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 .
Priority
This application filed 11/24/2023 is a National Stage entry of PCT/CN2022/092370 ,International Filing Date: 05/12/2022, claims foreign priority to 202110547279.5, filed 05/19/2021 claims foreign priority to 202210491708.6, filed 05/01/2022.
Information Disclosure Statement
No IDS has been submitted.
Status of claims
The amendments and arguments filed on 07/19/2026 are acknowledged and have been fully
considered. Claims 2, 14 and 28 are amended, claims 1, 3-13, 15, 18, 20 and 23 are canceled. Claims 2, 14, 16-17, 19, 21, 22, 24-28 are now pending and will be examined on the merits herein.
Objections/Rejections Withdrawn
Objections and/or rejections not reiterated from previous Office Action are hereby withdrawn.
The following rejections and/or objections are either reiterated or newly applied, and constitute the
complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 14, 16, 17, 19, 21-22, 24-28 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 recites ‘a concentration of the fibrinogen’ (line 7), ‘a concentration of the fibrin’ (line 8), ‘a concentration of the thrombin’ (line 9), ‘a concentration of calcium’ (line 11), ‘a concentration of plasminogen’ (line 13). Here, because the claim recites the article ‘a’, it is unclear whether Applicant intends the recited concentrations to be one of several possible concentrations. As a result, ambiguity arises. For prior art purposes, Examiner interprets the recited concentration ranges as referring to the ranges present in the composition gel and not interpreted as one of many possible ranges.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 2, 14, 16, 17, 19, 21, 22, 24-28 are rejected under 35 U.S.C. 103 as being unpatentable over Hisahiro Yoshida et al., hereinafter Yoshida (Hisahiro Yoshida et al., Biol. Pharm. Bull. 22(11) 1222-1225(1999)) in view of Jean-Marie Vogel et al., hereinafter Vogel (WO2008/042756; published 10 April 2008; EFD: 29 September 2006) evidenced by L, Lorand et al., hereinafter Lorand (L, Lorand et al., J Clin Invest. 1969 Jun; 48(6): 1054-64).
Regarding claim 2, Yoshida teaches fibrin glue. Fibrin glue consists of fibrinogen (i.e. component A), factor XIII (F-XIII) (i.e. component A), thrombin (i.e. component B), CaCl2, and aprotinin. Yoshida teaches that fibrin glue products are commercially available and widely used (see Introduction 1st paragraph). Regarding the claim limitation “fibrin stabilizing factor”, embodiments of the specification do not disclose “fibrin stabilizing factor”. Under a broadest reasonable interpretation (BRI), words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989) (discussed below); Chef America, Inc. v. Lamb-Weston, Inc., 358 F.3d 1371, 1372, 69 USPQ2d 1857 (Fed. Cir. 2004). The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a “fibrin stabilizing factor” in the art, before the effectively filed date of the claimed invention, is “Factor XIII” as evidenced by Lorand (see Abstract). Yoshida teaches fibrinogen concentration in the centrifugation method is approximately 1 mg/ml (see Fig 1) and F-XIII is 0.5 mg/ml (i.e., 1.8 to 3.8 mg/ml); thrombin 100 units/ml (see Lysing Test of Fibrin Glue) and CaCl2 (0.2%).
Yoshida does not teach the specific concentrations as claimed.
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. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). 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). "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." (see MPEP 2144.05 II(A)). Therefore, the teachings of Yoshida, by routine optimization, would have yielded predictable results and the concentration of the claimed composition. One motivated to do so would have a reasonable expectation of success as Yoshida specifically teaches the components of the composition.
Regarding claims 14, in Fig 4, Yoshida teaches plasminogen yields from three different methods for generation of fibrinogen-rich-fraction (FRF), which range from 1-2 units/ml or 7-10 % yield i.e. corresponding to 00083 mg/ml to 0.016 mg/ml (specific activity approx. 120 units/ mg protein).
Yoshida does not teach 0.031 mg/ml plasminogen.
As noted above, 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. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). 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).
