DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/21/2026 has been entered.
Withdrawn Objections and Rejections
The nonstatutory double patenting rejections of claims 130-133 over the claims of copending Application No. 17/480,402 have been withdrawn, necessitated by amendments filed 09/21/2026, which cancelled the claims.
The nonstatutory double patenting rejections of claims 130-133 over the claims of copending Application No. 16/771,191 have been withdrawn, necessitated by amendments filed 09/21/2026, which cancelled the claims.
The nonstatutory double patenting rejections of claims 130-133 over the claims of U.S. Patent No. 11531026 have been withdrawn, necessitated by amendments filed 09/21/2026, which cancelled the claims.
The rejection of claims 130-133 under 35 U.S.C. 102 has been withdrawn, necessitated by amendments filed 09/21/2026, which cancelled the claims.
Status of Claims
Claims 1, 4, 7, 23, 25, 40-43, 45, 48, 50, 61, 80, 98 and 129, and 134-137 are pending and examined herein.
Claims 2-3, 5-6, 8-22, 24, 26-39, 44, 46-47, 49, 51-60, 62-79, 81-97, 99-128, and 130-133 have been cancelled by the Applicant.
New and Modified Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 4, 7, 23, 25, 40-42, 129, and 134-135 are rejected under 35 U.S.C. 103 as being unpatentable over Funk (WO 2005042721 A2, published 2005-05-12, cited in PTO-892 dated 06/02/2025) in view of Lassalle et al. (“Human zona pellucida recognition associated with removal of sialic acid from human sperm surface”, published 1994, cited in PTO-892 dated 06/02/2025). These are modified rejections, necessitated by amendments filed 09/21/2026.
Funk teaches a method for separating X chromosome-bearing sperm cells and Y chromosome-bearing sperm cells with a sample sperm cell population, comprising: differentiating between sperm cells that have undergone capacitation and sperm cells that have not undergone said capacitation; and separating said sperm cells that have undergone said capacitation and said sperm cells that have not undergone said capacitation; wherein a majority of said sperm cells that have undergone said capacitation comprise one of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells; and wherein a majority of said sperm cells that have not undergone said capacitation comprise the other of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells, as in claim 1 (see, e.g., differentiating sperm cells that have undergone capacitation - Funk, page 3, lines 2-7; separating cells that have undergone capacitation – Funk, page 3, lines 11-15; wherein majority of sperm cells that have undergone capacitation comprise one of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells – Funk, page 3, lines 7-11).
Funk teaches that differentiating between sperm cells is facilitated by Y chromosome-bearing sperm cells undergoing capacitation more quickly than X chromosome-bearing sperm cells, as in claim 4 (see, e.g., Funk, page 5, lines 23-25).
Funk teaches inducing capacitation to produce a capacitation-induced sperm cell subpopulation in which said capacitation is induced in at least a portion of Y chromosome-bearing sperm cells, as in claim 7 (see, e.g., inducing capacitation - page 9, lines 6-12; at least a portion Y chromosome-bearing sperm cells – page 5, lines 23-24). The examiner understands the induction of capacitation to be equivalent to the promotion of capacitation because induce and promote are synonyms according to www.merriam-webster.com/thersarus/induce.
Funk fails to teach differentiating the X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells by employing saccharides as a capacitation indicator and binding a capacitation indicator associator, specifically a lectin, to the capacitation indicator and differentiating the sperm cells that have undergone the acrosome reaction from the sperm cells that have not undergone the acrosome reaction by employing an acrosome reaction indicator that associates with an acrosome reaction indicator associator, as in claims 1, 23, 25, and 40-42. However, in a journal article on change to the human sperm surface, Lassalle rectifies these deficiencies. Lassalle teaches saccharides as a capacitation indicator, as in claims 1 and 23 (see, e.g., page 707, column 1, paragraph 3: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” Emphasis added, and page 710, column 1, paragraph 2: “Capacitation is associated with the decrease in the net surface charge and loss of carbohydrates, including sialic acid”). Lassalle teaches lectins binding to saccharides on sperm, as in claim 25 (see, e.g., page 703, under Abstract). Lassalle discloses lectins are used to assess sperm acrosome reaction, as in claims 40-42 (see, e.g., page 707, column 1, paragraph 3). Lassalle teaches the lectins binding to saccharides on sperm are peanut agglutin and concanavalin A, as in claims 134-135 (see, e.g., page 707, column 1, paragraph 3: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” Emphasis added, and page 710, column 1, paragraph 2: “Capacitation is associated with the decrease in the net surface charge and loss of carbohydrates, including sialic acid”).
Funk teaches inducing capacitation by incubating sperm in TALP (pH 7.4), which increases the external pH from a baseline external pH of at least 0.36 pH, as in claim 129 (see, e.g., p. 10, lines 14-17).
Funk and Lasselle are analogous to the field of the claimed invention because they are both in the field of mammalian fertility. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the lectins of Lassalle to the method of Funk. The artisan would have been motivated to do so because Lasselle discloses that lectins can differentiate capacitated sperm cells from non-capacitated sperm cells and acrosome-reacted sperm cells from non-acrosome-reacted sperm cells while Funk disclosed, “As X- and Y-bearing sperm age, they undergo various process[sic], such as capacitation and the acrosome reaction at different rates” (see, e.g., Funk, page 3, lines 5-7). The combination of these disclosures would render obvious the method of differentiating X- and Y-bearing sperm cells from each other using lectins. An artisan would have had a reasonable expectation of success considering the given disclosures.
Funk does not explicitly state that the baseline external pH is determined and that the TALP buffer is increasing the external pH of the sample, as in claim 129. However, in page 5 of the instant specification, the Applicant discloses that “capacitation-inducing media which may be useful with the instant method can include Tyrode’s albumin lactate pyruvate (TALP) medium/buffer” (see, e.g., page 5, lines 13-14). Also, in the “Example” disclosed in the instant specification, the Applicant discloses that the baseline pH of the ejaculate was determined to be 5.93 (see, e.g., page 29, line 27). The Applicant further recites, “The sperm cell pellet was resuspended in sperm TALP buffer (BGM-1, pH 7.3)” (see, e.g., page 29, line 29). The pH of the buffer in Funk is higher than the pH of the buffer in the instant application example (pH 7.4 vs 7.3). An artisan of ordinary skill would have determined the baseline external pH because this metric is known in the art and determining is a mental process. The increase of pH to induce capacitation is an expected result based on the disclosure of Funk. An artisan would have had a reasonable expectation of success considering the given disclosures.
