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 .
Claim 14 has been canceled. Claims 1-13 remain pending.
Election/Restrictions
Applicant’s election of Group II, claims 4-7, in the reply filed on 9-16-25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 10-13 have been amended to be drawn to the method of claims 5 or 6 and have been combined with Group II.
Claims 1-3, 8, 9 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9-16-25.
Claims 4-7, 10-13 are under consideration; however, further restriction based on using the nucleic acid sequence vs. the protein for grading tumors will be required if the claims become too complicated. The kit for diagnosing or grading tumor in claim 7 may also require further restriction upon delineating patentably distinct means of testing using nucleic acid assays (e.g. PCR) vs. protein assays.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 4 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. Claim 4 does not fall within at least one of the four categories of patent eligible subject matter because the claim is drawn to a “Use” of a nucleic acid sequence/protein. This is not an acceptable claim in US practice. The claim must be drawn to a Method (of using) the nucleic acid sequence/protein.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 4-7, 10-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 4 is drawn to a “Use of the nucleic acid molecule as defined in claim 1(J)(g) or the protein or peptide as defined in claim 1 in a sample obtained from a subject for diagnosing a tumor and/or for grading a tumor and/or for tumor prognosis and/or classifying tumor as a HLA-H low expression tumor or a HLAH high expression tumor and/or for diagnosing an implantation failure”.
Claim 4 is drawn to “A nucleic acid molecule, a vector, a host cell, or a protein or peptide, or combinations thereof for use as an immunosuppressant, as a tumor vaccine or as a pregnancy promoter wherein (I) the nucleic acid molecule is (a) encoding a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1 or 54; or (b) consisting of the nucleotide sequence of SEQ ID NO: 2; or (c) encoding a polypeptide which is at least 95% identical to the amino acid sequence of SEQ ID NO: 1 or 54; or (d) consisting of a nucleotide sequence which is 95% identical to the nucleotide sequence of SEQ ID NO: 2; or (e) consisting of a nucleotide sequence which is degenerate with respect to the nucleic acid molecule of (d); or (f) a fragment of the nucleic acid molecule of any one of (a) to (e), said fragment comprising at least 250 nucleotides, preferably at least 300 nucleotides, more preferably at least 450 nucleotides, and most preferably at least 600 nucleotides; or (g) corresponding to the nucleic acid molecule of any one of (a) to (f), wherein T is replaced by U; (II) the vector comprises the nucleic acid molecule of (I);(III) the host cell is transformed, transduced or transfected with the vector of (II); and (IV) the protein or peptide being encoded by the nucleic acid molecule of (I).”
5. (Original) A method for diagnosing a tumor comprising detecting the presence of the nucleic acid molecule as defined in claim 1(J)(g) and/or the protein or peptide as defined in claim 1 in a sample obtained from a subject, wherein the presence of the nucleic acid molecule as defined in claim 1(I)(g) and/or the protein as defined in claim 1 is indicative for a tumor in the subject.
6. (Original) A method for grading a tumor and/or for tumor prognosis comprising determining the level of the nucleic acid molecule of as defined in claim 1(J)(g) and/or the protein or peptide as defined in claim 1 in a sample obtained from a subject, wherein increased levels of the nucleic acid molecule as defined in claim 1(I)(g) and/or the protein or peptide as defined in claim 1 as compared to a control correlate with the a higher grade of the tumor and/or an adverse tumor prognosis.
7. (Original) Kit for diagnosing a tumor and/or for grading a tumor and/or for tumor prognosis, comprising (a) means for the detection and/or quantification of the nucleic acid molecule as defined in claim 1(J)(g) and/or the protein or peptide as defined in claim 1 in a sample obtained from a subject, and (b) instructions for using the kit.