Regarding claims 16, 17, 19, Yoshida does not teach a coloring agent wherein the coloring agent is methylene blue, chlorophyll or indocyanine green.
Vogel teaches polymer composition to remove biological concretions, such as urinary, biliary, and pancreatic stones within the body’s anatomical lumen (page 5, line 18) to prevent retropulsion of fragments during lithotripsy (page 4, line 21). Vogel teaches polymer composition that comprise fibrinogen, fibrin (page 13, line 20) and crosslinking agent e.g., calcium (page 14, line 4). Notably, Vogel teaches the composition comprising contrast-enhancing agent (page 16, line 10) (i.e. coloring agent). Vogel teaches that the contrast-enhancing agent is selected from the group consisting of dyes (page 16, line 16). In Example 2, Vogel specifically teaches that prior to injection, the composition may be made visible by addition of methylene blue (page 18, line 26; Example 4, line 22).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re
Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Yoshida and introduce a contrast-enhancing agent as suggested in Vogel. One motivated to do so would have a reasonable expectation of success as the composition is directed to the removal of kidney stone by surgery and Vogel specifically teaches that “contrast-enhancing agents” are capable of being monitored during injection into a mammalian subject (See page 6, line 9). Notably, Vogel teaches that methylene blue is used to enhance visualization (see page 19, line 23). Therefore, one would have recognized that applying the teaching of Vogel to the teachings of Yoshida would have yielded predictable results and enhanced visualization of the composition for detection (See MPEP § 2143 I(A)(D)).
Regarding claim 21, the teachings of Vogel and Yoshida have been set forth above. 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. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). 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). "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." (see MPEP 2144.05 II(A)). Therefore, combining the teachings of Yoshida and Vogel by routine optimization would have yielded the concentration of methylene blue in the claimed composition. One motivated to do so would have a reasonable expectation of success as Vogel specifically teaches use of methylene blue as a contrast enhancing agent in the composition.
Regarding claim 22, Yoshida specifically teaches preparation of FRF from human plasma (i.e. human blood) (see materials and methods, page 1). In Fig 4, Yoshida teaches plasminogen yields from three different methods for generation of fibrinogen-rich-fraction (FRF), which range from 1-2 units/ml or 7-10 % yield i.e. corresponding to 00083 mg/ml to 0.016 mg/ml (specific activity approx. 120 units/ mg protein).
Yoshida does not teach a coloring agent.
Vogel teaches polymer composition to remove biological concretions, such as urinary, biliary, and pancreatic stones within the body’s anatomical lumen (page 5, line 18) to prevent retropulsion of fragments during lithotripsy (page 4, line 21). Notably, Vogel teaches the composition comprising contrast-enhancing agent (page 16, line 10) (i.e. coloring agent). Vogel teaches that the contrast-enhancing agent is selected from the group consisting of dyes (page 16, line 16).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re
Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the
effective filing date of the claimed invention to modify the composition of Yoshida and introduce a contrast-enhancing agent as suggested in Vogel. One motivated to do so would have a reasonable expectation of success as Vogel specifically teaches that “contrast-enhancing agents” are capable of being monitored during injection into a mammalian subject by methods for monitoring and detecting such materials (See page 6, line 9). Notably, Vogel teaches that methylene blue can be used to enhance visualization (see page 19, line 23). Therefore, one would have recognized that applying the teaching of Vogel to the teachings of Yoshida would have yielded predictable results and enhanced visualization of the composition for detection (See MPEP § 2143 I(A)(D)).
Regarding claim 24, Vogel teaches saline irrigation to effectively dissolve polymer plugs (see Example 4; page 20 line 6; page 20 line 27). Vogel suggests that for preventing the migration of a concretion, or its fragments, during extracorporeal or intracorporeal lithotripsy, the lumen is cleared by rinsing with saline (see page 5, line 25). Therefore, combining the teachings of Yoshida and contacting the composition with saline irrigation of polymer plugs as suggested in Vogel, would have yielded predictable results as Vogel teaches preventing retropulsion of fragments during lithotripsy. One motivated to do so would have a reasonable expectation of success as Vogel specifically teaches that saline irrigation effectively dissolves polymer plugs and prevents the migration of a concretion or its fragments (page 5, line 22).
