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 .
Election/Restrictions
Applicant’s election of Group II (Claims 4-5; drawn to an ex vivo or in vitro method for increasing the likelihood of a fertilized oocyte or preimplantation embryo to become implanted during in vitro fertilization) in the reply filed on January 5, 2026, is acknowledged.
As claims 2 and 14 are now dependent on claim 4, they are now considered to also be a part of Group II.
Applicant further elected the following species:
a. proteins/peptide structures
DETAILED ACTION
The amended claims filed on June 29, 2026, have been acknowledged. Claims 1, 3, and 6-13 were cancelled. Claims 2, 4, and 14 were amended. Claims 2, 4-5, and 14 are pending and examined on the merits.
Priority
The applicant claims foreign priority from EP19205450.0 filed on October 10, 2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55, received April 25, 2022. Claims 2, 4-5, and 14 find support in foreign application EP19205450.0 filed on October 10, 2019.
Information Disclosure Statement
The information disclosure statement (IDS) filed on April 10, 2026, has been considered.
New Claim Rejections - 35 USC § 112
Claims 2, 4-5, and 14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification and the prior art, while being enabling for supplementing the media with soluble HLA-G, does not reasonably provide enablement for increasing the likelihood of implantation by increasing the amount of HLA-H, HLA-J, HLA-L, HLA-V, HLA-E, HLA-F without also increasing the amount of soluble HLA-G. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The applicant’s disclosure does not provide enough information for any person skilled in the art to increase the likelihood of implantation by increasing the amount of HLA-H, HLA-J, HLA-L, HLA-V, HLA-E, HLA-F without also increasing the amount of soluble HLA-G. This is a new rejection made in response to Applicant’s amendments to the claims.
The factors to be weighed to evaluate whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is undue are set forth in MPEP 2164.01(a).
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Although all the factors have been considered, the relevant factors will be addressed below.
Breadth of the claims: Claim 4 recites the following claim language An ex vivo or in vitro method for increasing the likelihood of a fertilized oocyte or preimplantation embryo of becoming implanted during in vitro fertilization of a female comprising supplementing cell culture medium with at least one nucleic acid molecule, vector, host cell, or protein or peptide, or any combination product thereof selected from (I)-(IV), and culturing an isolated oocyte or preimplantation embryo in the cell culture medium, wherein culturing the supplemented cell culture increases the amount of HLA-H, HLA-J, HLA-L, HLA-V, HLA-E, HLA-F and/or HLA-G in the isolated oocyte or preimplantation embryo at the time it is transferred to the uterus of the female which increases receptiveness of the uterus for the isolated oocyte or preimplantation embryo”. The broadest reasonable interpretation is that any of the nucleic acid molecules, vectors, host cells, or proteins or peptides, selected from (I)-(IV) individually or in any combination can be supplemented in IVF culture media to increase the amount of HLA-H, HLA-J, HLA-L, HLA-V, HLA-E, HLA-F and/or HLA-G and that this will increase the likelihood of a fertilized oocyte or preimplantation embryo of becoming implanted during in vitro fertilization.
Nature of the invention: The subject matter of the invention relates to a method of increasing the likelihood of a fertilized oocyte or preimplantation embryo of becoming implanted during in vitro fertilization of a female comprising supplementing cell culture medium and culturing an isolated oocyte or preimplantation embryo in the cell culture medium.
State of the prior art: The prior art teaches that soluble HLA-G improves implantation rate as identified by United States Patent Application No. 20050241013 (Sher) and Uniprot (P17693 · HLAG_HUMAN).
