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 07/31/2026 are acknowledged.
However, applicants’ arguments for the previous 103 rejection are found not persuasive. Accordingly, the previous rejection is maintained and modified to address claim amendments.
Though some of the claims in the elected group do not read elected species, for example, claims 10-12 and 22 etc., but examined to avoid delay in the prosecution. If applicants think the examined claims 10-12 and 22 are on new grounds, then these ‘examined claims’ in the rejection can be ignored.
In this office action, since claim amendments changed the scope of independent claim, and so, previous rejection is modified. Claims are analyzed/modified and addressed claim by claim to clarify applicants remarks.
Response to Arguments
Applicants argue that (1) the specification contains data for the species identified in the Office Action, together with a side-by-side comparison against the closest exemplified variant.
In fact, examiner was referring to obviate or overcome pending 103 rejection by showing comparative data. Specifically, comparing peptide of prior art with claimed peptides. No such comparison is shown in the specification. Applicants also failed to explain ‘why the combination of prior art’ is not obvious.
Applicants argue that (2) the specification suggests that the outcome of the proposed modifications varied with sequence context and with fatty acid chain length.
Objective evidence of nonobviousness must be commensurate in scope with the scope of the claims. In re Tiffin, 171 USPQ 294.
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).
Claims require peptide of formula (I) bound to fatty acid.
Examples 1 and 2 do not require fatty acid.
Example 4 shows data with various fatty acids. However, rejection already explained the fact that cited art teaches various lengths of fatty acids. It is not clear what applicants intend to prove.
Example 12 shows various peptides and their comparative data, not compared with peptide of prior art. Interestingly, it seems only one peptide shows higher activity. This evidence suggests that applicants may not have possession of broadly claimed subject matter.
Applicants argue that (3) the rationale articulated for the combination is directed to increasing direct antibacterial potency.
The purpose of Chen is to show advantages of additional Lys in an analogous art, regardless of its mechanism. Moreover, Lys is known as cell penetrating amino acid.
Applicants argue that (4) certain claims recite residues that the proposed combination does not appear to reach.
These are addressed in the modified 103 rejection. See the rejection below.
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, 6-13 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Yu (WO 2017/048092 A1 or its equivalent US 2018/0339016 A1) in view of Chen (AJVR, vol.64, No.9, Sep 2003, 1088-1092), Jerala (Expert Opin. Investig. Drugs, 2007, 16(8): 1159-1169) and Albada (ACS Med.Chem.Lett., 2012, 3, 980-984).
For claim 1:
Yu teaches a peptide represented by sequence KLLKL AKKPL KLLK [see SEQ ID NO:55].
Above sequence is identical to applicants X2 to X15 in the claimed formula 1.
Differences between Yu and claims of present application are as follows:
(i) Yu is silent on applicants claimed X1 group, which is K in the elected species.
(ii) Yu is also silent on bound C6 to C16 fatty acid to the peptide.
With regard to (i) of above, incorporation of basic amino acids in antimicrobial peptides are known in the art since these amino acids, viz., K or R, are known to increase the anti-bacterial activity. For example, Chen teaches incorporation of lysine in the short hydrophobic and basic rich peptides increases antibacterial activity [see abstract]. Therefore, a skilled person in the art would be motivated to incorporate basic amino acids to increase the antibacterial activity of short peptides.
With regard to (ii) of above, lipidation of antimicrobial peptides are also known and is a common practice in the art, since it increases the activity of peptides [see review article by Jeral, Expert Opin. Investig. Drugs, 2007, 16(8):1159-1169]. In addition, Albada teaches tuning the activity of short Arg-Trp antimicrobial peptide by lipidation of a C- or N-terminal lysine side-chain with C6-C14 lipids [see abstract; 3rd paragraph in right column in page 981; Table 1]. Therefore, one would be motivated to couple the peptide with fatty acid groups.
Based on above teachings, a skilled person in the art would be motivated to choose lysine for applicants X1 group, because it can meet two functionalities, viz., it can increase antibacterial activity and also can accommodate fatty acid.