Claim 4 encompasses using any amino acid sequence of that is 95% identical to SEQ ID NO: 1 or 54, a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 1 or 54, or the nucleic acid sequence of SEQ ID NO: 2 to “diagnose” or “grade” any tumor, “for tumor prognosis”, “as a HLA-H low expression tumor”, as a “HLA-H high expression tumor”, or “for diagnosing an implantation failure”.
Claim 4 also encompasses using any fragment of at least 250 nucleotides of SEQ ID NO: 2 to do the same functions.
Claim 4 also (somehow) encompasses using a vector or host cell comprising the sequences to do the same functions.
Pg 4-5 says SEQ ID NO: 1 is an HLA-H protein. Pg 6, line 1, says HLA-H has immunosuppressive capability.
Pg 7, line 4-18, defines when a sequence is “degenerate” (“degeneracy of the genetic code”). Pg 7, lines 18-38, discusses fragments.
Detection of HLA-H is discussed on pg 16, lines 21-29.
Unexpectedly, HLA-H is not a pseudogene but a functional gene encoding a protein (pg 16, lines 31-32, 35-36). Even more unexpectedly, the protein is not amino acid sequence UniPortKB: P01893 but the amino acid sequence of SEQ ID NO: 1 (pg 16, lines 36-37).
Pg 17, lines 15-18, says: “WO 2018/140525 envisions the use of an HLA-H antibody for the treatment of cancer, WO 2018/140525 does not disclose any HLA-H, let alone the correct HLA-H sequences of SEQ ID NOs 1 and 2 as provided herein. Similarly, WO 2018/183921 refers to a long list of potential novel immunotherapy targets, wherein HLA-H is among this list. Again, no HLA-H sequences are disclosed”.
Thus, the art at the time of filing did not teach how to use the amino acid sequence of SEQ ID NO: 1 or 54 or nucleic acid sequences encoding them to “diagnose” or “grade” any tumor, “for tumor prognosis”, “as a HLA-H low expression tumor”, as a “HLA-H high expression tumor”, or “for diagnosing an implantation failure” as required in claim 4.
Pg 18-30 appear to relate to things that target the HLA-H or nucleic acids encoding them and have nothing to do with using the sequences to “diagnose” or “grade” any tumor, “for tumor prognosis”, “as a HLA-H low expression tumor”, as a “HLA-H high expression tumor”, or “for diagnosing an implantation failure”.
Pg 30, line 35, through pg 34, line 7, and pg 37, line 8, through pg 38, line 10, contemplates using the HLA-H or sequences encoding them to “diagnose” or “grade” any tumor, “for tumor prognosis”, “as a HLA-H low expression tumor”, as a “HLA-H high expression tumor”, or “for diagnosing an implantation failure”.
Pg 38, lines 25-32, says HLA-H is expressed in tumors at various stages and used by the tumors to escape the immune system and points to Example 4.
Pg 40, lines 6-14, discusses the tumor types.
Example 1 (pg 44) discusses bladder carcinoma and “four molecular subtypes” “defined based on mRNA expression patterns” as subtypes I, II, III, IV. The specification does not teach the four molecular subtypes are HLA-H, SEQ ID NO: 1, 2, 54 or fragments thereof as required in claims 4-7. Pg 45, line 5, points to Figure 1 which shows the amount of HLA-H “pseudogene” expression. The specification does not HLA-H “pseudoene” encodes SEQ ID NO: 1 or 54 or fragments thereof or is SEQ ID NO: 2 or a fragment thereof. Pg 45, line 9, points to Figure 2 which compares HLA-H expression to “luminal subtype markers (ESR2, ERBB2, ERBB3, CDH1, KRT20, KRT5) and epithelial-mesenchymal-transition markers SNAI1-3. Pg 45, line 20, points to Figure 3 and says “HLA-H mRNA expression was significantly associated with non papillary histological subtype (p= 0.0029). With regard to other clinical variables such as gender, age, or lymph node status no significant association could be found.”