Claims 43 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Funk (cited above) and Lassalle (cited above), as applied to claims 1, 4, 7, 23, 25, 40-42, 129, and 134-135 above, and further in view of Manandhar (Gaurishankar Manandhar, Kiyotaka Toshimori, "Exposure of Sperm Head Equatorin after Acrosome Reaction and Its Fate after Fertilization in Mice", Biology of Reproduction, Volume 65, Issue 5, 1 November 2001, Pages 1425–1436, cited in PTO-892 dated 06/02/2025).
Funk and Lassalle teach as set forth above, but fail to teach equatorin as the acrosome reaction indicator and an equatorin antibody as the acrosome reaction indicator associator, as in claims 43 and 45. However, Manandhar rectifies this by teaching equatorin as the acrosome reaction indicator, as in claim 43 (see, e.g., page 1431, under “DISCUSSION”: “Equatorin is exposed after acrosome reaction that coincides with the functional maturity of the overlying equatorial plasma membrane to participate in fusion”). Manandhar teaches an antibody for equatorin, as in claim 45 (see, e.g., page 1425, column 2, paragraph 2).
Funk, Lassalle, and Manandhar are considered analogous to the claimed invention because they are in the same field of mammalian fertility. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to use the antibody for the acrosome reaction indicator, equatorin, of Manandhar in the method of Funk and Lassalle. The artisan would have been motivated to do so because “equatorin contained in the posterior acrosome is detectable only after spontaneous or induced acrosome reactions” (see, e.g., Manandhar, page 1425, under “ABSTRACT”). This disclosure of equatorin as an acrosome reaction indicator and the antibody for equatorin would be useful to the artisan when differentiating and separating X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells because Funk also disclosed that, “As X- and Y-bearing sperm age, they undergo various process[sic], such as capacitation and the acrosome reaction at different rates” (see, e.g., Funk, page 3, lines 5-7). An artisan would have had a reasonable expectation of success considering the given disclosures.
Claims 48, 50, 61, 80, and 98 are rejected under 35 U.S.C. 103 as being unpatentable over Funk and Lassalle, as applied to claims 1, 4, 7, 23, 25, 40-42, 129, and 134-135 above, and further in view of Hudson (US 20090208977 A1, published 2009-08-20, cited in PTO-892 dated 06/02/2025). These are modified rejections, necessitated by amendments filed 09/21/2026.
Funk and Lassalle teach as set forth above. Funk and Lassalle also teach the separation of non-viable sperm cells and viable sperm cells, as in claim 98 (see, e.g., Funk, page 3, lines 11-15). Funk and Lassalle also teach the capacitation indicator comprises a saccharide and the capacitation indicator associator comprises a lectin that binds to the saccharide, as in claims 130-131 (see, e.g., page 707, column 1, paragraph 3: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” Emphasis added, and page 703, under Abstract). The examiner understands that dead populations of sperm cells are non-viable and alive populations of sperm cells would be viable. But, Funk and Lassalle fail to teach a method comprising a magnetic first particle associated with said capacitation indicator associator, said first particle separable from said sample sperm cell population by the application of a magnetic force to which said first particle is responsive, as in claim 48. Funk and Lassalle fail to teach applying the force to the sample sperm population, as in claim 50. Funk and Lassalle fail to teach the capacitation indicator associator is conjugated to the particle, as in claim 61. Funk and Lassalle fail to teach a second particle conjugated to an acrosome reaction indicator associator, wherein the particle is separable from the sample sperm cell population, as in claim 80. However, Hudson rectifies these deficiencies in a patent application publication entitled “MATERIALS AND METHODS FOR SPERM SEX SELECTION”. Hudson teaches a method for separating X- and Y-chromosome bearing sperm in a sperm sample comprising contacting the sample with specific binding agents on the surface of magnetic beads (or magnetic first particles) then separating the sperm cells bound to the binging agents from the unbound sperm cells by applying a magnetic force to the sample, as in claims 48, 50, 61, and 80 (see, e.g., Hudson, claims 1, 2, and 6). The examiner understands a binding agent to be equivalent to an associator and binding agents on the surface of magnetic particles to be equivalent to associator-particles.
Funk, Lassalle, and Hudson are analogous to the field of the claimed invention because they are all in the field of fertility. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the associator-particles of Hudson into the methods of Funk and Lassalle. The artisan would have been motivated to do so because a binding agent, such as an antibody specifically binds to an antigen that is specific for an X- or Y- chromosome (see, e.g., Hudson, cover page, under “ABSTRACT”). Lassalle teaches lectins (a binding agent) as capacitation indicator associators as cited above. Furthermore, the use of the magnetic particles coated with a binding agent allows the sperm carrying the X-chromosome to be “easily separated by removing the supernatant from the vessel” (see, e.g., Hudson, page 5, column 2, paragraph [0044]). Regarding the ease of associator-magnetic particle separation, an artisan would have had a reasonable expectation of success considering the given disclosures.
In regards to claim 80, Hudson teaches the use of associator-particles for separating X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells and the use of a second associator immobilized on a substrate (see, e.g., Hudson, claims 6 and 7), but does not explicitly teach the use of two different associator-particles. However, in the instant case the number of different associator-particles and the order that they are used are clearly parameters that a person of ordinary skill in the art would routinely optimize (see MPEP § 2144.05). Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. As noted in In re Aller, 105 USPQ 233 at 235, “More particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation”. Routine optimization is not considered inventive and no evidence has been presented that arriving at the steps of claim 80, i.e. adding a second associator-particle and using simultaneously or stepwise, was anything other than routine, that claim 80 resulting from optimization has any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization would have been obvious at the time of the instant invention. An artisan would have had a reasonable expectation of success considering the given disclosures.