For claim 6:
X1 in applicants claimed formula (I) is interpreted as modified amino acid. As explained above, Albada teaches tuning the activity of short Arg-Trp antimicrobial peptide by lipidation of a C- or N-terminal lysine sidechain with C6-C14 lipids [see abstract; 3rd paragraph in right column in page 981; Table 1]. Therefore, one would be motivated to couple the peptide with fatty acid groups at N- or C-terminus.
For claim 7:
See For claim 1 above.
In addition, Yu also teaches Leu for applicants X7. So, both Ala and Leu are equivalents. 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 prior art, the substitution of one equivalent for another is not patentable. See In re Ruff 118 USPQ 343 (CCPA 1958).
Alternatively, the following reasoning and case law are applicable for replacing Ala with Leu at X7:
The issue of patentability over the replacement of alkyl groups for hydrogen or vice versa has arisen many times. For instance, the replacement of a methylene group with a dialkyl-substituted methylene group was determined to be prima facie obvious on the ground that "one skilled in the art would have been, prima facie, motivated to make the claimed compounds in the expectation that they, too, would possess antimicrobial activity." (In re Wood 199 USPQ 137) See also In re Doebel 174 USPQ 158 (where replacement of methyl for hydrogen on an amino nitrogen was considered prima facie obvious - at page 159); In re Druey 138 USPQ 39 (where replacement of methyl for hydrogen on a known compound was considered prima face obvious based on the homologous and close structural relationship to the known compound - at page 41); In re Lohr 137 USPQ 548 (where the replacement of a methyl group for a hydrogen on two positions of a tetrahydropyran ring on a known compound was not considered a patentable modification given the close structural relationship to the known compounds - at page 550); Ex parte Bluestone 135 USPQ 199 (where fungicidal compounds differing by hydrogen versus methyl on the nitrogen of a thiazolidine-2-thione ring were considered homologs and were not found to be patentable over each other without a showing of unexpected results - at page 200); Ex parte Weston 121 USPQ 429 (where the replacement of methyl for hydrogen on the nitrogen of a piperazine ring was not found to be a patentable modification).
The motivation to make a substitution of an alkyl group for hydrogen stems from the fact that a person having ordinary skill in the art would expect that the compounds could be prepared by the same method as taught by the prior art and have the same utility as the compounds taught by the prior art.
MPEP 2144.09 (VII) states "A prima facie case of obviousness based on structural similarity is rebuttable by proof that the claimed compounds possess unexpectedly advantageous or superior properties. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)."
For claim 8:
See For claim 1 above.
For claim 9:
See For claim 1 and For claim 6 above.
For claim 10-12:
See For claim 1 and For claim 6 above.
In addition, Yu is silent on Dab.
Dab and Lys are interpreted as adjacent homologs, since they differ in the length of -CH2- groups.
Please note that adjacent homologs are considered to be obvious absent unexpected results. In re Henze, 85 USPQ 261, 263, CCPA 1950.
When chemical compounds have “very close” structural similarities and similar utilities, a prima facie case of obviousness may be made. In re Grabiak (CAFC 1985) 769 F2d 729, 226 USPQ 870.
"Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties." In re Deuel 34 USPQ2d 1210 at 1214. Furthermore MPEP 2144.09 (II) states: "Compounds which are … of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)."
For claim 13 and 21:
See For claim 1 and For claim 6 above.
For claim 22:
See For claim 1 above.
Yu teaches amphipathic peptides, wherein peptide comprises the cationic charged amino acid is at least 35% based on the total number of amino acids or the hydrophobic amino acid is at least 35% based on the total number of amino acids. [see claims].
The above suggests, hydrophilic and hydrophobic amino acids are exchangeable.
Therefore, based on the guidance provided by Yu, a skilled person in art would be motivated to modify the number of amino acids, either positively chard or hydrophobic amino acids, in the peptide and arrive at applicants peptide with a reasonable expectation of success.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants elected sequence, chemical modifications of amino acids etc., 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 commonly 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 advantage of the teaching of the above cited reference and to make the instantly claimed peptide with a reasonable expectation of success.
A combination of prior art references is only proper if a person of ordinary skill in the art (POSA) at the time of the invention, faced with the same problem, would have been motivated to combine their teachings with a reasonable expectation of success. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Here, the technical fields and problems addressed by the references are not distinct from that of the present claimed invention.
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
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