Example 2 (pg 45, line 24) describes analyzing HLA expression levels using RT-PCR in bladder cancer tissue samples from patients being treated with antibodies. Fig. 5 compares HLA-H expression in various bladder cancer specimens and observed a correlation of HLA-H and CD44 coexpression but not a significant correlation with CK5, CK20, FOXA1, GATA3. Fig. 6 compares HLA-H expression in various bladder cancer specimens and observed a correlation of HLA-H and PDL1 coexpression but not a significant correlation with KRT5, KRT20, PD1.
Fig. 8 (pg 48) shows “advanced or metastatic urothelial cancer patients exhibited significantly worse disease specific survival as determined from start of first, second or third line treatment with immunemodulatory checkpoint inhibitors such as atezolizumab, pembrolizumab or nivolumab if the primary, FGFR2 negative tumor does express HLA-H as determined by RNA specific RT-qPCR”.
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It is unclear how HLA-H or any other combination of markers indicates any specific “diagnosis” or “grading” or “prognosis” of a tumor because they amount of HLA-H expression or the combination of HLA-H along with other markers required for any specific diagnosis, grade, or prognosis is missing from the discussion and the specification as a whole.
Fig. 9 shows an “adverse outcome upon HLA-H expression” “in the metastasized situation” (pg 49, line 15). However, the specific amount of HLA-H expression or the combination of HLA-H along with other markers required for any specific diagnosis, grade, or prognosis is missing from the specification. The specific combination of HLA-H along with other markers required for any specific diagnosis, grade, or prognosis is missing from the specification. It is unclear how HLA-H or any other combination of markers indicates any specific diagnosis, grade, or prognosis of a tumor as claimed.
Fig. 10 is discussed on pg 49, lines 22-27, but with no clarification.
Fig. 11 is discussed on pg 49, line 38, through pg 50, line 2, but with no clarification.
The description of Fig. 12 says HLA-H exon 2/exon 3 isoforms are “associated with inferior disease specific survival in patients with more than 5% PDL1 positive immune cells and with HLA-H exon 2/3 positive patients having a survival probability of only 10% after 1 year, while HLA-H exon 2/3 negative patients and patients having no or lower frequencies of PDL1 positive immune cells had a survival probability of 60% after 1 year”. These results are limited to coexpression of HLA-H and PDL1 which is missing from the claim.
The results in Fig. 8-12 are limited to the presence of a specific HLA-H isoform at exon 2/3 which is missing from the claim. These results are limited to bladder cancer which is missing from the claim. There is nothing in this data for using HLA-H expression alone for diagnosing, grading, or prognosing a tumor as broadly encompassed by the claims. There is nothing in this data that says HLA-H expression level of x indicates diagnosis y or z. There is nothing in this data that says HLA-H expression level of x in combination with expression of A, B, or C indicates diagnosis y or z. The same applies to “grades” of tumors and “prognosis”.
The specification does not correlate using nucleic acid sequences encoding HLA-H from tumor samples to using nucleic acid sequences encoding HLA-H from non-tumor samples as broadly claimed. The specification does not correlate using nucleic acid sequences encoding HLA-H from tumor samples to using HLA-H protein samples as broadly claimed.
The specification lacks written description for using HLA-H expression levels to diagnose, grade, or prognose any breast, ovarian, endometrial, vaginal…leukemia as broadly encompassed by claim 11 for reasons set forth above.
The specification lacks written description for using HLA-H expression levels to diagnose, grade, or prognose any bladder or gynecologic cancer as broadly encompassed by claim 12 for reasons set forth above.
The specification lacks written description for using HLA-H expression levels to diagnose, grade, or prognose any breast or ovarian cancer as broadly encompassed by claim 13 for reasons set forth above.
