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 .
Priority
The present application was filed on 08/18/2022. Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT/JP2021/045799, filed on 12/13/2021. This application claims benefit of the foreign Application JAPAN 2021-000399 filed 01/05/2021 and JAPAN 2021-139495 filed 08/30/2021.
Claim status
Claims 1-6, 8-9 and 11 are pending and examined.
Drawings
The drawings are objected to because:
Fig.3, x axis labels are not clear;
Fig.4, the title is not clearly shown;
Fig.7, y axis title covers y axis labels.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 3-6, and 11 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 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 breadth of the claim
Claims 3 and 11 encompass the measurement of the soluble CD163 concentration in a human body fluid for determining fertility of an ovum, or an embryo that develops from an ovum after fertilization.
The nature of the invention
The fertility of an ovum, or an embryo that develops from an ovum after fertilization is determined if the level of soluble CD163 in a body fluid from a human is higher than a standard value, wherein the standard value is a soluble CD163 concentration in a body fluid of another human whose pregnancy did not establish after transfer of an embryo that develops from a human ovum after fertilization. It is noted that the fertility in the invention means the level of the ability of an ovum, or an embryo that develops from an ovum after fertilization, to achieve the entire process from implantation to pregnancy (see Specification par.23).
The state of the prior art:
Diao (Development of a new endometrial immune cell-based score (EI-score) for the prediction of implantation outcomes for patients undergoing IVF/IC, Placenta 99 (2020) 180–188) discloses an EI-score for predicting implantation success for the patients who received in vitro fertilization, wherein the score includes CD163 + M2-macrophage. However, the score is based on the expression of endometrial immune cell markers in the endometrial tissues, but not based on the presence of soluble CD163 markers in the body fluid (see page 181 section 2.3). Moreover, Diao shows that the expression of CD163 + M2-macrophage was elevated in the implantation failure group. While Diao discloses the association of CD163 with the implantation success in the patients (i.e., the fertility of an embryo), Diao does not teach measuring a concentration of soluble CD163 marker in the body fluid, or the level of soluble CD163 is higher in the implantation success group than that in the implantation failure group.
Vogel (Preterm delivery predicted by soluble CD163 and CRP in women with symptoms of preterm delivery, an International Journal of Obstetrics and Gynaecology 112, pp. 737–742, 2005) teaches that a soluble form of CD163 (sCD163) has been identified in plasma and can be used as a predictor of preterm delivery (see Abstract, see page 737 col.2 par.2). While Vogel teaches measuring a concentration of soluble CD163 marker in the body fluid, it is not used for determining the ability of an ovum, or an embryo that develops from an ovum after fertilization, to achieve the entire process from implantation to pregnancy (i.e., fertility).
The level of predictability in the art:
Diao teaches that the level of CD163 in conjunction with M2-macrophage is known for predicting the implantation success in the patients. While “predicting the implantation success in the patients” is in line with predicting fertility within the scope of the claim, the prior art does not teach measuring soluble CD163 and using the measured level to predict fertility of an ovum, or an embryo that develops from an ovum after fertilization in the patient.
Vogel teaches that the level of soluble CD163 is known as a predictor of preterm delivery. However, predicting preterm delivery does not equate predicting the success or failure of the process from implantation to pregnancy. In fact, when a woman gives birth, whether the baby is full-term or preterm, it indicates that the implantation of the embryo in the woman was successful, and the woman was pregnant. Vogel does not disclose that the level of soluble CD163 is used to predict fertility within the scope of the claim because the process from implantation to pregnancy is always successful in women with preterm or full-term delivery and thus fertility is presumed to be present.
Therefore, the use of soluble CD163 to predict fertility within the scope of the claim is not predictable. It is unreasonable to presume that a higher concentration of soluble CD163 marker in the body fluid than a standard value is determined for the high fertility subject.
The presence of working examples:
Examples 1-4 in the Specification compare the concentration of soluble CD163 marker in the body fluid from subjects in the pregnancy positive group and subjects in the pregnancy negative group. Examples 1 and 2 show the concentration of soluble CD163 marker in follicular fluid. Example 3 shows the concentration of soluble CD163 marker in the sera. Example 4 shows the concentration of soluble CD163 marker in follicular fluid and sera. While the median concentration of the soluble CD163 marker in the pregnancy negative group was lower than the median concentration of the soluble CD163 marker in the pregnancy positive group in all four examples, the p values of examples 1 and 3 were 0.1274 and 0.08, respectively. These p values would lead to accepting a 12% or 8% probability that the data supports the null hypothesis that there is no difference in the concentration of the soluble CD163 marker between the compared groups. According to the default P value in most scientific research, e.g., P value =0.05, the larger p value (e.g., p >0.05) shows the lower probability of the concentration of the soluble CD163 marker that supports the difference between the compared groups the P, so the differences were not statistically significant.
Therefore, the data in the specification are not sufficient to demonstrate that a subject has high fertility if the concentration of soluble CD163 is higher than a standard value.
The quantity of experimentation necessary:
It would be undue experimentation for a skilled artisan to make and use the inventions as claimed, since there is no support from prior art that the concentration of soluble CD163 in the pregnancy positive group is higher than that in the pregnancy negative group. The amount of experimentation in the disclosure would not be reasonable because it does not show a significant difference in the concentration of soluble CD163 between the two groups.
