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 .
Claims 1-4, 7, 14 have been canceled. Claim 15 has been added. Claims 5, 6, 8-13 and 15 are pending.
Applicant's arguments filed 6-29-26 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Please do not use bold face type in amendments. Just use underline and strike out.
Claim objections
Claims 5 and 6 contain excessive redundancies and are written unclearly. The preamble must be written more accurately. The steps must be written more accurately and clearly. The sample must be a mammal tumor sample. The structures being tested contain redundancies and must be written more succinctly, e.g. items a) and c) and f) are redundant because f) encompasses c) which encompasses a); items b) and d) and f) are redundant because f) encompasses d) which encompasses b). The meaning of item e) cannot be discerned.
The meaning of item f) cannot be discerned because it encompasses any single nucleotide or amino acid that occurs in SEQ ID NO: 1, 2, or 54 that is within any 250 nucleotide fragment. It does not require a 250 nucleotide fragment encoding any portion of SEQ ID NO: 1 or 54 or a 250 nucleotide fragment of SEQ ID NO: 2. Assuming it is intended to encompass a 250 nucleotide fragment of SEQ ID NO: 2, that concept is broader than items b) or d) and should be set forth (instead of items b) and d)?). It is unclear how the concept in f) applies to items a) and c).
The meaning of “wherein T is replaced by U in a) to f)” at the bottom of pg 2 cannot be discerned because the sample contains naturally occurring DNA comprising CGTA nucleotides.
The result of detecting the desired nucleic acid must be written more succinctly. E.g. A method of detecting the presence of a tumor in a mammal, the method comprising:
i) detecting the presence of a nucleic acid sequence:
a) encoding a protein that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1 or 54;
b) that is at least 95% identical to the nucleotide sequence of SEQ ID NO: 2
in a sample obtained from a mammal, wherein the presence of the nucleic acid sequence indicates the presence of a tumor in the mammal.
Claims 5 and 6 appear redundant except for the purpose which could be set forth in one claim, i.e. A method of detecting, grading, or prognosing a tumor (although none of them have adequate written description or enablement for reasons set forth below). Regardless, claim 6 has the same problems as claim 5 for reasons set forth above.
Claim 10 is redundant because a tumor is cancer. They are both uncontrolled growth of cells.
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 8-13 have been amended to be drawn to the method of claims 5 or 6 and have been combined with Group II.
Claims 5, 6, 8-13, 15 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.
Claim Rejections - 35 USC § 101
The rejection of claim 4 under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter has been withdrawn because the claim has been canceled.
Claim Rejections - 35 USC § 112
Claims 5, 6, 10-13 remain and claims 8, 9, 15 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 5 is drawn to a
PNG
media_image1.png
510
538
media_image1.png
Greyscale
(II) the protein or peptide is a protein or peptide encoded by the nucleic acid molecule of (I).
Claim 6 is drawn to
PNG
media_image2.png
592
544
media_image2.png
Greyscale
Claims 5 and 6 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”, or “adverse tumor prognosis”.
Claim 5 and 6 encompass using any fragment of at least 250 nucleotides of SEQ ID NO: 1, 2, 54 to do the same functions.
Claims 5 and 6 encompass using any protein encoded by the 250 nucleotide fragment of SEQ ID NO: 1, 2, 54.
Claims 5 and 6 encompass using HLA-H expression levels to detect, grade, or prognose any cancer, e.g. those set forth in claim 11 (breast, ovarian, endometrial, vaginal…leukemia cancer), claim 12 (bladder or ovarian cancer), or claim 13 (breast or ovarian cancer).
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 required in claims 5 and 6.
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”.
PNG
media_image3.png
192
410
media_image3.png
Greyscale
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 claims 5 and 6. There is nothing in this data for using HLA-H expression alone for diagnosing, grading, or prognosing a tumor as broadly encompassed by claims 5 and 6. 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 lacks written description for any sample from any subject as broadly encompassed by claims 5 and 6 other than a mammalian tumor sample. 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 correlate a mammalian sample to any plant, insect, invertebrate, fish, amphibian, reptile, or bird sample as broadly encompassed by claims 5 and 6.
The specification lacks written description for using any nucleotide sequence 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 5 and 6. 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 detecting, diagnosing, grading, or prognosing any tumor as required in claims 5 and 6.