The specification lacks written description for using any nucleotide sequence that is at least 95% identical to SEQ ID NO: 2, any “degenerate” nucleic acid that is at least 95% identical to SEQ ID NO: 2 or any fragment of at least 250 nucleotides thereof for diagnosing, grading or prognosing a tumor as broadly encompassed by claims 4-7. The specification and examples are limited to using a specific region between exons 2 and 3 of a specific HLA-H isoform which is not in the claim. The specification does not teach any sequences at this specific region that is at least 95% identical to SEQ ID NO: 2. The specification does not teach any fragments of at least 250 nucleotides at this specific region or anywhere else within SEQ ID NO: 2 that are capable of diagnosing, grading, or prognosing any tumor.
The specification lacks written description for any using proteins encoded by such nucleic acids as broadly encompassed by claims 4-7 via item IV) of claim 1 for diagnosing, grading, or prognosing any tumor. The specification does not teach any such proteins or using proteins for diagnosing, grading, or prognosing any tumor. In particular, the specification does not teach any peptides encoded by any nucleic acid that is at least 250, 300, 450, or 600 nucleotides of SEQ ID NO: 2 for diagnosing, grading, or prognosing any tumor as broadly encompassed by claims 4-7 via item IV) of claim 1.
Accordingly, the specification fails to adequately describe how to use HLA-H expression for diagnosing, grading, or prognosing a tumor as broadly encompassed by the claims.
Claims 4-7, 10-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for detecting a nucleic acid sequence encoding HLA-H, does not reasonably provide enablement for using expression level of HLA-H as a means of diagnosing, grading, or prognosing tumors. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
The claims and their scopes are discussed above.
Pg 4-5 says SEQ ID NO: 1 is an HLA-H protein. Pg 6, line 1, says HLA-H has immunosuppressive capability.
Pg 7, line 4-18, defines when a sequence is “degenerate” (“degeneracy of the genetic code”). Pg 7, lines 18-38, discusses fragments.
Detection of HLA-H is discussed on pg 16, lines 21-29.
Unexpectedly, HLA-H is not a pseudogene but a functional gene encoding a protein (pg 16, lines 31-32, 35-36). Even more unexpectedly, the protein is not amino acid sequence UniPortKB: P01893 but the amino acid sequence of SEQ ID NO: 1 (pg 16, lines 36-37).
Pg 17, lines 15-18, says: “WO 2018/140525 envisions the use of an HLA-H antibody for the treatment of cancer, WO 2018/140525 does not disclose any HLA-H, let alone the correct HLA-H sequences of SEQ ID NOs 1 and 2 as provided herein. Similarly, WO 2018/183921 refers to a long list of potential novel immunotherapy targets, wherein HLA-H is among this list. Again, no HLA-H sequences are disclosed”.
Thus, the art at the time of filing did not teach how to use the amino acid sequence of SEQ ID NO: 1 or 54 or nucleic acid sequences encoding them to “diagnose” or “grade” any tumor, “for tumor prognosis”, “as a HLA-H low expression tumor”, as a “HLA-H high expression tumor”, or “for diagnosing an implantation failure” as required in claim 4.
Pg 18-30 appear to relate to things that target the HLA-H or nucleic acids encoding them and have nothing to do with using the sequences to “diagnose” or “grade” any tumor, “for tumor prognosis”, “as a HLA-H low expression tumor”, as a “HLA-H high expression tumor”, or “for diagnosing an implantation failure”.
Pg 30, line 35, through pg 34, line 7, and pg 37, line 8, through pg 38, line 10, contemplates using the HLA-H or sequences encoding them to “diagnose” or “grade” any tumor, “for tumor prognosis”, “as a HLA-H low expression tumor”, as a “HLA-H high expression tumor”, or “for diagnosing an implantation failure”.
Pg 38, lines 25-32, says HLA-H is expressed in tumors at various stages and used by the tumors to escape the immune system and points to Example 4.
Pg 40, lines 6-14, discusses the tumor types.
