0 hours at a temperature ≤ 37 °C (optionally 24 – 38.4 °C);
(?) optionally adjusting the pH to 6.8 – 11.4 with lye and allowing to sit for 12 - 72 minutes;
(5)filtering the solution from step (4) with a 20-60 mesh sieve;
(6)vacuum-drying or freeze-drying the materials on the sieve to obtain a dried product;
(7) pulverizing the dried product, sieving through a 60-200-mesh sieve, and taking the materials under the sieve to obtain non-denatured type II collagen powder.
14. Li et al. pertains to a scalable method for extracting pure type II collagen from chicken cartilage that results in high purity type II collagen with high biological activity and stability. (see Li et al. at Abstract, Specification.)
Regarding claim 1, claim 2, claim 8, and steps (1)-(3) of the method, Li et al. teaches the method wherein cartilage is cut from the surface (i.e., the edge) of fresh chicken and separated from non-cartilage components, washed with cold deionized or ultrapure water 3 to 5 times, and mashed into slurry. (see Li et al. at claim 1.1.)
Regarding claim 1, claim 6, claim 7, and step (4) of the method, Li et al. teaches the method wherein the cartilage is washed repeatedly with cold water then uniformly mixed and stirred for 12 - 36 hours, a dilute acetic acid solution (0.4-0.6 mol/L, about 2.48 - 2.57 pH) is added, pepsin is added at a mass fraction of 1-2%, and enzymolysis is carried out, where all steps take place at a temperature of 15 °C or less. (see Li et al. at claim 1.2-1.3, 1.5.)
Regarding claim 10 and a non-denatured type II collagen obtained by the method of claim 1, Li. et al teaches a pure type II collagen extracted from chicken cartilage by a method comprising: pre-processing of cartilage (removing other non-cartilage components from the fresh chicken cartilage surface, washing with normal saline, adding a degreasing agent solution for soaking, washing with cold water for 3-5 times, and taking out and mashing to obtain cartilage slurry), removing soluble protein (a solution H2 of 4 mol/L guanidine hydrochloride in 0.05 mol Perilis-HCl is prepared, the pH is 7.5, added to the precipitate, uniformly mixed and stirred for 12-36 h, centrifugation, and cleaned 3-5 times in cold water), pepsin enzymolysis (adding a dilute acetic acid solution into the solid substance obtained in step 2, mixing uniformly, adding pepsin with a mass fraction of 1-2 wt %, stirring for 24-72 h, centrifuging to obtain a supernatant, and carrying out precipitation and repeated enzymolysis until no precipitate is obtained to obtain a supernatant), and extraction and purification of type II collagen (adjusting the pH of the supernatant obtained in step 3 to 2.5-3.5 with 2 mol/L acetic acid, adding solid NaCl to a final concentration of 3-4.2 mol/L, stirring for 1-2 h, standing overnight, and centrifuging to obtain a precipitate S1; dissolving S1 in dilute acetic acid, adjusting pH to 2.5-3.5, adding solid NaCl to a final concentration of 1.2-2.0 mol/L, stirring for 1-2 h, standing overnight, and centrifuging to obtain precipitate S2, dissolving S2 in dilute acetic acid, adjusting pH to 2.5-3.5, adding solid NaCl to a final concentration of 0.8-1.0 mol/L, stirring for 1-2 h, standing overnight, and centrifuging to obtain precipitate S3; dissolving the precipitate S3 in dilute acetic acid, adjusting the pH to 2.5-3.5, adding solid NaCl to a final concentration of 0.8-1.0 mol/L, and repeating the operation for 2-5 times; and pouring the obtained type II collagen extracting solution into a dialysis bag, and fully dialyzing with 1-5 mmol/L acetic acid to obtain a pure type II collagen). (see Li et al. at claim 1.)
However, Li et al. does not teach the method wherein the enzymatic hydrolysis of step 4 is carried out at 24 – 38.4 °C; the method wherein, following enzymatic hydrolysis, the solution is filtered, vacuum- or freeze-dried and pulverized and sifted to obtain a powder.
Moriyama et al. pertains to a method for extracting water-soluble undenatured type II collagen having an active epitope that allows the epitope to be extracted in large quantities and with high efficiency without any loss of activity. (see Moriyama et al. at Abstract)
Regarding claim 1 and steps (5-7) of the method, Moriyama et al. teaches that when extracting type II collagen via this method, known drying methods such as freeze drying or oven drying can be used following wash steps. When dried at high temperature of 60 °C or above, the type II collagen and the active epitope are potentially denatured, reducing yield. (see Moriyama et al. at Specification, ¶[0032].) Moriyama et al. also discloses that the collagen extracted by the method can be used in the form of a powder obtained by performing centrifugation or filtration followed by oven drying or freeze drying and pulverizing. (see Moriyama et al. at Specification, ¶[0037].)