The specification lacks written description for any using proteins encoded by such nucleic acids as broadly encompassed by item II of claims 5 and 6 for detecting, 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 detecting, diagnosing, grading, or prognosing any tumor as broadly encompassed by claims item II) of claims 5 and 6.
The specification fails to teach any sample with nucleic acids “wherein T is replaced by U in a) to f) as required in claims 5 and 6. The meaning is wholly unclear because tissue samples contain CGTA nucleotides. Therefore, the concept lacks written description.
The specification lacks written description for using the nucleotides or proteins of claim 5 or 6 to “monitor the non-efficacy” of any “tumor treatment” or “immunosuppressive therapy” as required in claims 8 and 9 for reasons set forth above. The specification fails to teach any levels of any HLA-A nucleotide or protein that correlates to efficacy or “non-efficacy” of any “tumor treatment” or “immunosuppressive therapy” as claimed. There is a complete lack of written description here.
The specification lacks written description for using HLA-H expression levels to diagnose, grade, or prognose any cancer as broadly encompassed by claims 5 and 6 or specifically set forth in claim 11 (breast, ovarian, endometrial, vaginal…leukemia cancer), claim 12 (bladder or ovarian cancer), or claim 13 (breast or ovarian cancer) for reasons set forth above.
The specification lacks written description for determining the level of nucleic acid or protein and comparing it to any sample from any subject who does not have a tumor, wherein the level of nucleic acid or protein is 1.5X greater indicates the presence of a tumor as required in claim 15. The concept is contemplated on pg 32, line 12, but there is nothing in the art or examples to support it. HLA-H (aka HLA-E) expression is not limited to tumors; it is normally expressed on many healthy nucleated cells, but its expression patterns and functional roles can differ in cancer tissues.
Normal physiological expression
HLA-E is a non-classical MHC class I molecule encoded by the HLA-E gene
PNG
media_image4.png
32
32
media_image4.png
Greyscale
Nature+1. Under healthy conditions, HLA class I molecules (including HLA-E) are expressed on the surface of virtually all nucleated cells in the body
PNG
media_image5.png
32
32
media_image5.png
Greyscale
GenDx. This is part of the immune system’s constant surveillance mechanism, presenting intracellular peptides to CD8⁺ cytotoxic T cells. HLA-E specifically can present peptides from stress-related proteins and interact with NK cell receptors, influencing immune tolerance and regulation
PNG
media_image4.png
32
32
media_image4.png
Greyscale
Nature+1. There is nothing in the examples or the art that says 1.5X increase in expression means the tissue sample is a tumor. Especially because HLA-H expression can be influenced or increased during certain immune and inflammatory states tied to infections, though the locus primarily functions as a non-functional or regulatory pseudogene/MHC class I-like molecule rather than a traditional surface antigen-presenting protein. [1, 2]
Key Details on HLA-H and Viral Response
Interferon Induction: Viral infections trigger the release of pro-inflammatory cytokines and interferons (such as type I and type II interferons), which can upregulate transcription linked to the HLA-H locus and its non-coding antisense RNAs (like HLA-H-AS1). [1]
Pseudogene Status: HLA-H contains a frameshift mutation preventing functional membrane-bound heavy chain surface expression, but its active transcripts participate in local gene regulation (such as repressing neighboring classical HLA-A). [1]
Viral Interference: Certain viruses (like Kaposi's Sarcoma-Associated Herpesvirus) have proteins that target the translated products or structural motifs of HLA-H for degradation, indicating that viral mechanisms interact with the wider MHC class I-like network during infection. [1]
Accordingly, claim 15 lacks written description.
In summary, the specification fails to adequately describe how to use HLA-H expression to detect, diagnose, grade, or prognose a tumor in any sample from any subject as broadly encompassed by the claims.
Response to arguments
Applicants argue “the preferred embodiments are just that – they are the most preferred” (pg 7). Applicants’ argument is not persuasive because it fails to address the lack of written description in the specification for the amount of nucleotide sequence encoding HLA-H or HLA-H protein that correlates to the detection of any tumor (in any sample from any subject). Nor does is address the amount of HLA-H nucleotides or amino acids that correlate to grading or prognosing any tumor (in any sample from any subject).