The level of ordinary skill in the art:
The level of skill in the art of diagnosing and treating infertility in a subject is high, as an ordinary person in this art needs specialized knowledge of immunological factors that contribute to implantation success of a woman’s uterus.
In summary, there is a lack of disclosure in the art as well as in the specification as to a correlation between the elevated level of soluble CD163 markers and high fertility of an ovum or an embryo that develops from an ovum after fertilization. Thus, 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 claims 3-6 and 11.
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 2-6, 8-9 and 11 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 2, and 8-9 are “use” claims. The claims are indefinite because they merely recite a use without any active, positive steps delimiting how this use is actually practiced. Although a claim should be interpreted in light of the specification disclosure, it is generally considered improper to read limitations contained in the specification into the claims because it is unclear what limitations should be imparted into the claims.
Claim 3 is an independent claim and it recites the limitation “the soluble CD163” in line 1 while a soluble CD163 is not presented earlier. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites “a reagent” in line 2. It is unclear if “a reagent” is the claimed antibody or any other reagent used for determining fertility.
Claim 11 recites “a method of treating infertility in a patient or a method of increasing establishment of pregnancy in in vitro fertilization” in lines 1-2. There are two methods recited in claim 11. It is unclear which method that “the method” in claim 2 refers to.
Claim 11 recites “the soluble CD163” in line 3. Claim 11 is an independent claim, so there is insufficient antecedent basis for this limitation in the claim because a soluble CD163 is not presented earlier.
Claim 11 recites “a patient” in line 3. It is unclear if a patient in line 3 is the same as a patient in line 1.
Claim 11 recites “an ovum collected from the patient on the same day as the collection of the sample”, “an embryo that has developed from the ovum after fertilization, as having high fertility”, and “an embryo that has developed from the identified ovum after fertilization” in (ii). It appears that “the ovum” and “the identified ovum” refer to an ovum in line 2 of (ii). It is unclear what the difference among “an embryo” in (ii), “an embryo that has developed from the identified ovum after fertilization” and “the identified embryo” in (iii) is because these embryos are all come from the ovum in line 2 of (ii).
Claims 4-6 are also rejected based on their dependency of the defected parent claim.
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 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (including a product of nature) without significantly more. Claim 1 is directed to “a biomarker… comprising soluble CD163.” While the intended uses of this biomarker is recited, the broadest reasonable interpretation of claim 1 is a soluble CD163 which is a biomarker that is naturally present in human body fluid.
Claims 2, 8 and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claims are not directed to a process, or machine, or manufacture, or composition of matter. The claims are directed to the use of CD163 as in claim 2 or the use of an antibody that specifically recognizes CD163 as in claims 8-9 for determining fertility of an ovum, or an embryo that develops from an ovum after fertilization. The claims are not directed to a process, or machine, or manufacture, or composition of matter. The claims may attempt to claim a process of using CD163 or anti-CD163 antibody for determining fertility of an ovum, or an embryo that develops from an ovum after fertilization. However, the claims do not recite any step to point out how to use CD163 or anti-CD163 antibody to achieve the claimed intended use. Thus, the claims are not directed to a process either.
Claim Rejections - 35 USC § 102
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.
Claims 1-2 and 8-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vogel et al. (Preterm delivery predicted by soluble CD163 and CRP in women with symptoms of preterm delivery, an International Journal of Obstetrics and Gynaecology 112, pp. 737–742, 2005).
For claims 1-2, Vogel teaches a soluble form of CD163 (sCD163) has been identified in plasma and can be used to predict a health condition of a subject, e.g., preterm delivery (see Abstract, see page 737 col.2 par.2). While Vogel does not teach the same intended use of the claimed invention, Vogel anticipates the claimed soluble CD163, so the biomarker is capable of performing the claimed intended use.
For claims 8-9, Vogel teaches a use of an antibody that specifically recognizes soluble CD163 for determining fertility (page 738, col.2 par.2 teaching: sCD163 was measured in ELISA by using rabbit anti sCD163 antibody). While Vogel does not teach the same intended use of the claimed invention, Vogel anticipates the claimed antibody (e.g., the antibody that specifically recognizes soluble CD163), so the antibody taught by Vogel is capable of performing the claimed intended use.
Conclusion
Claims 3-6 and 11 are free of the prior art; however they are rejected under 35 U.S.C. 112(a) and 112(b). The prior art of record does not suggest or make obvious a method of detecting soluble CD163 and using CD163 as a biomarker for determining fertility of an ovum, or an embryo that develops from an ovum after fertilization.
The closest prior arts are Diao et al. (Development of a new endometrial immune cell-based score (EI-score) for the prediction of implantation outcomes for patients undergoing IVF/IC, Placenta 99 (2020) 180–188).
Diao discloses an EI-score for predicting implantation success for the patients who received in vitro fertilization, wherein the score includes CD163 + M2-macrophage. However, the score is based on the expression of endometrial immune cell markers in the endometrial tissues, but not based on the presence of soluble CD163 markers in the body fluid (see page 181 section 2.3). Moreover, Diao shows that the expression of CD163 + M2-macrophage was elevated in the implantation failure group. This result is not in line with the claimed invention.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHAU N.B. TRAN whose telephone number is (571)272-3663. The examiner can normally be reached Mon-Fri 8:30-6:30 CT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L Nguyen can be reached at 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHAU N.B. TRAN/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 July 10, 2026
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