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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 October 30, 2025 has been entered.
Election/Restrictions
Applicant elected without traverse of Group V (claims 7-8) in the reply filed on October 31, 2024.
Claims 1-6 and 10-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 31, 2024.
Claim 9 has been rejoined.
Status of Claims
Claims 1-21 are pending.
Claims 1-6 and 10-21 are withdrawn.
Claims 7-9 are under examination.
Declaration under 37 § C.F.R. 1.132
The declaration under 37 CFR 1.132 filed October 30, 2025 is insufficient to overcome the rejection of claims 7-8 based upon Zotzel (Activated transglutaminase from Streptomyces mobaraensis is processed by a tripeptidyl aminopeptidase in the final step. Eur J Biochem. 2003 Oct;270(20):4149-55. – form PTO-1449), Jensen (WO 93/15234 – form PTO-1449), and Hua (US 2009/0004720 – form PTO-892) as set forth in the last Office action because:
MPEP 716.02 (d) states that “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 the instant application, Example 8 and paragraphs [00144] and [00145] are limited to co-immobilized Streptomyces mobaraensi TAMEP and Streptomyces mobaraensis TAP, wherein activation of Streptomyces mobaraensi Tgase by said co-immobized TAMEP and TAP results in higher transglutaminase activity compared to activation of immobilized TAMEP and TAP separately. However, claims 7-8 are directed to any microbial or any Streptomyces sp. TAMEP and any microbial or any Streptomyces sp. TAP. Therefore, Example 8, paragraphs [00144] and [00145], and the Declaration are insufficient to rebut the prima facie case because the alleged unexpected results are not commensurate in scope with the claims.
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 7-8 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is noted that MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' The claims have been broadly interpreted to encompass any microbial or any Streptomyces sp. transglutaminase M4 metalloprotease (TAMEP) and any microbial or any Streptomyces sp. tripeptidyl aminopeptidase (TAP) co-immobilized on a porous solid support, wherein higher transglutaminase activity is achieved when a microbial transglutaminase or variant thereof is activated by using the co-immobilized microbial/Streptomyces sp. TAMEP and microbial/Streptomyces sp. TAP compared to using the microbial/Streptomyces sp. TAMEP and the microbial/Streptomyces sp. TAP separately immobilized on the porous solid support. Therefore, the claims are drawn to a genus of microbial/Streptomyces sp. TAMEP and microbial/Streptomyces sp. TAP co-immobilized on a porous solid support, wherein higher transglutaminase activity is achieved when a microbial transglutaminase or variant thereof is activated by using the genus of co-immobilized microbial/Streptomyces sp. TAMEP and microbial/Streptomyces sp. TAP compared to using the microbial/Streptomyces sp. TAMEP and the microbial/Streptomyces sp. TAP separately immobilized on the porous solid support
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) sates that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The recitation of “higher transglutaminase activity is achieved” fails to provide a sufficient description of the genus of co-immobilized microbial/Streptomyces sp. TAMEP and microbial/Streptomyces sp. TAP as it merely describes the functional features of the genus without providing any definition of the structural features of the species within the genus. The specification does not specifically define any of the species that fall within the genus. The specification does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus.
The prior art discloses that Streptomyces mobaraensis transglutaminase (TGase) is secreted as a precursor, which is activated by secreted Streptomyces mobaraensis TAMEP and secreted Streptomyces mobaraensis TAP in a single step, see Zotzel (Activated transglutaminase from Streptomyces mobaraensis is processed by a tripeptidyl aminopeptidase in the final step. Eur J Biochem. 2003 Oct;270(20):4149-55. – form PTO-1449, abstract). However, transglutaminase having higher transglutaminase activity when activated by any microbial or any Streptomyces sp. TAMEP co-immobilized with any microbial or any Streptomyces sp. TAP compared to using the microbial/Streptomyces sp. TAMEP and the microbial/Streptomyces sp. TAP separately immobilized on the porous solid support was not known in the art.