Sher teaches that soluble HLA-G (shLA-G) has been isolated from
the culture media surrounding embryos and blastocysts. The absence of sHLA-G from human embryo culture media is associated with reduced embryo development and pregnancy rates. They sought to determine whether expression of sHLA-G in media surrounding individually cultured embryos could be used as a “marker, that could predict
subsequent IVF outcome. The media surrounding 397 individual ICSI-derived embryos in 106 women (26-43 years, mean=36.9+5.8) were evaluated for SHLA-G expression. Thirty eight of the 102 patients (37%) achieved one or more ultrasound confirmed clinical pregnancies. Group 1 (n=49) had at least one embryo transferred (mean=3.1) that tested “positive” for shLA-G. The clinical pregnancy and implantation rate per ET were 78% and 36%, respectively. The multiple pregnancy rate was 10% when only one shLA-G “positive” embryo was transferred and, 32% when more were transferred. In Group 2 (n=53) none of the embryos transferred (mean=3.2) tested “positive” for sHLA-G. Six had clinical pregnancies 11%. The implantation rate per ET was 7% (paragraphs 0012-0015). Sher specifically identifies a method of adding sHLA-G to the medium in which embryos are cultured and/or delivered into the uterine environment through embryo transfer to enhance implantation and pregnancy potential of those embryos (paragraphs 0029-0031 and claim 1).
Uniprot (P17693 · HLAG_HUMAN) evidences that the consensus wild type sequence for human soluble HLA-G (also known as HLA-G5) is 99.4% similar to SEQ ID NO: 15 (page 11).
The prior art identifies HLA-E and HLA-F as also being expressed at the fetal-maternal interference and suggests a role, in combination with HLA-G, in maintaining immune tolerance of the against the paternal antigens of the fetus during pregnancy, as identified by Shaikly et al. (Reproductive BioMedicine Online 20: 223– 233. 2010) and Ishitani et al. (The Journal of Immunology 171: 1376–1384. 2003).
Shaikly teaches that HLA-E is known to bind with CD94/NKG2A inhibitory receptors on uterine natural killer cells, thus providing protection for trophoblast cells from NK cytotoxicity. Cell-surface HLA-E expression is dependent on the co-expression of HLA-G, thus their concomitant cell-surface expression may provide immunoprotection of the fetus from the maternal immune system. Although the expression of HLA-G has been reported in human embryos, no detailed studies have been conducted regarding HLA-E protein expression. In one study, Cao et al. (1999) reported HLA-E mRNA in 84% of preimplantation embryos analysed. The colocalization of HLA-E and HLA-G clusters indicates that these receptors may function together at the cell surface to bind receptors with increased avidity and enhance inhibitory function. The marked expression of HLA-E and HLA-G on blastocysts graded as good quality and therefore associated with high implantation potential (whole document).
Ishitani teaches that to examine the role of all three nonclassical class I Ags in the maternal immune response during pregnancy, they developed mAbs specific for the membrane HLA-G, sHLA-G, HLA-E, and HLA-F, and used these mAbs in a comprehensive examination of protein expression in placental tissues. To gain
further insight into the function of these molecules, they examined peptides bound to both sHLA-G and mHLA-G isolated directly from placenta, data that confirm the previously described HLA-G peptide binding motif, but indicate a peptide profile distinct from that found in transfected cell lines. Further, HLA-E was found in all cells that expressed either form of HLA-G, indicating that HLA-E is indeed complexed with the HLA-G signal sequence derived nonamer in these cells. Finally, using new reagents specific for HLA-F, a restricted pattern of expression was observed, primarily on extravillous trophoblasts that had invaded the maternal decidua. Comparative staining of these cells indicated that HLA-F was on the surface of these cells, defining these cells as the first normal cell type to demonstrate surface expression of this Ag. The finding that the third nonclassical Ag, HLA-F, is also expressed in the placenta adds to both the growing knowledge of class I expression in this special immune environment and addresses the beginnings of our understanding of HLA-F function. Although it is not yet clear what role HLA-F plays in the immune response, it has long been reported that the gene is differentially expressed in immune cells. The observation that HLA-F is expressed primarily in trophoblasts that have invaded the maternal decidua, and that these same cells simultaneously express HLA-E and G, provides the first example of cells that express all three nonclassical class I Ags simultaneously. The fact that these cells are directly implanted in the maternal decidua in direct contact with maternal immune cells is further suggestive that all three Ags are essential for maternal accommodation of the foreign allograft that this stage of human life represents. Whereas early investigations of HLA expression in human placental tissue led to the hypotheses of HLA-G as a key element in this accommodation, it now appears that the other two nonclassical Ags may also be essential. In addition, specific peptide binding in HLA-G and indeed the specificity of the nonamer peptide that HLA-G uniquely makes available to HLA-E offer clear evidence of interactions and synergy between these molecules (whole document).
