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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/6/2026 has been entered.
Status of Claims
Currently, claims 69-78, and 102-104 are pending in the instant application. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections constitute the complete set being applied to the instant application. Response to Applicant's arguments follow. This action is NON-FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112
Claims 69-78 and 102-104 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 69 recites “a cDNA having a nucleotide sequence consisting of the nucleotide sequence set forth in SEQ ID NO: 6”. However, the metes and bounds of the claim are confusing because “having” can be open ended, like the term “comprising”. Additionally, “set forth in” encompasses sequences less than the full length of SEQ ID NO: 6. Therefore, the metes and bounds of the nucleic acid molecule being claimed in claim 69 is unclear. If applicant intends the cDNA molecule claimed in claim 69 to be limited to SEQ ID NO: 6, the claim should be amended to recite “a cDNA molecule consisting of the sequence of SEQ ID NO: 6”.
Claim 104 ends in a comma (,) instead of a period (.).
Claim 104 depends from claim 69, and recites “the cDNA according to claim 69, wherein the cDNA is codon optimized”. This is confusing because it is not clear if the recitation implies a) that SEQ ID NO: 6 is already codon optimized, or b) if it intends to claim a different sequence than SEQ ID NO: 6, one that has been codon optimized. From applicant’s arguments regarding the rejections under 35 USC 103, it appears that applicant may be intending to limit claim 69 to “a cDNA molecule consisting of the sequence of SEQ ID NO: 6”. If this is the case, it follows that each interpretation of claim 104 (a and b) explained here is unpatentable because in either situation, claim 104 does not further limit claim 69. In situation a, there is no structural difference in the sequence of claim 104 and the claims are identical in scope. In situation b, claim 104 would be broader than claim 69 because it would allow for a different nucleic acid sequence.
Claim 104 is rejected under 35 U.S.C. 112(d) 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.
Claim 104 depends from claim 69, and recites “the cDNA according to claim 69, wherein the cDNA is codon optimized”. This is confusing because it is not clear if the recitation implies a) that SEQ ID NO: 6 is already codon optimized, or b) if it intends to claim a different sequence than SEQ ID NO: 6, one that has been codon optimized. From applicant’s arguments regarding the rejections under 35 USC 103, it appears that applicant may be intending to limit claim 69 to “a cDNA molecule consisting of the sequence of SEQ ID NO: 6”. If this is the case, it follows that each interpretation of claim 104 (a and b) explained here is unpatentable because in either situation, claim 104 does not further limit claim 69. In situation a, there is no structural difference in the sequence of claim 104 and the claims are identical in scope. In situation b, claim 104 would be broader than claim 69 because it would allow for a different nucleic acid sequence. 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.
Claim Rejections - 35 USC § 103
Claims 69-78 and 104 are rejected under 35 U.S.C. 103 as being unpatentable over ss1711856220 (rs752858122; NCBI, NLM, March 2015; cited in the IDS filed 6/30/2020) in view of Sims (US Patent 7,037,675), and Guven-Maiorov (Guven Maiorov et al; Biophysical Journal, Vol 109; 2015; pages 1214-1226).
Claim interpretation: It is noted that claim 69 recites “a cDNA having a nucleotide sequence consisting of the nucleotide sequence set forth in SEQ ID NO: 6”. However, the term “having” is open ended and allows for nucleotides in addition to those consisting of SEQ ID NO: 6. Additionally, the phrase “set forth in” broadly encompasses sequences within SEQ ID NO: 6. Accordingly, the broadest reasonable interpretation of the claims encompasses a genus of molecules comprising the sequence of SEQ ID NO: 6 as well as molecules comprising sequences in SEQ ID 6. SEQ ID NO: 6 is directed to a cDNA encoding a SIGIRR variant with a deletion mutation that results in a Ser amino acid at position 186 of the encoding protein, and which also causes a frameshift mutation which results in a protein truncated at amino acid 215.
ss1711856220 teaches a variant of a SIGIRR nucleic acid sequence which is directed to a deletion of an A at nucleotide position 555 of the wildtype cDNA encoding SIGIRR. This deletion results in a Ser amino acid at position 186 of the encoding protein, and which also causes a frameshift mutation which results in a protein truncated at amino acid 215. ss1711856220 does not teach a cDNA sequence having (comprising) a nucleotide sequence consisting of SEQ ID NO: 6. however Sims teaches the cDNA sequence of wildtype SIGIRR. An alignment of the relevant portion of the sequence taught by Sims (“Db”) and that of SEQ ID NO: 6 (“Qy”) is provided below.