Applicants discussion of the role of HLA-H as an immunosuppressant (pg 8) is noted but is not persuasive because it fails to address the issues at hand.
Applicants point to Examples 1-4 which are not persuasive for reasons set forth in the rejection. They do not teach the amount of nucleotide sequence encoding HLA-H or HLA-H protein that correlates to the detection of any tumor (in any sample from any subject) as required in claim 5. They do not teach the amount of HLA-H nucleotides or amino acids that correlate to grading or prognosing any tumor (in any sample from any subject) as required in claim 6.
Applicants point to pg 32, lines 14-16, through pg 39, line 3, which teaches HLA-H is not detected in healthy patients and was detected in all tumor patients (pg 8-9). Applicants’ argument is not persuasive because the presence of HLA-H is not limited to the presence of tumors.
Is HLA-H Expression Limited to Tumors?
No — HLA-H (HLA-E) is not limited to tumors; it is normally expressed on many healthy nucleated cells, but its expression patterns and functional roles can differ in cancer tissues.
Normal physiological expression
HLA-E is a non-classical MHC class I molecule encoded by the HLA-E gene
PNG
media_image4.png
32
32
media_image4.png
Greyscale
Nature+1. Under healthy conditions, HLA class I molecules (including HLA-E) are expressed on the surface of virtually all nucleated cells in the body
PNG
media_image5.png
32
32
media_image5.png
Greyscale
GenDx. This is part of the immune system’s constant surveillance mechanism, presenting intracellular peptides to CD8⁺ cytotoxic T cells. HLA-E specifically can present peptides from stress-related proteins and interact with NK cell receptors, influencing immune tolerance and regulation
PNG
media_image4.png
32
32
media_image4.png
Greyscale
Nature+1.
Claims 5, 6, 10-13 remain and claims 8, 9, 15 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 in a mammalian tissue sample, does not reasonably provide enablement for using expression level of HLA-H as a means of diagnosing, grading, or prognosing tumors or doing so in any sample from any subject. 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.
Claims 5 and 6 and their scopes are recited above.
The teachings in the specification and their deficiencies are discussed above.
The specification does not enable using any sample from any subject as broadly encompassed by claims 5 and 6 other than a mammalian tumor sample. 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 correlate a mammalian sample to any plant, insect, invertebrate, fish, amphibian, reptile, or bird sample as broadly encompassed by claims 5 and 6.
The specification does not enable using any nucleotide sequence 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 5 and 6. 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 detecting, diagnosing, grading, or prognosing any tumor as required in claims 5 and 6.
The specification does not enable using proteins encoded by such nucleic acids as broadly encompassed by item II of claims 5 and 6 for detecting, 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 detecting, diagnosing, grading, or prognosing any tumor as broadly encompassed by claims item II) of claims 5 and 6.
The specification fails to teach any sample with nucleic acids “wherein T is replaced by U in a) to f) as required in claims 5 and 6. The meaning is wholly unclear because tissue samples contain CGTA nucleotides. Therefore, the concept is not enabled.
The specification does not enable using the nucleotides or proteins of claim 5 or 6 to “monitor the non-efficacy” of any “tumor treatment” or “immunosuppressive therapy” as required in claims 8 and 9 for reasons set forth above. The specification fails to teach any levels of any HLA-A nucleotide or protein that correlates to efficacy or “non-efficacy” of any “tumor treatment” or “immunosuppressive therapy” as claimed. There is a complete lack of enablement here.
The specification does not enable using HLA-H expression levels to diagnose, grade, or prognose any cancer as broadly encompassed by claims 5 and 6 or specifically set forth in claim 11 (breast, ovarian, endometrial, vaginal…leukemia cancer), claim 12 (bladder or ovarian cancer), or claim 13 (breast or ovarian cancer) for reasons set forth above.
The specification does not enable determining the level of nucleic acid or protein and comparing it to any sample from any subject who does not have a tumor, wherein the level of nucleic acid or protein is 1.5X greater indicates the presence of a tumor as required in claim 15. The concept is contemplated on pg 32, line 12, but there is nothing in the art or examples to support it. HLA-H (aka HLA-E) expression is not limited to tumors; it is normally expressed on many healthy nucleated cells, but its expression patterns and functional roles can differ in cancer tissues.