The specification is limited to a Streptomyces mobaraensis TAMEP and a Streptomyces mobaraensis TAP co-immobilized on a porous solid support, wherein a transglutaminase has higher transglutaminase activity when activated by co-immobilized Streptomyces mobaraensis TAMEP and a Streptomyces mobaraensis TAP compared to using the Streptomyces mobaraensis TAMEP and a Streptomyces mobaraensis TAP separately immobilized on the porous solid support. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the widely variant species encompassed by the genus, the examples described above is not enough and does not constitute a representative number of species to describe the whole genus. Therefore, the specification fails to describe a representative species of the claimed genus.
The claimed invention requires a defined set of TAMEP and TAP. Although the specification discloses exemplary TAMEP and TAP, a “laundry list” disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species, see Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) or MPEP 2163. While the exemplary TAMEP and TAP were known in the art, this knowledge alone would not allow one level of skill in the art to immediately envisage the claimed genus, wherein a transglutaminase has higher transglutaminase activity when activated with any microbial or any Streptomyces sp. TAMEP and any microbial or any Streptomyces sp. TAP compared to using the microbial or Streptomyces sp. TAMEP and microbial or Streptomyces sp. TAP separately immobilized on the porous solid support. Therefore, the level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which combination of TAMEP and TAP to use to arrive at the claimed invention.
Given this lack of description of the representative species encompassed by the genus of the claims, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the inventions of claims 7-8.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 7 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zotzel (Activated transglutaminase from Streptomyces mobaraensis is processed by a tripeptidyl aminopeptidase in the final step. Eur J Biochem. 2003 Oct;270(20):4149-55. – form PTO-1449), Jensen (WO 93/15234 – form PTO-1449), and Hua (US 2009/0004720 – form PTO-892).
Regarding the limitation “porous solid support”, paragraph [0073] provides examples of porous solid support, such as polystyrene
Regarding claim 7, Zotzel discloses that Streptomyces mobaraensis transglutaminase (TGase) is secreted as a precursor, which is activated by secreted Streptomyces mobaraensis TAMEP and secreted Streptomyces mobaraensis TAP in a single step (abstract). Zotzel discloses purification of said TGase, TAMEP and TAP (page 4150 “Materials” and “Purification of the tripeptide amino peptides from S. mobaraensis (SM-TAP)”).
Zotzel does not disclose co-immobilizing the TAMEP and TAP on a porous solid support.
Jensen discloses activating a transglutaminase precursor with an immobilized proteolytic enzyme on a porous solid support, such as polystyrene (abstract, page 4 line 26 through page 5 line 4, and page 5 line 27 through page 6, line 14). The instant specification at paragraph
Use of immobilized enzymes for catalysis was known in the art to provide ease of recovery and/or reuse, simply downstream processing, ease adaptation for continuous operation, and/or improve one or more properties of the enzyme, see Hua [0010]).
Regarding the property recited in clam 7, MPEP 2145 II states that " Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention…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." In the instant application, Zotzel discloses that Streptomyces mobaraensis TAMEP and Streptomyces mobaraensis TAP activates Streptomyces mobaraensis transglutaminase (TGase) in a single step. Jensen discloses activating a transglutaminase precursor with an immobilized proteolytic enzyme on a porous solid support, such as polystyrene. The specification of the instant application discloses a Streptomyces mobaraensis TAMEP and a Streptomyces mobaraensis TAP co-immobilized on a porous solid support, wherein a transglutaminase has higher transglutaminase activity when activated by said co-immobilized Streptomyces mobaraensis TAMEP and a Streptomyces mobaraensis TAP compared to using the Streptomyces mobaraensis TAMEP and a Streptomyces mobaraensis TAP separately immobilized on the porous solid support (Example 8, Table 4, and FIG. 2.). Therefore, the property of having higher transglutaminase activity when a Streptomyces mobaraensis transglutaminase is activated by co-immobilized Streptomyces mobaraensis TAMEP and Streptomyces mobaraensis TAP compared to using the Streptomyces mobaraensis TAMEP and the Streptomyces mobaraensis TAP separately immobilized on the porous solid support would flow naturally from following the suggestion of the citied references under normal and usual operation.