Sturrock et al. pertains to a method for removing Type I collagen-containing tissue adjoining Type II collagen-containing animal tissue, comprising treatment of unprocessed Type II collagen-containing tissue in an acidic solution in the presence of an acid proteinase, such as pepsin, and subjecting the mixture to moderate agitation for a period of time sufficient to cause digestion or separation of the Type I collagen-containing tissue from the Type II collagen-containing tissue. (see Sturrock et al. at Specification, paragraph 27.)
Regarding claim 3 and optionally adjusting the pH to 6.8 – 11.4 and allowing to sit for 12 - 72 minutes in between steps (4) and (5), Sturrock et al. teaches the method wherein, following pepsin treatment, the pH of the collagen is adjusted to 7-9 by addition of buffer before subsequent steps. (see Sturrock et al. at Specification, paragraph 36).
Regarding claim 9 and the method wherein enzymatic hydrolysis of is carried out at 24 – 38.4 °C, Sturrock et al. teaches that during pepsin treatment of the Type II collagen-containing tissue, the solution can be maintained at about 4 °C – 28 °C. (see Moriyama et al. at Specification, paragraph 34.)
However, the combination of Li et al., Moriyama et al., and Sturrock et al. does not teach the method of claim 1 wherein the size of the cartilage particles is less than 2 mm, the enzymatic hydrolysis step lasts for 0.5 – 2 hours, the hydrolyzed solution is filtered with a 20-60 mesh sieve, and the dried product is sieved through a 60-200 mesh sieve; the method of claim 3 wherein the pH-adjusted solution stands for 12 - 72 minutes before filtering; or the method of claim 8 wherein the cleaning step lasts 10 – 15 minutes per wash.
The parameters of result-effective variables including particle size, mesh sieve size, and the length of pH-adjustment steps and cleaning steps are well described in the above prior art. The accelerated enzymatic hydrolysis step of 0.5 – 2 hours, however, is not described in Li et al, Moriyama et al., or Sturrock et al.
Evidentiary evidence Ali et al. (Process Biochemistry, published 03/2018, cited in PTO-892 as Cite U), which pertains to acid and pepsin soluble collagen extraction from golden carp, teaches that extensive pulverization of cartilage particles affects the potential yield of extracted type II collagen across a range of severable adjustable variables. (see Ali et al. at Abstract, Results.) Specifically, Ali et al. teaches that through pulverization (such as ultrasonification) increases type II collagen yield from the pepsin extraction method across all extraction times, including pepsin extraction times from 0 – 10 hours (see Ali et al. at Figure 1, Figure 2, Results at page 240, col. 1). Evidentiary evidence Akram et al. (Ultrasonics Sonochemistry, published 06/2020, cited in PTO-892 as Cite V) teaches that these ultrasonic pulverization methods are also applicable and beneficial in collagen extraction methods utilizing chicken sternal cartilage (see Akram et al. at Abstract, Results). It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific limitations recited in instant claims 1-3 or claims 6-9 are for any particular purpose or solve any stated problem and the prior art teaches that different pulverization methods and various pepsin hydrolysis extraction times, solutions and parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the art as shown by Ali et al., Akram et al., and the prior art sources cited above.
Therefore, before the effective filing date of the present invention, a person of ordinary skill in the art would be motivated to combine the teachings of Li et al., Moriyama et al., and Sturrock et al. in order to achieve a method for production of type II collagen that is faster, with shorter extraction time, and results in a final product that can be suspended in solution, arriving at the invention of claims 1-3 and 6-9. Said artisan would have a reasonable expectation of success due to the predictable and well-known nature of these steps in the art, as well as the success of said methods reported in the publications of Li et al., Moriyama et al., Sturrock et al., Ali et al., and Akram et al.
15. The rejection of claims 4 and 5 under 35 U.S.C. 103 as being unpatentable over Li et al., Moriyama et al., and Sturrock et al. as applied to claims 1-3 and 6-9 above, and further in view of Manyar et al. (J. Phys. Chem., published 11/20/2008, cited in PTO-892 as Cite W) is maintained for the reasons of record and the reasons set forth below.
