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 .
Applicant’s response filed 9/19/2025 has been received and entered into the case. Claims 1, 35, 37, 39, 41, 46, 48-52, 54-59 are pending. Claims 1 and 37 are withdrawn. Claims 35, 39, 41, 46, 48-52, 54-59 have been considered on the merits herein. All arguments and amendments have been considered.
The following rejections are withdrawn in light of applicant claim amendments; Claims 56-59 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, Claim(s) 35, 39, 41, 48, 50, 51 rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Rozeboom et al. (US6849394, IDS), Claim(s) 35, 41, 50, 51 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Riffo et al. (Int. J. Androl., vol. 15, 1992, p. 229-237), Claim(s) 35, 41, 50, 51 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kotdawala et al. (J. assist. Reprod. Genet., 2012, vol 29, p. 1447-1453), Claim(s) 39, 48 rejected under 35 U.S.C. 103 as being unpatentable over each of Riffo et al. (Int. J. Androl., vol. 15, 1992, p. 229-237) and Kotdawala et al. (J. assist. Reprod. Genet., 2012, vol 29, p. 1447-1453) as applied to claims 35, 41, 50, 51 above, and further in view of Rozeboom et al. (US6849394, IDS).
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 35, 39, 41, 46, 48-52, 54-59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rozeboom et al. (US6849394, IDS) in view of Andrews et al. (Biology of Reproduction, vol. 51, p. 1238-1247, IDS) and Que et al. (US20140134665).
For examination purposes, a reference which teaches adding exogenous zinc ions to a sperm sample at a concentration of about 1mM to about 3mM is taken to necessarily be decreasing premature capacitation of sperm sample.
A "‘whereby/thereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d. The method step of adding exogenous zinc ions to a sperm sample, and the “thereby decreasing premature capacitation of sperm” is only an intended result of the addition to the sperm sample 1614, 1620 (Fed. Cir. 2003)) as well as a function of the zinc.
The method of Rozeboom is drawn to the same method as claimed, i.e. Rozeboom teaches adding exogenous zinc to a mammalian sperm sample, including bovines, porcine and humans (abstract, col. 1, col. 2, lines 1-17, 25-55, col. 4, lines 50-60, Ex. col. 6, lines 8-16, Ex. 5).
Thus, it is the Examiners position that these results are inherent to the addition of zinc step taught by Rozeboom. One would necessarily expect to achieve the same results when practicing the method of Rozeboom, which is the same as applicants claimed method.
MPEP 2112 Requirements of Rejection Based on Inherency; Burden of Proof [R-08.2012]
The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 and 103. “The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.5.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983).
lll. A REJECTION UNDER 35 U.S.C. 102/103 CAN BE MADE WHEN THE PRIOR
ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS
SILENT AS TO AN INHERENT CHARACTERISTIC
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103, expressed as a 102/103 rejection. “There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C.103 and for anticipation under 35. U.S.C. 102.” In re Best, 562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA 1977). This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. Therefore, a 35 U.S.C. 102/103 rejection is appropriate for these types of claims as well as for composition claims.
Regarding claim 35, Rozeboom teaches adding exogenous zinc to a mammalian sperm sample, including bovines, porcine and humans (abstract, col. 1, col. 2, lines 1-17, 25-55, col. 4, lines 50-60, Ex. col. 6, lines 8-16, Ex. 5).
Regarding claims 41, the adding of exogenous zinc to a sperm sample extends or enhances the viability of the sample when stored (abstract, col. 1, col. 2, lines 1-17, 25-55, col. 4, lines 50-60, Ex. col. 6, lines 8-16, Ex. 5). The reference teaches the addition zinc to a semen extender for storing sperm (col. 2, lines 25-55). The addition of zinc to a semen extender is taken to meet the limitation of claim 41. The claim is interpreted in light of applicant’s specification, which discloses that
“(0074) In certain embodiments, these methods of improving sperm or semen fertility comprise preventing or inhibiting premature capacitation while the sperm or semen is transported or stored.
III. Sperm Extender Compositions and Use Thereof
[0075] Provided herein are compositions for inhibiting capacitation in a sperm sample. The compositions comprise at least about 0.5 M to about 5 M of exogenous zinc ions. For example, the composition may comprise about 1 M to about 3 M of exogenous zinc ions. In various embodiments, the exogenous zinc ions can be provided in the form of a salt (i.e., zinc chloride, ZnCl.sub.2). Other forms of zinc include ZnCO.sub.3, Zn.sub.3(PO.sub.4).sub.2, zinc acetate, zinc citrate, and ZnSO.sub.4.
[0077] In various embodiments, a sperm sample comprising a zinc composition described herein is provided. In other embodiments, a semen medium or extender is provided comprising any zinc composition described herein. In some embodiments, zinc may be added to any commercially available semen extender. The commercially available semen extender may comprise a SPERMVITAL product from Sperm Vital. Preferably, the semen medium or extender has the capability of preventing premature capacitation of spermatozoa in the sample.”