Example 1 (pg 44) discusses bladder carcinoma and “four molecular subtypes” “defined based on mRNA expression patterns” as subtypes I, II, III, IV. The specification does not teach the four molecular subtypes are HLA-H, SEQ ID NO: 1, 2, 54 or fragments thereof as required in claims 4-7. Pg 45, line 5, points to Figure 1 which shows the amount of HLA-H “pseudogene” expression. The specification does not HLA-H “pseudoene” encodes SEQ ID NO: 1 or 54 or fragments thereof or is SEQ ID NO: 2 or a fragment thereof. Pg 45, line 9, points to Figure 2 which compares HLA-H expression to “luminal subtype markers (ESR2, ERBB2, ERBB3, CDH1, KRT20, KRT5) and epithelial-mesenchymal-transition markers SNAI1-3. Pg 45, line 20, points to Figure 3 and says “HLA-H mRNA expression was significantly associated with non papillary histological subtype (p= 0.0029). With regard to other clinical variables such as gender, age, or lymph node status no significant association could be found.”
Example 2 (pg 45, line 24) describes analyzing HLA expression levels using RT-PCR in bladder cancer tissue samples from patients being treated with antibodies. Fig. 5 compares HLA-H expression in various bladder cancer specimens and observed a correlation of HLA-H and CD44 coexpression but not a significant correlation with CK5, CK20, FOXA1, GATA3. Fig. 6 compares HLA-H expression in various bladder cancer specimens and observed a correlation of HLA-H and PDL1 coexpression but not a significant correlation with KRT5, KRT20, PD1.
Fig. 8 (pg 48) shows “advanced or metastatic urothelial cancer patients exhibited significantly worse disease specific survival as determined from start of first, second or third line treatment with immunemodulatory checkpoint inhibitors such as atezolizumab, pembrolizumab or nivolumab if the primary, FGFR2 negative tumor does express HLA-H as determined by RNA specific RT-qPCR”.
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It is unclear how HLA-H or any other combination of markers indicates any specific “diagnosis” or “grading” or “prognosis” of a tumor because they amount of HLA-H expression or the combination of HLA-H along with other markers required for any specific diagnosis, grade, or prognosis is missing from the discussion and the specification as a whole.
Fig. 9 shows an “adverse outcome upon HLA-H expression” “in the metastasized situation” (pg 49, line 15). However, the specific amount of HLA-H expression or the combination of HLA-H along with other markers required for any specific diagnosis, grade, or prognosis is missing from the specification. The specific combination of HLA-H along with other markers required for any specific diagnosis, grade, or prognosis is missing from the specification. It is unclear how HLA-H or any other combination of markers indicates any specific diagnosis, grade, or prognosis of a tumor as claimed.
Fig. 10 is discussed on pg 49, lines 22-27, but with no clarification.
Fig. 11 is discussed on pg 49, line 38, through pg 50, line 2, but with no clarification.
The description of Fig. 12 says HLA-H exon 2/exon 3 isoforms are “associated with inferior disease specific survival in patients with more than 5% PDL1 positive immune cells and with HLA-H exon 2/3 positive patients having a survival probability of only 10% after 1 year, while HLA-H exon 2/3 negative patients and patients having no or lower frequencies of PDL1 positive immune cells had a survival probability of 60% after 1 year”. These results are limited to coexpression of HLA-H and PDL1 which is missing from the claim.
The results in Fig. 8-12 are limited to the presence of a specific HLA-H isoform at exon 2/3 which is missing from the claim. These results are limited to bladder cancer which is missing from the claim. There is nothing in this data for using HLA-H expression alone for diagnosing, grading, or prognosing a tumor as broadly encompassed by the claims. There is nothing in this data that says HLA-H expression level of x indicates diagnosis y or z. There is nothing in this data that says HLA-H expression level of x in combination with expression of A, B, or C indicates diagnosis y or z. The same applies to “grades” of tumors and “prognosis”.