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The sequence taught by Sims is directed to a cDNA sequence that comprises instant SEQ ID NO: 6 except for the presence of an A at position 555 which is deleted in SEQ ID NO: 6. Sims teaches that the allelic variants of SEQ ID NO: 1 are encompassed as are methods of identifying nucleic acid encoding variant SIGIRR proteins (cols 3-5). With regard to claims 70-78, Sims teaches vector systems comprising cDNA operably linked to a promoter active in a host cell, plasmid and viral vectors, exogenous and inducible promoters, and host cells including E. col, yeast, and mammalian cells for expression of proteins encoded by the cDNA (see cols 19-22). Further, Guven-Maiorov provides a review of the SIGIRR receptor and its role in signaling pathways. Guven-Maiorov teaches that mice lacking SIGIRR are more prone to developing intestinal tumors (page 1218, col 2). Guven-Maiorov teaches that clinically observed SIGIRR mutations have been found in humans, including nonsense and frameshift mutations (see pages 1218, col 2- 1219-col 2; table 2; table S3) that result in a truncated protein. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have constructed a cDNA sequence having (comprising) the sequence of SEQ ID NO: 6 in order to express the truncated protein encoded by the mutation taught by ss1711856220 in view of the known wildtype SIGIRR cDNA taught by Sims. The ordinary artisan would have had a reasonable expectation of success in arriving at a cDNA molecule comprising SEQ ID NO: 6 given the sequence and methods of expressing proteins encoded by cDNA as taught by Sims. The ordinary artisan would have been motivated to construct such a cDNA molecule for the purpose of expressing and analyzing the encoded truncated protein because Guven-Maiorov teaches that clinically relevant oncogenic mutations resulting in truncated SIGIRR variants have been detected in humans. With regard to claim 104, the recitation that the cDNA comprising SEQ ID NO: 6 is codon optimized is considered a property of the cDNA of SEQ ID NO: 6 because codon optimization is dependent on the host system used to express the protein encoded by the cDNA. Since the claims do not recite which host system the codons are optimized for, the recitation does not distinguish the claim from the teachings of the prior art.
Response to Arguments
The response traverses the rejection and asserts that there would have been no motivation to combine the alleged teachings of the cited references. This argument has been thoroughly reviewed but was not found persuasive for the reasons made of record above and in previous office actions.
The response cites to a printout of bioinformatics data “indicated… the nucleic acid molecule of Sims (upper track) has a lengthy 3’ rection that the claimed cDNA does not (lower track). This argument has been thoroughly reviewed but was not found persuasive because no bioinformatics data has been provided.
The response also asserts that Guven-Maiorov fails to remedy the defects of the cited prior art because the reference reports in silico modeling of the interactions of a SIGIRR protein with other proteins which would have rendered redundant the synthesis of the claimed cDNA and translation of a SIGIRR protein therefrom. This argument has been thoroughly reviewed but was not found persuasive because they are applicants arguments and cannot take the place of evidence on the record. Additionally, this argument appears to suggest that since in silico analysis is available, one would not be motivated to synthesize cDNA molecules and translate proteins for analysis, however, no such evidence has been presented to contradict the teachings of Sims, for example. Given that Guven-Maiorov teaches that clinically observed SIGIRR mutations have been found in humans, including nonsense and frameshift mutations (see p.1218, col 2- p.1219-col 2; table 2, table S3) that result in a truncated protein, and that the instantly claimed cDNA results in a truncated protein, the ordinary artisan would have been motivated to characterize and analyze the truncated protein caused by the mutation taught by ss1711856220. To do so, the ordinary artisan would be motivated to construct a cDNA molecules, as taught by Sims. For these reasons, and the reasons already made of record, the rejection is maintained.
Claims 102 and 103 are rejected under 35 U.S.C. 103 as being unpatentable over ss1711856220 (rs752858122; NCBI, NLM, March 2015; cited in the IDS filed 6/30/2020) in view of Sims (US Patent 7,037,675), and Guven-Maiorov (Guven Maiorov et al; Biophysical Journal, Vol 109; 2015; pages 1214-1226) as applied to claims 69-78 above, and further in view of Liang (Liang, P; and Pardee, A,; Nature Reviews – Cancer, vol 3, pages 869-876; 2003).
The teachings of ss1711856220, Sims, and Guven-Maiorov are set forth above. ss1711856220, Sims, and Guven-Maiorov do not teach a cDNA labeled with a fluorescent label. Guven-Maiorov teaches that oncogenic SIGIRR mutations, including ones that result in truncated proteins, are expressed in cancer. Liang teaches strategies for detecting expression of genes in tumor samples, including the construction of fluorescently labeled cDNA. Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date arrive at a fluorescently labeled cDNA suggested by ss1711856220, Sims, and Guven-Maiorov, as taught by Liang, for the purpose of conducting analysis to determine what tissues it is expressed in. Guven-Maiorov teaches that oncogenic SIGIRR mutations, including ones that result in truncated proteins, are expressed in cancer, the ordinary artisan would have been motivated to perform analysis on additional SIGIRR nucleic acid variants, including those that encode truncated proteins, to determine if they are expressed in tumors.
Response to Arguments
The response traverses the rejection for the same reasons as the traversal in section A of the response. This is not found persuasive for the reasons made of record above.
Conclusion
No claims are allowed herein.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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