Claims 136-137 are rejected under 35 U.S.C. 103 as being unpatentable over Funk (WO 2005042721 A2, published 2005-05-12, cited in PTO-892 dated 06/02/2025) and Lassalle et al. (“Human zona pellucida recognition associated with removal of sialic acid from human sperm surface”, published 1994, cited in PTO-892 dated 06/02/2025), as applied to claims 1, 4, 7, 23, 25, 40-42, 129, and 134-135, and further in view of D’Cruz (“Fluorescence-labeled fucolectins are superior markers for flow cytometric quantitation of the human sperm acrosome reaction”, published 1996-04). These are new rejections, necessitated by amendments filed 09/21/2026.
Funk and Lassalle teach as set forth above but fail to teach the lectins comprise Pisum sativum agglutinin (PSA) and Anguilla anguilla agglutinin (AAA), as in claims 136-137. However, D’Cruz teaches binding FITC-labeled PSA and AAA lectins to capacitated human sperm for quantitation, as in claims 136-137 (see, e.g., p. 843, under abstract, under “Design”: “The binding of five FITC-labeled lectins (PSA, PNA, AAA, TPA, and UEA-l) to capacitated, calcium ionophore A23187 (Can-treated, or solvent-treated human sperm was quantitated by fluorescence flow cytometry”).
Funk, Lassalle, and D’Cruz are analogous to the field of the claimed invention because they are all in the field of fertility. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to substitute PNA of Funk and Lassalle with PSA and AAA of D’Cruz. An artisan would have been motivated to do so because it would be simple substitution of equivalents due to D’Cruz listing PNA in a list of labeled lectins alongside PSA and AAA. An artisan would have had a reasonable expectation of success based on the given disclosures.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 7, 23, 25, 40-43, 45, 48, 50, 61, 80, 98, and 129 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 7, 21-23, 25, 40-43, 45, 48-51, 61, 80, 98, and 129 of copending Application No. 17/480,402 (referred to as ‘402 hereto).
With respect to claim 1, ‘402 teaches a method for separating X chromosome-bearing sperm cells and Y chromosome-bearing sperm cells within a sample sperm cell population, comprising: differentiating between sperm cells that have undergone capacitation and sperm cells that have not undergone said capacitation by: employing a capacitation indicator which is associated with capacitated sperm cells; and binding a capacitation indicator associator to said capacitation indicator; and separating said sperm cells that have undergone said capacitation and said sperm cells that have not undergone said capacitation; wherein a majority of said sperm cells that have undergone said capacitation comprise one of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells; and wherein a majority of said sperm cells that have not undergone said capacitation comprise the other of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells (see, e.g., claims 1 and 21-22).
With respect to claim 4, ‘402 teaches wherein said differentiating between sperm cells that have undergone said capacitation and sperm cells that have not undergone said capacitation is facilitated by said Y chromosome-bearing sperm cells undergoing said capacitation more quickly than said X chromosome-bearing sperm cells (see, e.g., claim 4 of ‘402).
With respect to claim 7, ‘402 teaches the method further comprising inducing said capacitation to generate a capacitation-induced sperm cell subpopulation in which said capacitation is induced in at least a portion of said Y chromosome-bearing sperm cells (see, e.g., claim 7 of ‘402).
With respect to claim 23, ‘402 teaches wherein said capacitation indicator comprises a saccharide (see, e.g., claim 23 of ‘402).
With respect to claim 25, ‘402 teaches wherein said capacitation indicator associator comprises a lectin which binds to said saccharide (see, e.g., claim 25 of ‘402).
With respect to claim 40, ‘402 teaches a method further comprising differentiating between sperm cells that have undergone the acrosome reaction and sperm cells that have not undergone said acrosome reaction; wherein said sperm cells that have undergone said acrosome reaction comprise acrosome-reacted sperm cells; and wherein said sperm cells that have not undergone said acrosome reaction comprise non- acrosome-reacted sperm cells (see, e.g., claim 40 of ‘402).
With respect to claim 41, ‘402 teaches a method further comprising employing an acrosome reaction indicator which is associated with said acrosome-reacted sperm cells to differentiate said acrosome-reacted sperm cells from said non-acrosome-reacted sperm cells (see, e.g., claim 41 of ‘402).
With respect to claim 42, ‘402 teaches a method furthering comprising associating an acrosome reaction indicator associator with said acrosome reaction indicator to differentiate said acrosome-reacted sperm cells from said non-acrosome-reacted sperm cells (see, e.g., claim 42 of ‘402).
With respect to claim 43, ‘402 teaches a method, wherein said acrosome reaction indicator comprises equatorin (see, e.g., claim 43 of ‘402).
With respect to claim 45, ‘402 teaches a method wherein said acrosome reaction indicator associator comprises an antibody which associates with said equatorin (see, e.g., claim 45 of ‘402).
With respect to claim 48, ‘402 teaches a method comprising a magnetic first particle associated with said capacitation indicator associator, said first particle separable from said sample sperm cell population by the application of a magnetic force to which said first particle is responsive (see, e.g., claims 1, 21-22, and 48-51).
With respect to claim 50, ‘402 teaches a method further comprising applying said force to said sample sperm cell population (see, e.g., claim 50 of ‘402).
With respect to claim 61, ‘402 teaches a method wherein said capacitation indicator associator is conjugated to said first particle to provide a capacitation indicator associator-particle (see, e.g., claim 48 of ‘402).
With respect to claim 80, ‘402 teaches a method further comprising a second particle associated with said acrosome reaction indicator associator, said second particle separable from said sample sperm cell population; wherein said acrosome reaction indicator associator is conjugated to said second particle to provide an acrosome reaction indicator associator-particle (see, e.g., claim 80 of ‘402).
With respect to claim 98, ‘402 teaches a method further comprising: differentiating between non-viable sperm cells and viable sperm cells; and separating said non-viable sperm cells and said viable sperm cells (see, e.g., claim 98 of ‘402).
With respect to claim 129, ‘402 teaches a method of claim 7, further comprising inducing said capacitation by increasing the external pH (pHe) (see, e.g., claim 129 of ‘402).