The specification does not correlate using nucleic acid sequences encoding HLA-H from tumor samples to using nucleic acid sequences encoding HLA-H from non-tumor samples as broadly claimed. The specification does not correlate using nucleic acid sequences encoding HLA-H from tumor samples to using HLA-H protein samples as broadly claimed.
The specification does not enable using HLA-H expression levels to diagnose, grade, or prognose any breast, ovarian, endometrial, vaginal…leukemia as broadly encompassed by claim 11 for reasons set forth above.
The specification does not enable using HLA-H expression levels to diagnose, grade, or prognose any bladder or gynecologic cancer as broadly encompassed by claim 12 for reasons set forth above.
The specification does not enable using HLA-H expression levels to diagnose, grade, or prognose any breast or ovarian cancer as broadly encompassed by claim 13 for reasons set forth above.
The specification does not enable using any nucleotide sequence that is at least 95% identical to SEQ ID NO: 2, any “degenerate” nucleic acid that is at least 95% identical to SEQ ID NO: 2 or any fragment of at least 250 nucleotides thereof for diagnosing, grading or prognosing a tumor as broadly encompassed by claims 4-7. The specification and examples are limited to using a specific region between exons 2 and 3 of a specific HLA-H isoform which is not in the claim. The specification does not teach any sequences at this specific region that is at least 95% identical to SEQ ID NO: 2. The specification does not teach any fragments of at least 250 nucleotides at this specific region or anywhere else within SEQ ID NO: 2 that are capable of diagnosing, grading, or prognosing any tumor.
The specification does not enable using any using proteins encoded by such nucleic acids as broadly encompassed by claims 4-7 via item IV) of claim 1 for diagnosing, grading, or prognosing any tumor. The specification does not teach any such proteins or using proteins for diagnosing, grading, or prognosing any tumor. In particular, the specification does not teach any peptides encoded by any nucleic acid that is at least 250, 300, 450, or 600 nucleotides of SEQ ID NO: 2 as broadly encompassed by claims 4-7 via item IV) of claim 1.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to use HLA-H expression for diagnosing, grading, or prognosing a tumor as broadly encompassed by the claims.
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 4-7, 10-13 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 4-7 are indefinite because they are limited to using nucleic acids or proteins for diagnosing, grading, or prognosing tumors, but they are dependent upon claim 1 which encompasses, nucleic acids, proteins, vectors, host cells or combinations thereof. So referring to “the protein or peptide defined in claim 1” in claim 4, for example, is inaccurate because claim encompasses more. Claim 4 does not refer to the protein or peptide of claim 1 (IV).
The metes and bounds of a “HLA-H low expression tumor” and a “HLAH high expression tumor” in claim 4 cannot be determined. The specification discusses the phrases on pg 33, lines 1-13, without defining the metes and bounds. There is nothing in the specification or art at the time of filing that says whether the level encompasses explicit data, i.e. an RT-PCR result of X indicates “low” HLAH expression, or whether the result is a comparison over time or to another tissue type or to another tumor type. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
The phrase “diagnosing an implantation failure” in claim 4 does not make sense in context of claim 4 because nothing has been implanted. Furthermore, it is unclear when an “implantation” is a failure because the metes and bounds of the concept have not been defined in the specification or the art at the time of filing. Therefore, those of skill would not be able to determine when an HLA-H nucleic acid sequence or HLA-H expression level indicated “implantation failure”.
The metes and bounds of when an HLA-H protein or nucleic acid sequence indicates the presence of a tumor as broadly encompassed by claim 4 and specifically required in claim 5 cannot be determined. There is nothing in the specification or art at the time of filing that says when an HLA-H protein or nucleic acid sequence level indicates the presence of a tumor, i.e. an RT-PCR result of HLAH at level X indicates the presence of a tumor. It is unclear whether the observation of HLAH expression is a comparison over time or to another tissue type or to another tumor type. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
The metes and bounds of when an HLA-H protein or nucleic acid sequence indicates the grade or prognosis of a tumor as broadly encompassed by claim 4 and specifically required in claim 6 cannot be determined. There is nothing in the specification or art at the time of filing that says when an HLA-H protein or nucleic acid sequence level indicates the grade or prognosis of a tumor, i.e. an RT-PCR result of HLAH at level X indicates the tumor is stage II. It is unclear whether the observation of HLAH expression is a comparison over time or to another tissue type or to another tumor type. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 7 is rejected under 35 U.S.C. 102a1 as being anticipated by Betsholtz (20060216722).