Level of predictability in the art: The prior art has identified that soluble HLA-G is known to be associated with increased implantation rates when expressed and contemplates supplementing culture media with soluble HLA-G to improve implantation rates. The prior art does identify that HLA-E and HLA-G expression is associated with blastocysts graded as good quality and therefore associated with high implantation potential. The prior art also identifies the potential importance of HLA-E and HLA-F in maintaining immune tolerance during pregnancy but has not contemplated supplementing the media HLA-E or HLA-F to improve implantation potential. The prior art has not identified any role of HLA-H, HLA-J, HLA-L, or HLA-V in the maintenance of immune tolerance during pregnancy. As such, this results in unpredictability about how someone can add any of HLA-H, HLA-J, HLA-L, HLA-V, HLA-E, or HLA-F individually or in combination with each other without also including soluble HLA-G to improve the likelihood of implantation as soluble HLA-G is the only molecule that has been identified to be directly implicated in implantation efficacy when it is expressed.
Amount of direction provided by the inventor and existence of working examples: The specification discloses that HLA-G, HLA-H, HLA-J, HLA-L, HLA-V, HLA-V, HLA-Y, HLA-E, and/or HLA-F was added to embryo cell culture, that HLA-H, HLA-J, HLA-L, HLA-V, HLA-V, HLA-Y, HLA-E, HLA-F and HLA-G were found to be expressed
in blastocyte cell culture, and that implantation rates, as well as successful pregnancies were significantly higher from embryos receiving the HLA supplementation treatment as compared to the control group (Examples 1-2). As the examples only recite that HLA-G, HLA-H, HLA-J, HLA-L, HLA-V, HLA-V, HLA-Y, HLA-E, and/or HLA-F was added to embryo cell culture, it is not clear which HLA compound or combination of compounds were actually added to the culture media that produced the increase in implantation rates and successful pregnancies. Furthermore, it is unclear how the HLA compound(s) were added to the media (i.e. was it in a vector, as a nucleic acid or protein, or part of a host cell) and which nucleic acid or amino acid sequence was used as Applicant has identified seven isoforms for HLA-G (SEQ ID NOs: 11-17) and three isoforms for HLA-F (SEQ ID NOs: 8-10), let alone any of the other possible sequences that fall under the at least 85% sequence similarity claim limitation.
Therefore, as it is unclear what HLA molecules were added and how they were added, this would require trial and error experimentation to identify the HLA molecule(s) (specific sequences, specific individual molecules and combinations, and specific delivery modes) that improve implantation and successful pregnancy rate.
Quantity of experimentation needed: In light of the above factors, the prior art provides enablement for supplementing culture media with at least soluble HLA-G during embryo culture to improve implantation rate but not any one of HLA-H, HLA-J, HLA-L, HLA-V, HLA-E, HLA-F and non-soluble HLA-G isoforms individually or in any combination that does not also increase soluble HLA-G levels as soluble HLA-G is the only known HLA compound whose expression has been directly identified as being important for increasing implantation rate. As such, there would be undue experimentation related to using any of the HLA-H, HLA-J, HLA-L, HLA-V, HLA-E, HLA-F and non-soluble HLA-G isoforms individually or in any combination that does not also increase soluble HLA-G levels to practice the full scope of the claim.
Claims 2, 5, and 14 are also rejected because of their dependency on claim 4.
Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be weighed to evaluate whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is undue are set forth in MPEP 2164.01(a).
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Although all the factors have been considered, the relevant factors will be addressed below.