Therefore, in combining the teachings Zotzel, Jensen, and Hua, it would have been obvious to one having ordinary skill in the art before the time the claimed invention was effectively filed to co-immobilize the TAMEP and TAP in order to activate the TGase. One having ordinary skill in the art would have been motivated to do so because immobilization of enzymes simplifies downstream processing and allows for reuse of TAMEP and TAP and allows for simplified recovery of TGase and TAMEP-TAP and TAMEP and TAP activates TGase in a single step. One having ordinary skill in the art would have had a reasonable expectation of success since Zotzel discloses S. mobaraensis TAMEP and S. mobaraensis TAP that activates S. mobaraensi TGase, Jensen discloses immobilization of a proteolytic enzyme for activation of a transglutaminase, and advantages of immobilizing of enzymes for catalysis was known in the art, as disclosed by Hua. Using the known technique of immobilization of a proteolytic enzyme for activation of a transglutaminase would have been obvious to one of ordinary skill. The rationale supporting that the claims would have been obvious is that a method of enhancing a particular class of devices (activating a transglutaminase with an immobilized proteolytic enzyme) has been made part of the ordinary capabilities of one skilled in the art based upon the teaching of such improvement in other situations. One of ordinary skill in the art would have been capable of applying this known method of enhancement to a “base” device (activating S. mobaraensi transglutaminase with S. mobaraensi TAMEP and S. mobaraensis TAP) in the prior art and the results would have been predictable to one of ordinary skill in the art.
Therefore, the above references render claims 7 and 9 prima facie obvious.
Applicant's arguments filed October 30, 2025 have been fully considered but they are not persuasive.
Applicant argues that the amended claims are not obvious because there was no reasonable expectation of success because (1) as described in the Declaration under 37 CFR 1.132 and Example 8, increased transglutaminase activity is achieved by using a combination of TAMEP and TAP with higher total protease activity, (2) none of the cited references teaches or suggests that use of co-immobilization of TAMEP and TAP to activate a transglutaminase results in higher transglutaminase activity compared to using immobilized TAMPE and TAP separately, and (3) Hua teaches that co-immobilized enzymes have similar activity and similar stability.
This is not found persuasive.
MPEP 2145 II states that " Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention…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." In the instant application, Zotzel discloses that Streptomyces mobaraensis TAMEP and Streptomyces mobaraensis TAP activates Streptomyces mobaraensis transglutaminase (TGase) in a single step. Jensen discloses activating a transglutaminase precursor with an immobilized proteolytic enzyme on a porous solid support, such as polystyrene. The specification of the instant application discloses a Streptomyces mobaraensis TAMEP and a Streptomyces mobaraensis TAP co-immobilized on a porous solid support, wherein a transglutaminase has higher transglutaminase activity when activated by said co-immobilized Streptomyces mobaraensis TAMEP and a Streptomyces mobaraensis TAP compared to using the Streptomyces mobaraensis TAMEP and a Streptomyces mobaraensis TAP separately immobilized on the porous solid support (Example 8, Table 4, and FIG. 2.). Therefore, the property of having higher transglutaminase activity when a Streptomyces mobaraensis transglutaminase is activated by co-immobilized Streptomyces mobaraensis TAMEP and Streptomyces mobaraensis TAP compared to using the Streptomyces mobaraensis TAMEP and the Streptomyces mobaraensis TAP separately immobilized on the porous solid support would flow naturally from following the suggestion of the citied references under normal and usual operation.