The combination of the teachings of Li et al., Moriyama et al., and Sturrock et al. with respect to claims 1-3 and 6-9 as described above does not teach the method of claims 4 and 5, wherein pepsin is added through a load carrier that is food grade silicon dioxide and wherein the pepsin is added to the load carrier at a ratio of 0.24:15 – 0.72:15.
Manyar et al. pertains to synthesis and characterization of a bioreactor made via physical adsorption of pepsin within a mesoporous silica system. (see Manyar et al. at Abstract, Introduction).
Regarding claim 4 and the method wherein pepsin is added through a load carrier that is food grade silicon dioxide, Manyar et al. teaches that in the art of biochemical engineering, enzymes are often immobilized on solid supports such as ordered porous solids in order to reduce autolysis and protein aggregation, and to enable highly selective catalysis with hybrid materials that are readily separated from reaction mixtures (see Manyar et al. at Introduction). More specifically, Manyar et al. teaches that pepsin can be immobilized using mesoporous silica while retaining its catalytic activity and allowing for reuse of the immobilized pepsin.
Regarding claim 5 and the method wherein pepsin is added to the load carrier at a ratio of 0.24:15 – 0.72:15, Manyar et al. teaches the loading of pepsin onto SBA-15 mesoporous silica at ratios of 50 mg of SBA-15 to 0.5-2.0 mg/mL of pepsin. (see Manyar et al. at page 2, column 1, section 2.3.) Furthermore, determination of desired addition ratios would be reached by a skilled artisan in the process of routine optimization as described in the rejection above.
Therefore, before the effective filing date of the present invention, a person of ordinary skill in the art would be motivated to combine the teachings of Li et al., Moriyama et al., and Sturrock et al. with the teachings of Manyar et al. in order to achieve a method for production of type II collagen that is more catalytically efficient during the enzymatic hydrolysis step, reducing autolysis of pepsin and enabling reuse of the immobilized pepsin and thereby decreasing costs of operating the method, arriving at the invention of claims 4 and 5. Said artisan would have a reasonable expectation of success due to the predictable and well-known nature of silica-based enzyme immobilization in the art, as well as the success of said methods reported by Manyar et al.
Response to Remarks Regarding Prior Art Rejections
16. Beginning on p. 5 of applicants’ remarks, applicants in summary contend that the distinguishing features of the claimed invention is how to obtain non-denatured Type II collagen with high content, volume expansion ratio and water absorption ratio. Applicants contend that the prior art does not disclose or appreciate that the content, volume expansion ratio and water absorption ratio of undenatured type II collagen are different in different cartilages and different parts of the same cartilage.
These arguments are found to be not persuasive because MPEP 2145.II states “[m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979) (Claims were directed to grooved carbon disc brakes wherein the grooves were provided to vent steam or vapor during a braking action. A prior art reference taught noncarbon disc brakes which were grooved for the purpose of cooling the faces of the braking members and eliminating dust. The court held the prior art references when combined would overcome the problems of dust and overheating solved by the prior art and would inherently overcome the steam or vapor cause of the problem relied upon for patentability by applicants. Granting a patent on the discovery of an unknown but inherent function (here venting steam or vapor) "would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art." 596 F.2d at 1022, 201 USPQ at 661.); In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991) (Appellant argued that the presence of DEHP as the plasticizer in a blood collection bag unexpectedly suppressed hemolysis and therefore rebutted any prima facie showing of obviousness. However, the closest prior art utilizing a DEHP plasticized blood collection bag inherently achieved same result, although this fact was unknown in the prior art.). "The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").” In the instant case, Li et al. already discloses separation of chicken cartilage from the edges (which can be interpreted as “within 3 cm from a tip). As such, it is the examiner’s position that the features of volume expansion ratio and water absorption ratio of undenatured type II collagen would be a latent property that flows from the teachings set forth by the combination of Li et al., Moriyama et al., and Sturrock et al.
Conclusion
17. Status of the claims:
Claims 1-9 are pending.
Claims 1-9 are rejected.
No claims are in condition for an allowance.
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 MANJUNATH RAO whose telephone number is (571)272-0939. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM. 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:/Avwww.uspto.gov/interview practice. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, DAN SULLIVAN (Director TC 1600) can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571 - 273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https:/Awww.uspto.gov/patents/apply/patent- center for more information about Patent Center and https:/Awww.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MANJUNATH N RAO/ Supervisory Patent Examiner, Art Unit 1656
Prosecution Insights