In regards to claims 129, ‘402 teaches inducing capacitation by increasing the external pH (see, e.g., claim 129 of ‘402), but does not explicitly teach that the baseline external pH is determined and the increase of pH is 0.36 pH units. However, in the instant case the increase of pH used is clearly a parameter that a person of ordinary skill in the art would routinely optimize (see MPEP § 2144.05). Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. As noted in In re Aller, 105 USPQ 233 at 235, “More particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation”. Routine optimization is not considered inventive and no evidence has been presented that arriving at the steps of claim 129, i.e. using a pH increase of 0.36 pH units, was anything other than routine, that the properties of claim 129 resulting from optimization has any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization would have been obvious at the time of the instant invention. Furthermore, an artisan of ordinary skill would have determined the baseline external pH because this metric is known in the art and determining is a mental process. An artisan would have had a reasonable expectation of success considering the given disclosures.
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Claims 1, 4, 7, 23, 25, 40-43, 45, 48, 50, 61, 80, 98, 129, and 134-137 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6, 16, and 25 of copending Application No. 16/771,191 (referred to as ‘191 hereto) in view of Funk (cited above), Lassalle (cited above), Manandhar (cited above), Hudson (cited above), and D’Cruz (cited above).
‘191 teaches a method for separating X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells, as in claims 1 and 48 (see claim 1 of ‘191). ‘191 teaches the sperm cells are capacitated, as in claims 1 and 4 (see claim 5 of ‘191). ‘191 teaches the sperm cells comprise acrosome reacted cells, as in claim 42 (see claim 6 of ‘191). ‘191 teaches increasing the pH environment of sperm cells about 0.36, as in claim 129 (see claim 16 of ‘191). ‘191 teaches a method further comprising a magnetic first particle associated with a capacitation indicator associator, said first particle separable from said sample sperm cell population by the application of a magnetic force to which said first particle is responsive, as in claim 48 (see claim 25 of ‘191).
The deficiencies of ‘191 are rectified by the following disclosures. Funk teaches a method for separating X chromosome-bearing sperm cells and Y chromosome-bearing sperm cells with a sample sperm cell population, comprising: differentiating between sperm cells that have undergone capacitation and sperm cells that have not undergone said capacitation; and separating said sperm cells that have undergone said capacitation and said sperm cells that have not undergone said capacitation; wherein a majority of said sperm cells that have undergone said capacitation comprise one of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells; and wherein a majority of said sperm cells that have not undergone said capacitation comprise the other of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells, as in claim 1 (see, e.g., differentiating sperm cells that have undergone capacitation - Funk, page 3, lines 2-7; separating cells that have undergone capacitation – Funk, page 3, lines 11-15; wherein majority of sperm cells that have undergone capacitation comprise one of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells – Funk, page 3, lines 7-11).
Funk teaches that differentiating between sperm cells is facilitated by Y chromosome-bearing sperm cells undergoing capacitation more quickly than X chromosome-bearing sperm cells, as in claim 4 (see, e.g., Funk, page 5, lines 23-25).
Funk teaches inducing capacitation to produce a capacitation-induced sperm cell subpopulation in which said capacitation is induced in at least a portion of Y chromosome-bearing sperm cells, as in claim 7 (see, e.g., inducing capacitation - page 9, lines 6-12; at least a portion Y chromosome-bearing sperm cells – page 5, lines 23-24). The examiner understands the induction of capacitation to be equivalent to the promotion of capacitation because induce and promote are synonyms according to www.merriam-webster.com/thersarus/induce.
Funk and ‘191 fail to teach differentiating the X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells by employing saccharides as a capacitation indicator and binding a capacitation indicator associator, specifically a lectin, to the capacitation indicator and differentiating the sperm cells that have undergone the acrosome reaction from the sperm cells that have not undergone the acrosome reaction by employing an acrosome reaction indicator that associates with an acrosome reaction indicator associator, as in claims 1, 23, 25, and 40-42. However, in a journal article on change to the human sperm surface, Lassalle rectifies these deficiencies. Lassalle teaches saccharides as a capacitation indicator, as in claims 1 and 23 (see, e.g., page 707, column 1, paragraph 3: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” Emphasis added, and page 710, column 1, paragraph 2: “Capacitation is associated with the decrease in the net surface charge and loss of carbohydrates, including sialic acid”). Lassalle teaches lectins binding to saccharides on sperm, specifically peanut agglutinin and concanavalin A, as in claims 25 and 134-135 (see, e.g., page 703, under Abstract, and page 707, column 1, paragraph 3: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” Emphasis added, and page 710, column 1, paragraph 2: “Capacitation is associated with the decrease in the net surface charge and loss of carbohydrates, including sialic acid”).). Lassalle discloses lectins are used to assess sperm acrosome reaction, as in claims 40-42 (see, e.g., page 707, column 1, paragraph 3).
Funk teaches inducing capacitation by incubating sperm in TALP (pH 7.4), which increases the external pH from a baseline external pH of at least 0.36 pH, as in claim 129 (see, e.g., p. 10, lines 14-17).
‘191, Funk, and Lasselle are analogous to the field of the claimed invention because they are both in the field of mammalian fertility. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the lectins of Lassalle to the method of Funk. The artisan would have been motivated to do so because Lasselle discloses that lectins can differentiate capacitated sperm cells from non-capacitated sperm cells and acrosome-reacted sperm cells from non-acrosome-reacted sperm cells while Funk disclosed, “As X- and Y-bearing sperm age, they undergo various process[sic], such as capacitation and the acrosome reaction at different rates” (see, e.g., Funk, page 3, lines 5-7). The combination of these disclosures would render obvious the method of differentiating X- and Y-bearing sperm cells from each other using lectins. An artisan would have had a reasonable expectation of success considering the given disclosures.