Regarding claims 25, 26 and 27, Yoshida specifically teaches preparation of FRF from human plasma (i.e. human blood); i.e. fibrinogen and fibrin stabilizing factor (see materials and methods, page 1). Yoshida does not teach saline.
As noted above, Vogel teaches saline irrigation to effectively dissolve polymer plugs (see Example 4; page 20 line 6; page 20 line 27). Vogel suggests that for preventing the migration of a concretion, or its fragments, during extracorporeal or intracorporeal lithotripsy, the lumen is cleared by rinsing with saline (see page 5, line 25). Therefore, combining the teachings of Yoshida and contacting the composition with saline irrigation of polymer plugs as suggested in Vogel, would have yielded predictable results as Vogel teaches preventing retropulsion of fragments during lithotripsy. One motivated to do so would have a reasonable expectation of success as Vogel specifically teaches that saline irrigation effectively dissolves polymer plugs and prevents the migration of a concretion or its fragments.
Regarding claim 28, Yoshida teaches fibrinogen concentration in the centrifugation method is approximately 1 mg/ml (see Fig 1) and F-XIII is 0.5 mg/ml (i.e., 1.8 to 3.8 mg/ml); thrombin 100 units/ml (see Lysing Test of Fibrin Glue) and CaCl2 (0.2%).
Yoshida does not teach the specific concentrations as claimed.
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. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). 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). "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." (see MPEP 2144.05 II(A)). Therefore, the teachings of Yoshida, by routine optimization, would have yielded predictable results and the concentration of the claimed composition. One motivated to do so would have a reasonable expectation of success as Yoshida specifically teaches the components of the composition.
Response to Arguments
Applicant's arguments filed 07/19/2026 have been fully considered but they are not persuasive.
Applicant argues that Yoshida, Vogel and Lorand fail to teach the ranges of concentrations. Therefore, the instant invention is not the same as disclosed in the prior art. 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. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). 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). "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." (see MPEP 2144.05 II(A)). In the instant case, the teachings of Vogel disclose polymer compositions comprising fibrinogen, fibrin and calcium (page 13, line 20; page 14, line 4) to remove biological concretions such as urinary stones within the body’s anatomical lumen (page 5, line 18). Therefore, combining the teachings in Vogel and Yoshida, by routine optimization, it would be obvious to generate the claimed ranges in the composition, for the purpose of removing residual stone fragments after lithotripsy. One motivated to do so would have a reasonable expectation of success as the teachings in Vogel is directed to the same inventive concept as the instant application.
Applicant argues that the combination of Yoshida, Vogel and Lorand is not obvious and relies on hindsight reasoning. 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). One motivated to combine Yoshida and Vogel, would have a reasonable expectation of success as Yoshida teaches the components of the claimed composition and Vogel teaches polymer composition specifically, to remove biological concretions, such as urinary, biliary, and pancreatic stones within the body’s anatomical lumen (page 5, line 18) to prevent retropulsion of fragments during lithotripsy (page 4, line 21). Polymer compositions disclosed in Vogel, comprise fibrinogen, fibrin (page 13, line 20) and crosslinking agent e.g., calcium (page 14, line 4). In Example 2, Vogel specifically teaches that prior to injection, the composition may be made visible by addition of methylene blue (page 18, line 26; Example 4, line 22).
Applicant argues, unexpected results in currently amended claims 2, 14, 16, 17, 19, 21, 22, 24-28 and the criticality of the concentrations, evident in Fig 1C-1E. Please note that the Figures are in greyscale, and the Examiner is unable to observe the gel wrapping around stone fragments, the presence of fragments or the removal of fragments as stated in the arguments by Applicant. Here, the Examiner would like to remind the Applicant that the burden is on the Applicant to establish results are unexpected and significant. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). “[E]evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977). Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof."
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARCHANA VARADARAJ whose telephone number is (571)272-2366. The examiner can normally be reached Monday-Friday 10:00am-5:00pm.
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/ARCHANA VARADARAJ/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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