DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the application
Receipt of applicant’s petition for extension of time filed 08/22/2025 is acknowledged.
However, in absence of either amended claims or arguments in the filed response, the previous rejection is maintained.
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.
I. Claims 16-21 are rejected under 35 U.S.C. 103 as being unpatentable over Ward (US 5,166,136).
For claims 16 and 19:
Ward teaches the following compound:
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, wherein R is a protecting group, m and n are 1 or 2, and R4 is H [see column 4, lines 49-61].
Ward teaches that R represents a nitrogen protecting group this may be for example a nitrogen protecting group useful in conventional peptide synthesis such as an acyl group, for example an acetyl group or an optionally substituted acetyl group (e.g. trifluoroacetyl) or the group R3-OC(O)-, wherein R3 represents for example Cl3CCH2-, (CH3)3C-, C6H5CH2CH2-,
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and
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[see column 2, lines 8-37].
In the above compound, if m and n are 1, R4 is H, and protecting group is acetyl or R3-OC(O)-, wherein R3 is
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, which is nothing but Fmoc, reads applicants claims.
The difference is that Ward teaches racemic mixture of applicants claimed compound, whereas claims require its enantiomers.
However, enantiomers are obvious over their racemic mixture. See established case laws, viz., In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril).
For claims 17 and 20:
Ward teaches that in their compound of formula (VII), the protecting group is R3-OC(O)-, wherein R3 is
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, which is nothing but Fmoc [see column 2, lines 8-37].
For claims 18 and 21:
Ward teaches in their compound of formula (VII), the protecting group is acetyl group [see column 2, lines 8-22].
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.
II. Claims 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Einsiedel (J.Org.Chem., 2007, 72, 9102-9113) in view of Ward (US 5,166,136).
For claims 19-20:
Einsiedel teaches the following compound:
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, wherein R1 is Fmoc [see compound 12 in Scheme 3].
The difference is that in the teachings of Einsiedel both carboxylic and olefin group are attached to different positions on a proline ring (positions 2 and 3), whereas claims require both groups must be on position 2 on the proline ring.
However, these are considered as positional isomers. The MPEP 2144.09 states that “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus)….are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties, see In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
In addition to above, it is also well established that position isomers are prima facie structurally obvious even in the absence of a teaching to modify. The isomer is expected to be preparable by the same method and to have generally the same properties. This expectation is then deemed the motivation for preparing the position isomers. This circumstance has arisen many times. See: Ex parte Englehardt, 208 USPQ 343, 349; In re Mehta, 146 USPQ 284, 287; In re Surrey, 138 USPQ 67; Ex Parte Ullyot, 103 USPQ 185; In re Norris, 84 USPQ 459; Ex Parte Naito, 168 USPQ 437, 439; Ex parte Allais, 152 USPQ 66; In re Wilder, 166 USPQ 545, 548; Ex parte Henkel, 130 USPQ 474; Ex parte Biel, 124 USPQ 109; In re Petrzilka, 165 USPQ 327; In re Crownse, 150 USPQ 554; In re Fouche, 169 USPQ 431; Ex parte Ruddy, 121 USPQ 427; In re Wiechert, 152 USPQ 247, In re Shetty, 195 USPQ 753; In re Jones, 74 USPQ 152, 154; and In re Mayne, 41 USPQ2d 1451 (in which the Court took notice of the extreme similarity between the amino acids Leucine and isoleucine: “In fact, Leu is an isomer of Ile -- an identical chemical formula with differences only in the chemical bonding of the atoms. The side chains…of Leu and Ile have the same number of hydrogen and carbon atoms…The structure of Leu and Ile alone suggest their functional equivalency” (at 1454-1455)).
For example, “Position isomerism has been used as a tool to obtain new and useful drugs” (Englehardt) and “Position isomerism is a fact of close structural similarity” (Mehta, emphasis in the original). Note also In re Jones, 21 USPQ2d 1942, which states at 1943 “Particular types or categories of structural similarity without more, have, in past cases, given rise to prima facie obviousness”; one of those listed is “adjacent homologues and structural isomers”. Position isomers are the basic form of close “structural isomers.” Similar is In re Schechter and LaForge, 98 USPQ 144, 150, which states “a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds.” Note also In re Deuel 34 USPQ2d 1210, 1214 which states, “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds … a known compound may suggest its analogs or isomers, either geometric isomers (cis v. trans) or position isomers (e.g., ortho v. para).” See also MPEP 2144.09, second paragraph.
Accordingly claims are obvious over the teachings of Einsiedel.
For claim 21:
Einsiedel is silent on applicants acetyl group.
However, both acetyl and Fmoc are equivalents for applicants compound(s) as evidenced from the teachings of Ward, wherein the protecting group can be acetyl or Fmoc [see column 2, lines 8-35].
In determining equivalence, "[a]n analysis of the role played by each element in the context of the specific patent claim will thus inform the inquiry as to whether a substitute element matches the function, way, and result of the claimed element, or whether the substitute plays a role substantially different from the claimed element." 520 U.S. at 40, 41 USPQ2d at 1875.
MPEP 2144.06 states that “In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In reRuff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958). In this case, both Fmoc and acetyl groups are recognized groups in the art and have same function, i.e., protecting groups for nitrogen on proline ring.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual protecting groups and their purpose in protecting the same group in proline ring, 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 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).
The motivation to combine 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 compound with a reasonable expectation of success.
III. Claims 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Pfeifer (Helvetica Chimica Acta, 1997, 80, 1513-1527) in view of Thomas (J.C.S. Chem.Comm., 1972, 7880799) and Bodanszky (J.Org.Chem., 1980, 45, 76-80).
Pfeifer teaches the following compound:
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[see Scheme 2 in page 1515].
The difference is that Pfeifer is silent on applicants acetyl or Fmoc protecting groups on N- in the proline ring.
However, both acetyl and Fmoc are well known and commercially successful protecting groups for alpha amino groups in amino acids. Both acetyl and Fmoc protected prolines are known in the art. For example, Thomas teaches Ac-Pro-OH [see page 788], and Bodanszky teaches Fmoc-Pro-OH [see page 76 and its STN registry number 71989-31-6].
The above N-protected proline with acetyl and Fmoc are also commercially available [can be found in commercial catalogs].
In light of above, a skilled person in the art would be motivated to choose commercially known and successful protecting groups, and arrive at applicants compound 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).
The motivation to combine the art 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 compound with a reasonable expectation of success.
IV. Claims 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Khalil (Tetrahedron Letters, 1996, vol.37, No.20, 3441-3444) in view of Thomas (J.C.S. Chem.Comm., 1972, 7880799) and Bodanszky (J.Org.Chem., 1980, 45, 76-80).
Khalil teaches the following compound:
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, wherein R is -CH2CH=CH2 [see Scheme 1 in page 3442].
The difference is that Khalil is silent on applicants acetyl or Fmoc protecting groups on N- in the proline ring.
However, both acetyl and Fmoc are well known and commercially successful protecting groups for alpha amino groups in amino acids. Both acetyl and Fmoc protected prolines are known in the art. For example, Thomas teaches Ac-Pro-OH [see page 788], and Bodanszky teaches Fmoc-Pro-OH [see page 76 and its STN registry number 71989-31-6].
The above N-protected proline with acetyl and Fmoc are also commercially available [can be found in commercial catalogs].
In light of above, a skilled person in the art would be motivated to choose commercially known and successful protecting groups, and arrive at applicants compound 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).
The motivation to combine the art 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 compound with a reasonable expectation of success.
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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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.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658