Betsholtz taught a nucleic acid sequence that encodes a protein that is at least 97.2% identical to SEQ ID NO: 1:
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Betshotlz taught identifying the sequence using antibodies and PCR which are kits for diagnosing/grading/prognosing tumor because they are means for detecting and quantifying the presence of sequences encoding the HLAH of SEQ ID NO: 1 (para 8-11; para 164).
Claim 7 is rejected under 35 U.S.C. 102a1 as being anticipated by Abbas (20090186034).
Abbas taught a protein that is at least 94.1% identical to SEQ ID NO: 54:
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Abbas taught identifying the sequence using antibodies and PCR (para 13, 29, 489, 491, 496, 498, 504-510) (para 44, 587) which are kits for diagnosing, grading, prognosing tumor because they are means for detecting and quantifying the presence of sequences encoding the fragments of HLAH of SEQ ID NO: 54 that are at least 250 nucleotides as broadly encompassed by claim 7.
The art at the time of filing did not reasonably teach or suggest “A nucleic acid molecule, a vector, a host cell, or a protein or peptide, or combinations thereof for use as an immunosuppressant, as a tumor vaccine or as a pregnancy promoter wherein (I) the nucleic acid molecule is (a) encoding a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1 or 54; or (b) consisting of the nucleotide sequence of SEQ ID NO: 2; or (c) encoding a polypeptide which is at least 95% identical to the amino acid sequence of SEQ ID NO: 1 or 54; or (d) consisting of a nucleotide sequence which is 95% identical to the nucleotide sequence of SEQ ID NO: 2; or (e) consisting of a nucleotide sequence which is degenerate with respect to the nucleic acid molecule of (d); or (f) a fragment of the nucleic acid molecule of any one of (a) to (e), said fragment comprising at least 250 nucleotides, preferably at least 300 nucleotides, more preferably at least 450 nucleotides, and most preferably at least 600 nucleotides; or (g) corresponding to the nucleic acid molecule of any one of (a) to (f), wherein T is replaced by U; (II) the vector comprises the nucleic acid molecule of (I);(III) the host cell is transformed, transduced or transfected with the vector of (II); and (IV) the protein or peptide being encoded by the nucleic acid molecule of (I)” as required in claim 4.
The art at the time of filing did not reasonably teach or suggest “A method for diagnosing a tumor comprising detecting the presence of the nucleic acid molecule as defined in claim 1(J)(g) and/or the protein or peptide as defined in claim 1 in a sample obtained from a subject, wherein the presence of the nucleic acid molecule as defined in claim 1(I)(g) and/or the protein as defined in claim 1 is indicative for a tumor in the subject” as required in claim 5.
The art at the time of filing did not reasonably teach or suggest “A method for grading a tumor and/or for tumor prognosis comprising determining the level of the nucleic acid molecule of as defined in claim 1(J)(g) and/or the protein or peptide as defined in claim 1 in a sample obtained from a subject, wherein increased levels of the nucleic acid molecule as defined in claim 1(I)(g) and/or the protein or peptide as defined in claim 1 as compared to a control correlate with the a higher grade of the tumor and/or an adverse tumor prognosis” as required in claim 6.
Conclusion
No claim is allowed.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
If attempts to reach the examiner are unsuccessful, the examiner's supervisor, Tracy Vivlemore, can be reached on 571-272-2914.
The official fax number for this Group is (571) 273-8300.
Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638