Normal physiological expression
HLA-E is a non-classical MHC class I molecule encoded by the HLA-E gene
PNG
media_image4.png
32
32
media_image4.png
Greyscale
Nature+1. Under healthy conditions, HLA class I molecules (including HLA-E) are expressed on the surface of virtually all nucleated cells in the body
PNG
media_image5.png
32
32
media_image5.png
Greyscale
GenDx. This is part of the immune system’s constant surveillance mechanism, presenting intracellular peptides to CD8⁺ cytotoxic T cells. HLA-E specifically can present peptides from stress-related proteins and interact with NK cell receptors, influencing immune tolerance and regulation
PNG
media_image4.png
32
32
media_image4.png
Greyscale
Nature+1. There is nothing in the examples or the art that says 1.5X increase in expression means the tissue sample is a tumor. Especially because HLA-H expression can be influenced or increased during certain immune and inflammatory states tied to infections, though the locus primarily functions as a non-functional or regulatory pseudogene/MHC class I-like molecule rather than a traditional surface antigen-presenting protein. [1, 2]
Key Details on HLA-H and Viral Response
Interferon Induction: Viral infections trigger the release of pro-inflammatory cytokines and interferons (such as type I and type II interferons), which can upregulate transcription linked to the HLA-H locus and its non-coding antisense RNAs (like HLA-H-AS1). [1]
Pseudogene Status: HLA-H contains a frameshift mutation preventing functional membrane-bound heavy chain surface expression, but its active transcripts participate in local gene regulation (such as repressing neighboring classical HLA-A). [1]
Viral Interference: Certain viruses (like Kaposi's Sarcoma-Associated Herpesvirus) have proteins that target the translated products or structural motifs of HLA-H for degradation, indicating that viral mechanisms interact with the wider MHC class I-like network during infection. [1]
Accordingly, claim 15 is not enabled.
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 detect, diagnose, grade, or prognose a tumor in any sample from any subject as broadly encompassed by the claims.
Response to arguments
Applicants’ arguments are essentially the same as those above in the written description rejection and are not persuasive for reasons set forth above.
Claims 5, 6, 10-13 remain and claims 8, 9, 15 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.
The steps and structures in claims 5 and 6 are so confusing that the metes and bounds of the steps and what is being tested are indefinite:
Items a) and c) and f) are redundant because f) encompasses c) which encompasses a). Items b) and d) and f) are redundant because f) encompasses d) which encompasses b). The meaning of item e) cannot be discerned.
The meaning of item f) cannot be discerned because it encompasses any single nucleotide or amino acid that occurs in SEQ ID NO: 1, 2, or 54 that is within any 250 nucleotide fragment. It does not require a 250 nucleotide fragment encoding any portion of SEQ ID NO: 1 or 54 or a 250 nucleotide fragment of SEQ ID NO: 2. Assuming it is intended to encompass a 250 nucleotide fragment of SEQ ID NO: 2, that concept is broader than items b) or d) and should be set forth (instead of items b) and d)?). It is unclear how the concept in f) applies to items a) and c).
There is nothing in claims 5 or 6 (or the specification) that says when the amount of HLA-A nucleotide or protein indicates the presence, grade, or prognosis of a tumor as required in claims 5 and 6 which is essential to the invention.
The meaning of “wherein T is replaced by U in a) to f)” at the bottom of pg 2 cannot be discerned because the sample contains naturally occurring DNA comprising CGTA nucleotides.
There is nothing in claims 8 or 9 (or the specification) that says when the amount of HLA-A nucleotide or protein indicates the “non-efficacy” of a tumor treatment or immunosuppressive therapy of a tumor which is essential to the invention.
Claim 10 does not further limit claim 5 or 6 because a tumor is cancer. They are both uncontrolled growth of cells.
Response to arguments
Applicants point to pg 32, lines 14-16, which are not persuasive for reasons set forth above. Applicants argue the amendment overcomes the rejection which is not persuasive for reasons set forth above.
Claim Rejections - 35 USC § 102
The rejection of claim 7 under 35 U.S.C. 102a1 as being anticipated by Betsholtz (20060216722) has been withdrawn because the claim has been canceled.
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.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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
Prosecution Insights