Breadth of the claims: Claim 4 recites the following claim language An ex vivo or in vitro method for increasing the likelihood of a fertilized oocyte or preimplantation embryo of becoming implanted during in vitro fertilization of a female comprising supplementing cell culture medium with at least one nucleic acid molecule, vector, host cell, or protein or peptide, or any combination product thereof selected from (I)-(IV), and culturing an isolated oocyte or preimplantation embryo in the cell culture medium, wherein culturing the supplemented cell culture increases the amount of HLA-H, HLA-J, HLA-L, HLA-V, HLA-E, HLA-F and/or HLA-G in the isolated oocyte or preimplantation embryo at the time it is transferred to the uterus of the female which increases receptiveness of the uterus for the isolated oocyte or preimplantation embryo”. Claim 14 narrows the supplement to HLA-H, HLA-J, HLA-L soluble, HLA-L membrane bound, HLA-V, and HLA-Y (corresponds to SEQ ID NOs 1-6, respectively). The broadest reasonable interpretation is that any of HLA-H, HLA-J, HLA-L soluble, HLA-L membrane bound, HLA-V, and HLA-Y individually or in any combination can be supplemented in IVF culture media to increase the amount of HLA-H, HLA-J, HLA-L, HLA-V, HLA-E, HLA-F and/or HLA-G and that this will increase the likelihood of a fertilized oocyte or preimplantation embryo of becoming implanted during in vitro fertilization.
Nature of the invention: The subject matter of the invention relates to a method of increasing the likelihood of a fertilized oocyte or preimplantation embryo of becoming implanted during in vitro fertilization of a female comprising supplementing cell culture medium and culturing an isolated oocyte or preimplantation embryo in the cell culture medium.
State of the prior art: The prior art teaches that soluble HLA-G improves implantation rate as identified by United States Patent Application No. 20050241013 (Sher) and Uniprot (P17693 · HLAG_HUMAN).
Sher teaches that soluble HLA-G (shLA-G) has been isolated from
the culture media surrounding embryos and blastocysts. The absence of sHLA-G from human embryo culture media is associated with reduced embryo development and pregnancy rates. They sought to determine whether expression of sHLA-G in media surrounding individually cultured embryos could be used as a “marker, that could predict
subsequent IVF outcome. The media surrounding 397 individual ICSI-derived embryos in 106 women (26-43 years, mean=36.9+5.8) were evaluated for SHLA-G expression. Thirty eight of the 102 patients (37%) achieved one or more ultrasound confirmed clinical pregnancies. Group 1 (n=49) had at least one embryo transferred (mean=3.1) that tested “positive” for shLA-G. The clinical pregnancy and implantation rate per ET were 78% and 36%, respectively. The multiple pregnancy rate was 10% when only one shLA-G “positive” embryo was transferred and, 32% when more were transferred. In Group 2 (n=53) none of the embryos transferred (mean=3.2) tested “positive” for sHLA-G. Six had clinical pregnancies 11%. The implantation rate per ET was 7% (paragraphs 0012-0015). Sher specifically identifies a method of adding sHLA-G to the medium in which embryos are cultured and/or delivered into the uterine environment through embryo transfer to enhance implantation and pregnancy potential of those embryos (paragraphs 0029-0031 and claim 1).
Uniprot (P17693 · HLAG_HUMAN) evidences that the consensus wild type sequence for human soluble HLA-G (also known as HLA-G5) is 99.4% similar to SEQ ID NO: 15 (page 11).
The prior art identifies HLA-E and HLA-F as also being expressed at the fetal-maternal interference and suggests a role, in combination with HLA-G, in maintaining immune tolerance of the against the paternal antigens of the fetus during pregnancy, as identified by Shaikly et al. (Reproductive BioMedicine Online 20: 223– 233. 2010) and Ishitani et al. (The Journal of Immunology 171: 1376–1384. 2003).