Applicant argues that the amended claims are not obvious because of the unexpected results of co-immobilized microbial TAMPE and microbial TAP having higher total protease activity compared to a combination of individually immobilized microbial TAMEP and microbial TAP for transglutaminase activation and one having ordinary skill in the art would not have expected
This is not found persuasive.
MPEP 716.02 (d) states that “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 the instant application, Example 8 and paragraphs [00144] and [00145] are limited to co-immobilized Streptomyces mobaraensi TAMEP and Streptomyces mobaraensis TAP, wherein activation of Streptomyces mobaraensi Tgase by said co-immobized TAMEP and TAP results in higher transglutaminase activity compared to activation of immobilized TAMEP and TAP separately. However, claim 7 is directed to any microbial or any Streptomyces sp. TAMEP and any microbial or any Streptomyces sp. TAP. Therefore, Example 8, paragraphs [00144] and [00145], and the Declaration are insufficient to rebut the prima facie case because the alleged unexpected results are not commensurate in scope with the claims.
Hence the rejection is maintained.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zotzel (Activated transglutaminase from Streptomyces mobaraensis is processed by a tripeptidyl aminopeptidase in the final step. Eur J Biochem. 2003 Oct;270(20):4149-55. – form PTO-1449), Jensen (WO 93/15234 – form PTO-1449), and Hua (US 2009/0004720 – form PTO-892) as applied to claim 7 above, and further in view of A0A3G4VZ98_9ACTN (UniProtKB/TrEMBL. April 7, 2021. – form PTO-892) and
A0A3G4VPC7_9ACTN (UniProtKB/TrEMBL. April 7, 2021. – form PTO-892).
The combined teachings of Zotzel, Jensen, and Hua do not disclose a Streptomyces sp. TAMEP and Streptomyces sp. TAP.
However, both enzymes were known in the art, as discussed below.
A0A3G4VZ98_9ACTN discloses Streptomyces sp. TAMEP (pages 1-2) and A0A3G4VPC7_9ACTN discloses Streptomyces sp. TAP (pages 1-2).
Therefore, in combining the above teachings, it would have been obvious to one having ordinary skill in the art before the time the claimed invention was effectively filed to co-immobilize the Streptomyces sp. TAMEP of A0A3G4VZ98_9ACTN and Streptomyces sp. TAP of A0A3G4VPC7_9ACTN. One having ordinary skill in the art would have been motivated to do so in order to activate Streptomyces sp. transglutaminases. One having ordinary skill in the art would have had a reasonable expectation of success since Zotzel discloses S. mobaraensis TAMEP and TAP that activates S. mobaraensi transglutaminase, Jensen discloses immobilization of a proteolytic enzyme for activation of a transglutaminase, advantages of immobilizing of enzymes for catalysis was known in the art, as disclosed by Hua, A0A3G4VZ98_9ACTN discloses Streptomyces sp. TAMEP, and A0A3G4VPC7_9ACTN discloses Streptomyces sp. TAP. Using the known technique of immobilization of a proteolytic enzyme for activation of a transglutaminase would have been obvious to one of ordinary skill. The rationale supporting that the claims would have been obvious is that a method of enhancing a particular class of devices (activating a transglutaminase with an immobilized proteolytic enzyme) has been made part of the ordinary capabilities of one skilled in the art based upon the teaching of such improvement in other situations. One of ordinary skill in the art would have been capable of applying this known method of enhancement to a “base” device (activating Streptomyces sp. transglutaminase with Streptomyces sp. TAMEP and Streptomyces sp. TAP) in the prior art and the results would have been predictable to one of ordinary skill in the art.
Therefore, the above references render claims 7-8 prima facie obvious.
Applicant argues that amended claims 7-8 is not obvious over the cited references for the reasons stated above.
Applicant’s arguments were not found persuasive as discussed above. Hence the rejection is maintained.
Conclusion
Claims 1-21 are pending.
Claims 1-6 and 10-21 are withdrawn.
Claims 7-9 are rejected.
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/YONG D PAK/Primary Examiner, Art Unit 1652