Funk does not explicitly state that the baseline external pH is determined and the TALP buffer is increasing the external pH of the sample, as in claim 129. However, in page 5 of the instant specification, the Applicant discloses that “capacitation-inducing media which may be useful with the instant method can include Tyrode’s albumin lactate pyruvate (TALP) medium/buffer” (see, e.g., page 5, lines 13-14). Also, in the “Example” disclosed in the instant specification, the Applicant discloses that the baseline pH of the ejaculate was determined to be 5.93 (see, e.g., page 29, line 27). The Applicant further recites, “The sperm cell pellet was resuspended in sperm TALP buffer (BGM-1, pH 7.3)” (see, e.g., page 29, line 29). An artisan of ordinary skill would have determined the baseline external pH because this metric is known in the art and determining is a mental process. The pH of the buffer in Funk is higher than the pH of the buffer in the instant application example (pH 7.4 vs 7.3). The increase of pH to induce capacitation is an expected result based on the disclosure of Funk. An artisan would have had a reasonable expectation of success considering the given disclosures.
‘191, Funk, and Lassalle teach as set forth above, but fail to teach equatorin as the acrosome reaction indicator and an equatorin antibody as the acrosome reaction indicator associator, as in claims 43 and 45. However, Manandhar rectifies this by teaching equatorin as the acrosome reaction indicator, as in claim 43 (see, e.g., page 1431, under “DISCUSSION”: “Equatorin is exposed after acrosome reaction that coincides with the functional maturity of the overlying equatorial plasma membrane to participate in fusion”). Manandhar teaches an antibody for equatorin, as in claim 45 (see, e.g., page 1425, column 2, paragraph 2).
‘191, Funk, Lassalle, and Manandhar are considered analogous to the claimed invention because they are in the same field of mammalian fertility. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to use the antibody for the acrosome reaction indicator, equatorin, of Manandhar in the method of Funk and Lassalle. The artisan would have been motivated to do so because “equatorin contained in the posterior acrosome is detectable only after spontaneous or induced acrosome reactions” (see, e.g., Manandhar, page 1425, under “ABSTRACT”). This disclosure of equatorin as an acrosome reaction indicator and the antibody for equatorin would be useful to the artisan when differentiating and separating X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells because Funk also disclosed that, “As X- and Y-bearing sperm age, they undergo various process[sic], such as capacitation and the acrosome reaction at different rates” (see, e.g., Funk, page 3, lines 5-7). An artisan would have had a reasonable expectation of success considering the given disclosures.
‘191, Funk, and Lassalle teach as set forth above. Funk and Lassalle also teach the separation of non-viable sperm cells and viable sperm cells, as in claim 98 (see, e.g., Funk, page 3, lines 11-15). But, Funk and Lassalle fail to teach a method comprising separating sperm cells that have undergone capacitation from cells that have not by employing a magnetic particle associated with the capacitation indicator associator; wherein the magnetic particle is separable from the sample sperm cell population by the application of a magnetic force to which the particle is responsive, as in claim 48. Funk and Lassalle fail to teach applying the force to the sample sperm population, as in claim 50. Funk and Lassalle fail to teach the capacitation indicator associator is conjugated to the particle, as in claim 61. Funk and Lassalle fail to teach a second particle conjugated to an acrosome reaction indicator associator, wherein the particle is separable from the sample sperm cell population, as in claim 80. However, Hudson rectifies these deficiencies in a patent application publication entitled “MATERIALS AND METHODS FOR SPERM SEX SELECTION”. Hudson teaches a method for separating X- and Y-chromosome bearing sperm in a sperm sample comprising contacting the sample with specific binding agents on the surface of magnetic beads then separating the sperm cells bound to the binging agents from the unbound sperm cells by applying a magnetic force to the sample, as in claims 48, 50, 61, and 80 (see, e.g., Hudson, claims 1, 2, and 6). The examiner understands a binding agent to be equivalent to an associator and binding agents on the surface of magnetic particles to be equivalent to associator-particles.
'191, Funk, Lassalle, and Hudson are analogous to the field of the claimed invention because they are all in the field of fertility. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the associator-particles of Hudson into the methods of Funk and Lassalle. The artisan would have been motivated to do so because a binding agent, such as an antibody specifically binds to an antigen that is specific for an X- or Y- chromosome (see, e.g., Hudson, cover page, under “ABSTRACT”). Lassalle teaches lectins (a binding agent) as capacitation indicator associators as cited above. Furthermore, the use of the magnetic particles coated with a binding agent allows the sperm carrying the X-chromosome to be “easily separated by removing the supernatant from the vessel” (see, e.g., Hudson, page 5, column 2, paragraph [0044]).
In regards to claim 80, Hudson teaches the use of associator-particles for separating X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells and the use of a second associator immobilized on a substrate (see, e.g., Hudson, claims 6 and 7), but does not explicitly teach the use of two different associator-particles. However, in the instant case the number of different associator-particles and the order that they are used are clearly parameters that a person of ordinary skill in the art would routinely optimize (see MPEP § 2144.05). Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. As noted in In re Aller, 105 USPQ 233 at 235, “More particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation”. Routine optimization is not considered inventive and no evidence has been presented that arriving at the steps of claim 80, i.e. adding a second associator-particle and using simultaneously or stepwise, was anything other than routine, that claim 80 resulting from optimization has any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization would have been obvious at the time of the instant invention. An artisan would have had a reasonable expectation of success considering the given disclosures.
With regards to claims 136-137, ‘191, Funk, Lassalle, and Hudson teach as set forth above but fail to teach the lectins comprise Pisum sativum agglutinin (PSA) and Anguilla anguilla agglutinin (AAA), as in claims 136-137. However, D’Cruz teaches binding FITC-labeled PSA and AAA lectins to capacitated human sperm for quantitation, as in claims 136-137 (see, e.g., p. 843, under abstract, under “Design”: “The binding of five FITC-labeled lectins (PSA, PNA, AAA, TPA, and UEA-l) to capacitated, calcium ionophore A23187 (Can-treated, or solvent-treated human sperm was quantitated by fluorescence flow cytometry”).
