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 .
This is the first action on the merits.
Election/Restrictions
Applicant's election without traverse of Group (III) in the reply filed on May 4, 2026 is acknowledged. Group (III), drawn to a process of synthesizing bilirubin, embraced by claims 5-13 was elected by Applicant. Applicant has not pointed to any errors in the Examiner’s analysis of the classification of the different inventions. The requirement is still deemed proper and is therefore made FINAL.
Claims 5-13 are pending and under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Regarding claim 5, the preamble is drawn to a method of synthesizing bilirubin. However, the definitions of X, Y, R1, R1’, R2’ and R2 substituents are broader than that for bilirubin, which is a single compound. Moreover, the process does not provide the steps to obtain bilirubin when formula 2 is outside of the scope of bilirubin. Furthermore, claims 6 and 7 are draw to a PEG derivative of compounds 2 and 3, which is also outside of the scope of bilirubin. Therefore, claims 5-13 are vague.
The following is a quotation of the fourth paragraph of 35 U.S.C. 112:
Subject to the [fifth paragraph of 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6 and 7 are rejected under 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 6 and 7 are draw to a PEG derivative of compounds 2 and 3, which are also outside of the scope of bilirubin. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim Rejections - 35 USC § 103
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 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(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 5-13 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Sabido et al. (Monatsh. Chem., 2014, 145, 775-789, cited on the IDS) in view of Martin et al. (Organic Process Research & Development, 2010, 140, 799-804).
The present claim 5 embraces a method of synthesizing bilirubin comprising reacting a compound of formula 3 with a compound of formula 4 as shown below, wherein X and X’ are vinyl or ethyl substituted with OH or halogen and Y and Y’ are methyl:
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A similar coupling reaction is found in claims 10 and 11.
Sabido et al. teach the following reaction between a compound of formula 6 and 7 to afford a compound of formula 1, wherein X and X’ are ethyl and Y and Y’ are methyl:
:
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, see page 778, Scheme 1.
The only differences between the claimed reaction and the cited reaction are 1) the substitution on X and X’, which is an unsubstituted ethyl versus Applicant’s vinyl or ethyl substituted with OH of halogen; and 2) compound 7 is a di-pyrrole versus Applicant’s tri-pyrrole of formula 3.
1) The use of analogous reactants in a known process is prima facie obvious. In re Durden, 226 USPQ 359 (1985). Once the general reaction has been shown to be old, the burden is on Applicants to present reasons or authority for believing that a group on the starting material would take part in or affect the basic reaction and thus alter the nature of the product or the operability of the process. In looking at the instant claimed process as a whole, as stated in In re Ochiai, 37 USPQ 2d 1127 (1995), the claimed process would have been suggested to one skilled in the art.
2) The tri-pyrrole is inherently produced in the Sabido process before adding a second compound of formula 6 to afford the final product.
Claims 9, 12 and 13 are further drawn to substituting a carboxyl group bonded to the pyrrole group of formulas 6, 9 and 7 to produce a compound of formulas 3, 7 and 8, respectfully.
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Sabido et al. teach the conversion shown below by treating compound 9 with trifluoroacetic acid to deprotect the t-butyl ester groups, decarboxylate the carboxylic acids, followed by reaction with trimethylorthoformate to give aldehyde 2, see below and page 778, Scheme 2, and right-hand column:
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Claim 8 is further drawn to reacting a compound of Formula 1 with Formula 5 to prepare a compound of Formula 3:
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Martin et al. teach a similar process between two compound 12 where Br2 is used for the reaction to afford compound 13: This makes the bridged methylene between the pyrrole rings. While the compounds are different, the process provides the reaction that forms the same methylene between the two pyrroles.
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Claims 6 and 7 appear to be outside of the scope of the present claim 5, since there is no reason to add PEG to compounds of Formula 2 or 3, then remove PEG, in the synthesis of bilirubin.
Therefore, it would be obvious to make bilirubin as outlined in the rejection since Sabido et al. and Martin et al. provide the teachings to do so.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 5-7 and 9-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1-3 and 10-15 of copending Application No. 18291336. Although the claims at issue are not identical, they are not patentably distinct from each other.
The present claim 5 is directed towards a method of synthesizing bilirubin by coupling a compound of Formula 4 with a mono-aldehyde compound of Formula 3 to form a compound of Formula 4, shown below, where R1 and R1’ are each independently hydrogen, an alkyl group having 1 to 12 carbon atoms, an aryl group having 6 to 20 carbon atoms, a heteroaryl group having 2 to 20 carbon atoms, an arylalkyl group having 7 to 20 carbon atoms, or a heteroarylalkyl group having 3 to 20 carbon atoms; R2 and R2’ are each hydrogen or a nitrogen protective group; and any one of X, X’, Y, and Y’ are a vinyl group, an acetyl group, a halogen atom, or an ethyl group substituted with a hydroxyl group, selenide, or sulifde, while the other is a methyl group.
[Formula 3] + [Formula 4] [Wingdings font/0xE0] [Formula 2]
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This is embraced by claim 1 of the ‘336 application, which is directed towards a method of synthesizing bilirubin by coupling a compound of Formula 2 with a bis-aldehyde compound of Formula 1 to form a compound of Formula 3, shown below, where R1 and R2 are each independently hydrogen, an alkyl group having 1 to 12 carbon atoms, an aryl group having 6 to 20 carbon atoms, a heteroaryl group having 2 to 20 carbon atoms, an arylalkyl group having 7 to 20 carbon atoms, or a heteroarylalkyl group having 3 to 20 carbon atoms; R4 is each hydrogen or a nitrogen protective group; R5 is hydrogen; and any one of R3 is hydrogen, a vinyl group, an acetyl group, or an ethyl group substituted with a hydroxyl group, selenide, or sulifde.
[Formula 1] + [Formula 2] [Wingdings font/0xE0] [Formula 3]
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The reference and instant claims share at least one set of overlapping variables. The only difference is that the present claim reacts the mono-aldehyde with the pyrrolidinone, while the claim in the ‘336 application reacts the bis-aldehyde with the pyrrolidinone. However, in the synthesis of the claims of the ‘336 application, Formula 3, the reaction mixture will inherently have bis-aldehyde starting material (instant Formula 1), mono-aldehyde starting material (reference Formula 3), and final product (reference Formula 2, instant Formula 3). Therefore, claim 1 of the ‘336 application reads on the present claim 5. Furthermore, claims 2 and 3 of the ‘336 application, which depend on claim 1, are directed to the same limitations as the present claims 6 and 7, which depended on claim 5. Therefore, the present claims 6 and 7 read on claims 2 and 3 of the ‘336 application.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 5-7 and 9-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1-3 and 10-15 of copending Application No. 18291337. Although the claims at issue are not identical, they are not patentably distinct from each other for the same reasons provided in the NSDP rejection above. The ‘337 application is a similar process as that found in the ‘336 application. Therefore, the same rationale provided above is equally applicable here.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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