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 12/05/2025 are acknowledged.
In light of claim amendment, previous Claim Objections is withdrawn.
However, applicants’ arguments for the previous 103 rejection are found not persuasive. Accordingly, the previous rejection is maintained. Please see the examiners response to applicants arguments below.
Response to Arguments
Applicants’ main argument is that none of Dahlen, Betts, and Miyata presents or suggests an IL-1RN protein including a mutated site at any of sites 5, 14, and 74 of SEQ ID NO: 1. And none of Dahlen, Betts presents or suggests any of the specific mutations R5T, R14T, and D74N, of which at least one is required in claim 1.
Applicants show how each cited reference differ from the instant invention, but the obviousness test under 35 U.S.C. 103 is whether the invention would have been obvious in view of the prior art taken as a whole. In re Metcalf et al. 157 U.S.P.Q. 423.
Applicant is reminded that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, all the art rejections are under 35 USC 103, which relies on the combination of the references together.
In this case, combination of cited art reads applicants claimed product. Moreover claims require BRI, at least one of the mutation.
As explained in the rejection, it is common in the art replacing Asp (D) with Asn (N) and these are interchangeable, as evidenced from cited teachings from Betts and Miyata. If the property is opposite, then it is unexpected property. No such evidence is shown either in the response or in the specification.
Further, case law holds that the mere substitution of an equivalent (something equal in value or meaning, as taught by analogous prior art) is not an act of invention; where equivalency is known to the prior art, the substitution of one equivalent for another is not patentable. See In re Ruff 118 USPQ 343 (CCPA 1958).
Applicants further argue that the application as filed sets forth that the mutant Interleukin-1 Receptor Antagonist protein with the substitution of asparagine for aspartic acid at site 74 (IL- 1RND74N) exhibited surprisingly and unexpectedly improved properties over the wild-type IL- 1RN protein. As an experimental example, Table 1 shows that the binding affinity (activity) of the mutant IL-1RND74N protein was more than 10 times greater than the binding affinity (activity) of the wild-type IL-1RN protein. As another experimental example, Figure 10 and pages 13-14 show that the mutant IL-1RND74N protein completely inhibited an inflammatory response over a three-week period in a mouse model of collagen-induced arthritis (CIA), whereas the wild-type IL-1RN protein did not. These surprisingly and unexpectedly favorable properties further support the nonobviousness of the Interleukin-1 Receptor Antagonist protein mutated at site 74 with asparagine substituted for aspartic acid (D74N) of claim 1.
Shown data in Table 1 is limited to fusion proteins and their binding properties. There is no shown data for the claimed SEQ ID NO:1 with the claimed mutations.
“The evidence presented to rebut a prima facie case of obviousness must be commensurate in scope with the claims to which it pertains.” In re Dill, 604 F.2d 1356, 1361 (CCPA 1979).
It is noted that it is Applicant's burden to demonstrate unexpected results over the prior art. See MPEP 716.02, particularly 716.02 (a) - (g). The unexpected results should be demonstrated with evidence that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance. Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). Moreover, evidence as to any unexpected benefits must be "clear and convincing" In re Lohr, 137 USPQ 548 (CCPA 1963), and be of a scope reasonably commensurate with the scope of the subject matter claimed, In re Linder, 173 USPQ 356 (CCPA 1972).
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 is rejected under 35 U.S.C. 103 as being unpatentable over Dahlen (US 2015/0368318 A1) in view of Betts (Bioinformatics for Geneticists, Chapter 14, 289-316, 2003, Ed by Michael R Barnes and Ian C. Gray) and Miyata (J.Mol.Evol., 1979, 12, 219-236).
Dahlen teaches interleukin-1 receptor antagonist represented by SEQ ID NO:1, which is identical to applicants SEQ ID NO:1.
Difference is that Dahlen is silent on applicants claimed ‘at least one of the mutation in the sequence’, for example, D74N.
However, it is common in the art replacing Asp (D) with Asn (D) and these are interchangeable.
For example, Betts teaches that Asp can be substituted asparagine, which differs only in that it contains an amino group in place of one of the oxygens found in Asp [see page 305].
Further, Miyata teaches that amino acid pair distance for Asp and Asn is 0.65 or 0.80 [see Tables 1 and 2], which means a high degree of similarity and high likelihood of them being interchangeable while preserving protein function and structure.
Therefore, Asp and Asn are equivalents and so, are exchangeable.
Case law holds that the mere substitution of an equivalent (something equal in value or meaning, as taught by analogous prior art) is not an act of invention; where equivalency is known to the prior art, the substitution of one equivalent for another is not patentable. See In re Ruff 118 USPQ 343 (CCPA 1958).
Further, the USPTO has provided rationale for determining obviousness. MPEP § 2143 sets forth some rationales that were established in KSR International Co. v Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). Exemplary rationales that may support a conclusion of obviousness include:
(a) Combining prior art elements according to known methods to yield predictable results;
(b) Simple substitution of one known element for another to obtain predictable results;
(c) Use of known technique to improve similar devices (methods, or products) in the same way;
(d) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(e) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success
(f) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other BIRCH, STEWART, KOLASCH & BIRCH, LLPJWB/thd market forces if the variations are predictable to one of ordinary skill in the art;
(g) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
At least (a), (b) and (e) are applicable or supports obviousness over the art.
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 protein 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.
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://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. 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://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.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.
SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658