‘191, Funk, Lassalle, Hudson, and D’Cruz are analogous to the field of the claimed invention because they are all in the field of fertility. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to substitute PNA of Funk and Lassalle with PSA and AAA of D’Cruz. An artisan would have been motivated to do so because it would be simple substitution of equivalents due to D’Cruz listing PNA in a list of labeled lectins alongside PSA and AAA. An artisan would have had a reasonable expectation of success based on the given disclosures.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 4, 7, 23, 25, 40-43, 45, 48, 50, 61, 80, 98, 129, and 134-137 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 7 of U.S. Patent No. 11531026 (referred to as ‘026 hereto) in view of Funk (cited above), Lassalle (cited above), Manandhar (cited above), Hudson (cited above), and D’Cruz.
‘026 teaches a method for separating sperm cells with particles based on subpopulation indicators, as in claims 1 and 48 (see claim 1 of ‘026). ‘026 teaches the sperm cells are capacitated, as in claims 1 and 4 (see claim 7 of ‘026). ‘026 teaches a method further comprising a magnetic first particle with said capacitation indicator associator, said first particle separable from said sample sperm cell population by the application of a magnetic force to which said first particle is responsive, as in claim 48 (see claim 4 of ‘026).
The deficiencies of ‘026 are rectified by the following disclosures. Funk teaches a method for separating X chromosome-bearing sperm cells and Y chromosome-bearing sperm cells with a sample sperm cell population, comprising: differentiating between sperm cells that have undergone capacitation and sperm cells that have not undergone said capacitation; and separating said sperm cells that have undergone said capacitation and said sperm cells that have not undergone said capacitation; wherein a majority of said sperm cells that have undergone said capacitation comprise one of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells; and wherein a majority of said sperm cells that have not undergone said capacitation comprise the other of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells, as in claim 1 (see, e.g., differentiating sperm cells that have undergone capacitation - Funk, page 3, lines 2-7; separating cells that have undergone capacitation – Funk, page 3, lines 11-15; wherein majority of sperm cells that have undergone capacitation comprise one of said X chromosome-bearing sperm cells or said Y chromosome-bearing sperm cells – Funk, page 3, lines 7-11).
Funk teaches that differentiating between sperm cells is facilitated by Y chromosome-bearing sperm cells undergoing capacitation more quickly than X chromosome-bearing sperm cells, as in claim 4 (see, e.g., Funk, page 5, lines 23-25).
Funk teaches inducing capacitation to produce a capacitation-induced sperm cell subpopulation in which said capacitation is induced in at least a portion of Y chromosome-bearing sperm cells, as in claim 7 (see, e.g., inducing capacitation - page 9, lines 6-12; at least a portion Y chromosome-bearing sperm cells – page 5, lines 23-24). The examiner understands the induction of capacitation to be equivalent to the promotion of capacitation because induce and promote are synonyms according to www.merriam-webster.com/thersarus/induce.
Funk and ‘026 fail to teach differentiating the X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells by employing saccharides as a capacitation indicator and binding a capacitation indicator associator, specifically a lectin, to the capacitation indicator and differentiating the sperm cells that have undergone the acrosome reaction from the sperm cells that have not undergone the acrosome reaction by employing an acrosome reaction indicator that associates with an acrosome reaction indicator associator, as in claims 1, 23, 25, 40-42, and 134-135. However, in a journal article on change to the human sperm surface, Lassalle rectifies these deficiencies. Lassalle teaches saccharides as a capacitation indicator, as in claims 1 and 23 (see, e.g., page 707, column 1, paragraph 3: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” Emphasis added, and page 710, column 1, paragraph 2: “Capacitation is associated with the decrease in the net surface charge and loss of carbohydrates, including sialic acid”). Lassalle teaches lectins binding to saccharides on sperm, specifically lectins comprising peanut agglutinin and concanavalin A, as in claims 25 and 134-135 (see, e.g., page 703, under Abstract, and page 707, column 1, paragraph 3: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” Emphasis added, and page 710, column 1, paragraph 2: “Capacitation is associated with the decrease in the net surface charge and loss of carbohydrates, including sialic acid”).). Lassalle discloses lectins are used to assess sperm acrosome reaction, as in claims 40-42 (see, e.g., page 707, column 1, paragraph 3).
Funk teaches inducing capacitation by incubating sperm in TALP (pH 7.4), which increases the external pH from a baseline external pH of at least 0.36 pH, as in claim 129 (see, e.g., p. 10, lines 14-17).
‘026, Funk, and Lasselle are analogous to the field of the claimed invention because they are both in the field of mammalian fertility. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the lectins of Lassalle to the method of Funk. The artisan would have been motivated to do so because Lasselle discloses that lectins can differentiate capacitated sperm cells from non-capacitated sperm cells and acrosome-reacted sperm cells from non-acrosome-reacted sperm cells while Funk disclosed, “As X- and Y-bearing sperm age, they undergo various process[sic], such as capacitation and the acrosome reaction at different rates” (see, e.g., Funk, page 3, lines 5-7). The combination of these disclosures would render obvious the method of differentiating X- and Y-bearing sperm cells from each other using lectins. An artisan would have had a reasonable expectation of success considering the given disclosures.
Funk does not explicitly state that the baseline external pH is determined and that the TALP buffer is increasing the external pH of the sample, as in claim 129. However, in page 5 of the instant specification, the Applicant discloses that “capacitation-inducing media which may be useful with the instant method can include Tyrode’s albumin lactate pyruvate (TALP) medium/buffer” (see, e.g., page 5, lines 13-14). Also, in the “Example” disclosed in the instant specification, the Applicant discloses that the baseline pH of the ejaculate was determined to be 5.93 (see, e.g., page 29, line 27). The Applicant further recites, “The sperm cell pellet was resuspended in sperm TALP buffer (BGM-1, pH 7.3)” (see, e.g., page 29, line 29). The pH of the buffer in Funk is higher than the pH of the buffer in the instant application example (pH 7.4 vs 7.3). An artisan of ordinary skill would have determined the baseline external pH because this metric is known in the art and determining is a mental process. The increase of pH to induce capacitation is an expected result based on the disclosure of Funk. An artisan would have had a reasonable expectation of success considering the given disclosures.