Shaikly teaches that HLA-E is known to bind with CD94/NKG2A inhibitory receptors on uterine natural killer cells, thus providing protection for trophoblast cells from NK cytotoxicity. Cell-surface HLA-E expression is dependent on the co-expression of HLA-G, thus their concomitant cell-surface expression may provide immunoprotection of the fetus from the maternal immune system. Although the expression of HLA-G has been reported in human embryos, no detailed studies have been conducted regarding HLA-E protein expression. In one study, Cao et al. (1999) reported HLA-E mRNA in 84% of preimplantation embryos analysed. The colocalization of HLA-E and HLA-G clusters indicates that these receptors may function together at the cell surface to bind receptors with increased avidity and enhance inhibitory function. The marked expression of HLA-E and HLA-G on blastocysts graded as good quality and therefore associated with high implantation potential (whole document).
Ishitani teaches that to examine the role of all three nonclassical class I Ags in the maternal immune response during pregnancy, they developed mAbs specific for the membrane HLA-G, sHLA-G, HLA-E, and HLA-F, and used these mAbs in a comprehensive examination of protein expression in placental tissues. To gain
further insight into the function of these molecules, they examined peptides bound to both sHLA-G and mHLA-G isolated directly from placenta, data that confirm the previously described HLA-G peptide binding motif, but indicate a peptide profile distinct from that found in transfected cell lines. Further, HLA-E was found in all cells that expressed either form of HLA-G, indicating that HLA-E is indeed complexed with the HLA-G signal sequence derived nonamer in these cells. Finally, using new reagents specific for HLA-F, a restricted pattern of expression was observed, primarily on extravillous trophoblasts that had invaded the maternal decidua. Comparative staining of these cells indicated that HLA-F was on the surface of these cells, defining these cells as the first normal cell type to demonstrate surface expression of this Ag. The finding that the third nonclassical Ag, HLA-F, is also expressed in the placenta adds to both the growing knowledge of class I expression in this special immune environment and addresses the beginnings of our understanding of HLA-F function. Although it is not yet clear what role HLA-F plays in the immune response, it has long been reported that the gene is differentially expressed in immune cells. The observation that HLA-F is expressed primarily in trophoblasts that have invaded the maternal decidua, and that these same cells simultaneously express HLA-E and G, provides the first example of cells that express all three nonclassical class I Ags simultaneously. The fact that these cells are directly implanted in the maternal decidua in direct contact with maternal immune cells is further suggestive that all three Ags are essential for maternal accommodation of the foreign allograft that this stage of human life represents. Whereas early investigations of HLA expression in human placental tissue led to the hypotheses of HLA-G as a key element in this accommodation, it now appears that the other two nonclassical Ags may also be essential. In addition, specific peptide binding in HLA-G and indeed the specificity of the nonamer peptide that HLA-G uniquely makes available to HLA-E offer clear evidence of interactions and synergy between these molecules (whole document).
The prior art identifies that embryo culture media can negatively impact the likelihood of implantation and successful pregnancy, as identified by Mantikou et al. (Human Reproduction Update 19: 210–220. 2013).
Mantikou discloses that the media composition used for culturing embryos prior to embryo transfer can have an important effect on implantation and successful pregnancy rate as the G2 cultur medium from VitroLife showed significantly less pregnancy rates compared to four other media compositions (Sydney IVF, MultiBlast, EllioStep2, and GM501). As such, the media composition used can have important effect on implantation and successful pregnancy rate (whole document).
Level of predictability in the art: The prior art has identified that soluble HLA-G is known to be associated with increased implantation rates when expressed and contemplates supplementing culture media with soluble HLA-G to improve implantation rates. The prior art does identify that HLA-E and HLA-G expression is associated with blastocysts graded as good quality and therefore associated with high implantation potential. The prior art also identifies the potential importance of HLA-E and HLA-F in maintaining immune tolerance during pregnancy but has not contemplated supplementing the media HLA-E or HLA-F to improve implantation potential. The prior art has not identified any role of HLA-H, HLA-J, HLA-L, or HLA-V in the maintenance of immune tolerance during pregnancy. Furthermore, the prior art has identified that the media composition is important for increasing implantation rate as G2 was found to reduce the chances of implantation and successful pregnancy. As such, this results in unpredictability about how someone can add any of HLA-H, HLA-J, HLA-L, and HLA-V, individually or in combination with each other without also including soluble HLA-G to improve the likelihood of implantation as soluble HLA-G is the only molecule that has been identified to be directly implicated in implantation efficacy when it is expressed.
