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 .
Status of the application
Receipt of applicant’s remarks and claim amendments filed on 09/25/2025 are acknowledged.
In light of claim amendments, previous 102 rejection is withdrawn
However, applicants’ arguments for the previous 103 rejection are found not persuasive. Accordingly, the previous rejection is maintained and modified to address claim amendments. Please see the examiners response to applicants arguments below.
Response to Arguments
Applicants’ argue that Bolyard nor Osther teaches or suggests the specific polypeptide as claimed, which has advantageously and unexpectedly characterized in that it adopts a functionally active conformation, in a spontaneous manner, e.g., after a buffer change from a buffer containing high amounts of chaotropic agents, or even directly out of a respective solution containing high amounts of chaotropic agents. In addition, inclusion bodies (IBs) of the polypeptide can be used directly, e.g., to coat plates, without solubilization. This is particularly surprising since the fibrinogen gamma chain on its own, i.e., in the absence of the other fibrinogen chains (i.e., alpha and beta chains), does not have a natural conformation. Nevertheless, polypeptides as claimed can spontaneously adopt a conformation in which they are not distinguishable from native fibrinogen, e.g., when used as a cell culture plate coating.
Advantage of His-tag is that the coupled protein retains its property in its conjugate form with His-tag and also even after His-tag is cleaved off from the conjugate. That is the advantage of His-tag chemistry in the protein purification technology. It is not clear what kind of unexpected property, the claimed conjugate shows, either from the claim language or from the specification. There is no comparative data shown. It appears that applicants arguments are mere statements.
Unexpected results must be established by factual evidence. Mere argument or conclusory statements in the specification does not suffice. In re Lindner, 457 F.2d 506, 508 (CCPA 1972). "[W]hen unexpected results are used as evidence of nonobviousness, the results must be shown to be unexpected compared with the closest prior art." In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).
Applicants further argue that neither Gaberc-Porekar nor Kambadur remedy the deficiencies of Bolyard and Osther. In particular, neither Gaberc-Porekar nor Kambadur, taken alone or in combination with each other, teaches or suggests the specific polypeptide as claimed, much less any of its advantageous properties.
The purpose of Gaberc-Porekar is to show the advantages of His-tag in protein purification, whereas the purpose of Kambadur is to show the sequence of His-tag.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Bolyard (Gene, 1988, 66, 183-192; see applicants filed IDS dated 02/07/2023) or Osther (WO 2014/115087 A2) in view of Gaberc-Porekar (Chem.Eng.Technol., 2005, 28, No.11, 1306-1314) and Kambadur (US 2009/0324590 A1).
For claim 1:
Bolyard teaches gamma chain of fibrinogen [see abstract and Fig.1].
or
Osther teaches gamma chain of fibrinogen [see SEQ ID NO:11 in page 116].
Both art silent on His-tag in their disclosures.
However, incorporating His-tag in the construct of desired protein expression and its technology is well known and well established in the art, since it allows an easy purification of proteins. For example, Gaberc-Porekar teaches advantages of His-tag in protein purification and states that attachment of oligo-histidine tag (His-tag) to the protein N- or C-terminus is a good example of early and successful protein engineering to design a unique and generalized purification scheme for virtually any protein [see abstract]. Therefore, a skilled person in the art would be motivated to incorporate His-tag in the construct of gamma chain of fibrinogen in the teachings of Bolyard or Osther and arrive at applicants product with a reasonable expectation of success.
With regard to SEQ ID NO:3 in the claim, the cited SEQ ID NO:3 is nothing both conjugate of gamma chain of fibrinogen and His-tag. Bolyard or Osther teach gamma chain of fibrinogen, but silent on His-tag. This can be cured by teachings of Kambadur, which teaches His-tag sequence [see SEQ ID NO:13], which meets applicants “at least 80% sequence identity”.
So, applicants individual components are known in the art and art also teaches advantages of His-tag. Therefore, a skilled person in the art would be motivated to incorporate His-tag in the gamma chain fibrinogen, because of its advantages in protein purification. So, the combination reads applicants claim.
For claim 2:
Since both viz., Bolyard or Osther, teach gamma chain of fibrinogen, and so, the claimed binding sites must be present in their disclosed gamma chain of fibrinogen. Moreover, the SEQ ID NO:11 in the disclosure of Osther is identical to applicants gamma chain of fibrinogen.
For claim 3:
The SEQ ID NO:11 in the disclosure of Osther is identical to applicants SEQ ID NO:1 or at least has 80% sequence identity.
For claim 4:
Both viz., Bolyard or Osther, silent on claimed SEQ ID NO:2, which is a His-tag sequence. This can be cured by Kambadur, which teaches His-tag sequence [see SEQ ID NO:13], which meets applicants “at least 80% sequence identity”.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual sequences and advantages of His-tag, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed product with a reasonable expectation of success.
The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983).
Conclusion
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 SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658