‘026, Funk, and Lassalle teach as set forth above, but fail to teach equatorin as the acrosome reaction indicator and an equatorin antibody as the acrosome reaction indicator associator, as in claims 43 and 45. However, Manandhar rectifies this by teaching equatorin as the acrosome reaction indicator, as in claim 43 (see, e.g., page 1431, under “DISCUSSION”: “Equatorin is exposed after acrosome reaction that coincides with the functional maturity of the overlying equatorial plasma membrane to participate in fusion”). Manandhar teaches an antibody for equatorin, as in claim 45 (see, e.g., page 1425, column 2, paragraph 2).
‘026, Funk, Lassalle, and Manandhar are considered analogous to the claimed invention because they are in the same field of mammalian fertility. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to use the antibody for the acrosome reaction indicator, equatorin, of Manandhar in the method of Funk and Lassalle. The artisan would have been motivated to do so because “equatorin contained in the posterior acrosome is detectable only after spontaneous or induced acrosome reactions” (see, e.g., Manandhar, page 1425, under “ABSTRACT”). This disclosure of equatorin as an acrosome reaction indicator and the antibody for equatorin would be useful to the artisan when differentiating and separating X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells because Funk also disclosed that, “As X- and Y-bearing sperm age, they undergo various process[sic], such as capacitation and the acrosome reaction at different rates” (see, e.g., Funk, page 3, lines 5-7). An artisan would have had a reasonable expectation of success considering the given disclosures.
‘026, Funk, and Lassalle teach as set forth above. Funk and Lassalle also teach the separation of non-viable sperm cells and viable sperm cells, as in claim 98 (see, e.g., Funk, page 3, lines 11-15). Funk and Lassalle also teach the capacitation indicator comprises a saccharide and the capacitation indicator associator comprises a lectin that binds to the saccharide, as in claims 130-131 (see, e.g., page 707, column 1, paragraph 3: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” Emphasis added, and page 703, under Abstract). The examiner understands that dead populations of sperm cells are non-viable and alive populations of sperm cells would be viable. But, Funk and Lassalle fail to teach a method comprising separating sperm cells that have undergone capacitation from cells that have not by employing a magnetic particle associated with the capacitation indicator associator; wherein the magnetic particle is separable from the sample sperm cell population by the application of a magnetic force to which the particle is responsive, as in claim 48. Funk and Lassalle fail to teach applying the force to the sample sperm population, as in claim 50. Funk and Lassalle fail to teach the capacitation indicator associator is conjugated to the particle, as in claim 61. Funk and Lassalle fail to teach a second particle conjugated to an acrosome reaction indicator associator, wherein the particle is separable from the sample sperm cell population, as in claim 80. However, Hudson rectifies these deficiencies in a patent application publication entitled “MATERIALS AND METHODS FOR SPERM SEX SELECTION”. Hudson teaches a method for separating X- and Y-chromosome bearing sperm in a sperm sample comprising contacting the sample with specific binding agents on the surface of magnetic beads then separating the sperm cells bound to the binging agents from the unbound sperm cells by applying a magnetic force to the sample, as in claims 48, 50, 61, and 80 (see, e.g., Hudson, claims 1, 2, and 6). The examiner understands a binding agent to be equivalent to an associator and binding agents on the surface of magnetic particles to be equivalent to associator-particles.
Funk, Lassalle, and Hudson are analogous to the field of the claimed invention because they are all in the field of fertility. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the associator-particles of Hudson into the methods of Funk and Lassalle. The artisan would have been motivated to do so because a binding agent, such as an antibody specifically binds to an antigen that is specific for an X- or Y- chromosome (see, e.g., Hudson, cover page, under “ABSTRACT”). Lassalle teaches lectins (a binding agent) as capacitation indicator associators as cited above. Furthermore, the use of the magnetic particles coated with a binding agent allows the sperm carrying the X-chromosome to be “easily separated by removing the supernatant from the vessel” (see, e.g., Hudson, page 5, column 2, paragraph [0044]).
In regards to claim 80, Hudson teaches the use of associator-particles for separating X chromosome-bearing sperm cells from Y chromosome-bearing sperm cells and the use of a second associator immobilized on a substrate (see, e.g., Hudson, claims 6 and 7), but does not explicitly teach the use of two different associator-particles. However, in the instant case the number of different associator-particles and the order that they are used are clearly parameters that a person of ordinary skill in the art would routinely optimize (see MPEP § 2144.05). Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. As noted in In re Aller, 105 USPQ 233 at 235, “More particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation”. Routine optimization is not considered inventive and no evidence has been presented that arriving at the steps of claim 80, i.e. adding a second associator-particle and using simultaneously or stepwise, was anything other than routine, that claim 80 resulting from optimization has any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization would have been obvious at the time of the instant invention. An artisan would have had a reasonable expectation of success considering the given disclosures.
‘026, Funk, Lassalle, Manandhar, Hudson, and D’Cruz are analogous to the field of the claimed invention because they are all in the field of fertility. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to substitute PNA of Funk and Lassalle with PSA and AAA of D’Cruz. An artisan would have been motivated to do so because it would be simple substitution of equivalents due to D’Cruz listing PNA in a list of labeled lectins alongside PSA and AAA. An artisan would have had a reasonable expectation of success based on the given disclosures.
Response to Arguments
The applicant arguments filed 09/21/2026 have been considered but have not been found to be persuasive.
35 U.S.C. 103 Rejections
The applicant begins arguments on p. 9 of the applicant’s response filed 09/21/2026. The applicant argues that the claimed “capacitation indicator” is not taught by Lassalle (cited above). The applicant argues that page 707, column 1, paragraph 3 of Lassalle: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” does not teach saccharide as the capacitation indicator. However, the applicant ignores the other cited teaching on page 710, column 1, paragraph 2 of Lassalle: “Capacitation is associated with the decrease in the net surface charge and loss of carbohydrates, including sialic acid”. The two quoted teachings of Lassalle clearly teach saccharides as capacitation indicators. Lassalle teaches that PNA and Con A, lectins which bind saccharides, bind capacitated spermatozoa more often than untreated (non-capacitated spermatozoa) and continues by reciting that capacitation is associated with the loss of carbohydrates, specifically sialic acid. Therefore, an artisan of ordinary skill in the art would understand that saccharides are a capacitation indicator. Furthermore, lectins associate with saccharides and are, therefore, capacitation indicator associators.