Amount of direction provided by the inventor and existence of working examples: The specification discloses that HLA-G, HLA-H, HLA-J, HLA-L, HLA-V, HLA-V, HLA-Y, HLA-E, and/or HLA-F was added to embryo cell culture, that HLA-H, HLA-J, HLA-L, HLA-V, HLA-V, HLA-Y, HLA-E, HLA-F and HLA-G were found to be expressed
in blastocyte cell culture, and that implantation rates, as well as successful pregnancies were significantly higher from embryos receiving the HLA supplementation treatment as compared to the control group (Examples 1-2). As the examples only recite that HLA-G, HLA-H, HLA-J, HLA-L, HLA-V, HLA-V, HLA-Y, HLA-E, and/or HLA-F was added to embryo cell culture, it is not clear which HLA compound or combination of compounds were actually added to the culture media that produced the increase in implantation rates and successful pregnancies. Furthermore, it is unclear how the HLA compound(s) were added to the media (i.e. was it in a vector, as a nucleic acid or protein, or part of a host cell) and which nucleic acid or amino acid sequence was used as Applicant has identified seven isoforms for HLA-G (SEQ ID NOs: 11-17) and three isoforms for HLA-F (SEQ ID NOs: 8-10), let alone any of the other possible sequences that fall under the at least 85% sequence similarity claim limitation.
Therefore, as it is unclear what HLA molecules were added and how they were added, this would require trial and error experimentation to identify the HLA molecule(s) (specific sequences, specific individual molecules and combinations, and specific delivery modes) that improve implantation and successful pregnancy rate.
Quantity of experimentation needed: In light of the above factors, the prior art provides identifies that supplementing culture media with soluble HLA-G during embryo culture can improve implantation rate but has not identified that HLA-H, HLA-J, HLA-L, and HLA-V have any role of modulating immune tolerance during pregnancy. As such, there would be undue experimentation related to using any of the HLA-H, HLA-J, HLA-L, and HLA-V individually to increase implantation rate as none of these molecules, in the art and in the instant application, have been shown to be capable of this.
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of claims 4-5 under 35 U.S.C. 102(a)(1) as being anticipated by Fuzzi et al. (Eur. J. Immunol. 32: 311–315. 2002), as evidenced by Uniprot (P17693 · HLAG_HUMAN) and Jurisicova et al. (Proc. Natl. Acad. Sci. USA 93: 161-165. 1996) is withdrawn in light of Applicant’s amendments to the claims to require supplementation of the culture medium with the HLA compounds.
New 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 2 and 4-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by World Intellectual Property Organization Patent Application No. 2013078312 (Feskov; referenced in IDS), as evidenced by Uniprot (P17693 · HLAG_HUMAN). This is a new rejection made in response to Applicant’s amendments to the claims.
Feskov teaches a method of supplementing an embryo culture media with s-HLA-G, with a preferred concentration measurement in the embryo transfer medium in the range of 0.175 to 0.350 optical density (OD). The s-HLA-G is added to the embryo transfer medium, and the embryo is then cultured in said medium, for 5 to 20 minutes, and more preferably for approximately 10 minutes immediately prior to transfer of the embryo into the uterus. Feskov teaches that oocytes or embryos can be transferred to the patient for inception
Feskov specifically identifies that the !VF-derived oocytes or embryos are grown on suitable culture medium and in addition to the use of commonly available culture media for embryo preparation, the method of the invention can be combined with other techniques in order to increase the probability and success of pregnancy inception (such as sHLA-G supplementation) (page 8, line 26-page 9, line 17, page 16, line 24-page 19, line 13, page 30, lines 18-24, page 34, lines 7-27).
Uniprot (P17693 · HLAG_HUMAN) evidences that the consensus wild type sequence for human soluble HLA-G (also known as HLA-G5) is 99.4% similar to SEQ ID NO: 15 (page 11).
Conclusion
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.
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/KEENAN A BATES/Examiner, Art Unit 1631
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