The applicant continues arguments on p. 10 by stating that the examiner has construed lectins as analogous to both “capacitation indicator associator” and “acrosome reaction indicator associator”. The applicant claims that the examiner’s rejection constitutes “impermissible double-mapping of Lasalle’s [sic] lectin”. However, the disclosure of Lassalle includes teachings of lectins as both “capacitation indicator associator” and “acrosome reaction indicator associator”. The examiner maintains that the rejection is correct. Page 707, column 1, paragraph 3 of Lassalle recites, “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)”, emphasis added. The teaching of Lassalle establishes that the multiple lectins disclosed are used as both “capacitation indicator associators” and “acrosome reaction indicator associators”. It is clear that lectins being used to assess acrosome reaction is equivalent to saying that saccharides are “acrosome reaction indicators”.
The applicant continues arguments by turning to the 35 U.S.C. 103 rejection of claim 45 starting on p. 12. The applicant state’s that the examiner’s inconsistent mapping of the elements of claims 42 and 45 fail to meet the initial burden of proof for rejecting claim 45 on the grounds of 35 U.S.C. 103. While the references taught all of the elements of claims 42 and 45, the examiner has modified the rejections to increase clarity. See 35 U.S.C. 103 rejections above.
The applicant continues arguments by turning to the 35 U.S.C. 103 rejection of claim 48 starting on p. 13. The applicant states that Funk (cited above) teaches away from combining with Lassalle and Hudson. While the applicant is correct that Funk recites, “This method of producing sex skewed semen sample is of great benefit over current methods as no physical or mechanical sorting of sperm is required” (see, p. 5, line 32 to p. 6, line 2). However, the applicant neglects Funk’s disclosure that “When it is desired to separate distinct X and Y rich fractions, various methods may be used, including separation based on differential sugar affinities expressed by capacitated, acrosome reacted spermatozoa and non-capacitated sperm, Sephadex™ and glass wool filtering, or Optiprep™ and other centrifugation gradients to separate live and dead populations” (see, p. 3, lines 11-15). Funk expresses that their invention is compatible with the separation of distinct X and Y rich fractions, including by saccharide expression by capacitated- and acrosome-reacted sperm. It is clear that the cumulative disclosure of Funk does not teach away from separation.
The applicant continues arguments by turning to the rejection of dependent claims 4, 7, 23, 25, 40-43, 45, 48, 50, 61, 80, 98, 129, and 130-133 on p. 14. The applicant states that because independent claim 1 is both novel and nonobvious in view of the above arguments, the dependent claims are also novel and nonobvious. However, the arguments regarding independent claim 1 have not been found persuasive. Therefore, the dependent claims will remained rejected on the grounds of 35 U.S.C. 103.
Double Patenting Rejection Arguments
On p. 15 of the applicant’s response, the applicant begins arguments regarding the double patenting rejection of claims 1, 4, 7, 23, 25, 40-43, 45, 48, 50, 61, 80, 98, and 129-133 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 7 of U.S. Patent No. 11531026 (referred to as ‘026 hereto) in view of Funk (cited above), Lassalle (cited above), Manandhar (cited above), and Hudson (cited above). The applicant argues that ‘026 does not teach magnetically separating Y chromosome-bearing sperm cells, as in claim 48. However, ‘026 teaches a method for separating sperm cells with particles based on subpopulation indicators (see claim 1 of ‘026). ‘026 teaches the sperm cells are capacitated (see claim 7 of ‘026). ‘026 teaches magnetically separating the Y chromosome-bearing sperm cells (see claim 4 of ‘026). In summary, ‘026 inherently teaches magnetically separating capacitated sperm cells from sperm cells that have not undergone capacitation because, as Funk teaches, Y chromosome-bearing sperm cells undergo capacitation more quickly than X chromosome-bearing sperm cells (see, e.g., Funk, p. 5, lines 23-25). The applicant continues arguments by stating that Lassalle does not teach the claimed (i) "capacitation indicator," (ii) "capacitation indicator associator," (iii) "acrosome reaction indicator," and (iv) "acrosome reaction indicator associator". The applicant argues that page 707, column 1, paragraph 3 of Lassalle: “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)” does not teach saccharide as the capacitation indicator. However, the applicant ignores the other teaching on page 710, column 1, paragraph 2 of Lassalle: “Capacitation is associated with the decrease in the net surface charge and loss of carbohydrates, including sialic acid”. The two quoted teachings of Lassalle clearly teach saccharides as capacitation indicators. Lassalle teaches that PNA and Con A, lectins which bind saccharides, bind capacitated spermatozoa more often than untreated (non-capacitated spermatozoa) and continues by reciting that capacitation is associated with the loss of carbohydrates, specifically sialic acid. Therefore, an artisan of ordinary skill in the art would understand that saccharides are a capacitation indicator. Furthermore, lectins associate with saccharides and are, therefore, capacitation indicator associators. Regarding acrosome reaction indicators and acrosome reaction indicator associators, the applicant claims that the examiner’s rejection constitutes “impermissible double-mapping of Lasalle’s [sic] lectin”. However, the disclosure of Lassalle includes teachings of lectins as both “capacitation indicator associator” and “acrosome reaction indicator associator”. The examiner maintains that the rejection is correct. Page 707, column 1, paragraph 3 of Lassalle recites, “Preliminary studies in which incubation was for 24 h at 4°C showed that percentages of acrosome-reacted spermatozoa assessed by PNA-FITC or Con A—FITC, two lectins used to assess sperm acrosome reaction (Mortimer et al, 1987; Holden et al, 1990), were higher ( < 0.05) for capacited [sic] (39.3%) than for untreated spermatozoa (15.1%)”, emphasis added. The teaching of Lassalle establishes that the multiple lectins disclosed are used as both “capacitation indicator associators” and “acrosome reaction indicator associators”. Lectins being used to assess acrosome reaction is equivalent to saccharides are “acrosome reaction indicators”. Therefore, the arguments submitted by the applicant have not been found persuasive.
Conclusion
No claims are allowed.
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/MICHAEL CAMERON SVEIVEN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