As per MPEP 2111.01, During patent examination, the pending claims must be “given their broadest reasonable interpretation consistent with the specification.” The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the “broadest reasonable interpretation” standard:
The Patent and Trademark Office (“PTO”) determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction “in light of the specification as it would be interpreted by one of ordinary skill in the art.” In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must “conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description.” 37 CFR 1.75(d)(1).
Regarding claim 39, 48, the zinc is added to a semen extender and is taught to be a zinc salt, specifically including ZnCl2 or zinc sulfate, and to be present in amounts ranging from 0.1 mg/L to about 300 mg/L, yet optimal concentrations can be determined for given medium (col. 4, lines 54-60). Regarding the concentration of zinc, take 300 mg/L of zinc chloride, for example (0.3 mg/ml x1000/136.28 (MW of ZnCl2)= 2.2mM), additionally, Ex. 5, teaches concentrations of ZnCl in amounts of 0.05 g/L to 1 g/L and zinc sulfate 0.1-0.5 g/L (col. 9, lines 25-60, Table 6) which fall within applicants claimed about 1mM to about 3mM. Therefore, the reference teaches concentrations falling within and overlapping with applicants claimed ranges of about 1M to about 3M. See MPEP2144.05.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.").
Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%); In re Waite, 168 F.2d 104, 108, 77 USPQ 586, 590 (CCPA 1948); In re Scherl, 156 F.2d 72, 74-75, 70 USPQ 204, 205-206 (CCPA 1946) (prior art showed an angle in a groove of up to 90° and an applicant claimed an angle of no less than 120°); In re Swenson, 132 F.2d 1020, 1022, 56 USPQ 372, 374 (CCPA 1942); In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941); In re Becket, 88 F.2d 684 (CCPA 1937) ("Where the component elements of alloys are the same, and where they approach so closely the same range of quantities as is here the case, it seems that there ought to be some noticeable difference in the qualities of the respective alloys."); In re Dreyfus, 73 F.2d 931, 934, 24 USPQ 52, 55 (CCPA 1934); In re Lilienfeld, 67 F.2d 920, 924, 20 USPQ 53, 57 (CCPA 1933)(the prior art teaching an alkali cellulose containing minimal amounts of water, found by the Examiner to be in the 5-8% range, the claims sought to be patented were to an alkali cellulose with varying higher ranges of water (e.g., "not substantially less than 13%," "not substantially below 17%," and "between about 13[%] and 20%"); K-Swiss Inc. v. Glide N Lock GmbH, 567 Fed. App'x 906 (Fed. Cir. 2014)(reversing the Board's decision, in an appeal of an inter partes reexamination proceeding, that certain claims were not prima facie obvious due to non-overlapping ranges); Gentiluomo v. Brunswick Bowling and Billiards Corp., 36 Fed. App'x 433 (Fed. Cir. 2002)(non-precedential)(disagreeing with argument that overlapping ranges were required to find a claim prima facie obvious); In re Brandt, 886 F.3d 1171, 1177, 126 USPQ2d 1079, 1082 (Fed. Cir. 2018)(the court found a prima facie case of obviousness had been made in a predictable art wherein the claimed range of "less than 6 pounds per cubic feet" and the prior art range of "between 6 lbs./ft3 and 25 lbs./ft3" were so mathematically close that the difference between the claimed ranges was virtually negligible absent any showing of unexpected results or criticality.
Regarding claims 50 and 51, the sperm sample is a fresh sperm sample to which the zinc ions are added (ex. 5).
Rozeboom does not teach identifying infertile, subfertile or fertile sperm according to claim 35.
Andrews teaches that zinc stabilizes cell membranes, DNA and stabilizes sperm during storage and ejaculation. Zinc removal from sperm prepares sperm for fertilization/capacitation (abstract). Andrews teaches that changes that are associated with capacitation include an increase in respiration, change in motility, cholesterol removal, destabilization of sperm membranes and the removal of Zn (Intro. 1st parag.). Andrews teaches that the art demonstrates that Zn (ZnCl2) is an inhibitor of capacitation (intro, 2nd col). Andrews seek to determine the correlation between Zn and sperm capacitation. The reference teaches labeling sperm with a zinc probe, i.e., Zn2+ specific fluorochrome (N-(6-methoxy-8-quinolyl)-p-toluene-sulfonaminide (TSQ)) and propidium iodide and identifying zinc content of sperm before and after capacitation with flow cytometry (abstract, p. 1239, 1st parag., p. 1239, 2nd col., Flow cytometry and the salt-stored section). Andrews also determine if sperm capacitation could be inhibited by the addition of zinc acetate and image analysis was used to locate TSQ fluorescence on a subcellular level (p. 1239, 2nd full parag.). Andrews find that capacitated sperm which are zinc depleted are capable of penetrating the zona pellucida, thus, fertile sperm according to applicants’ definition of fertile or fertility (p. 6, lines 18-22) , and those which are non-capacitated having high zinc content cannot penetrate the zona pellucida, thus infertile sperm (p. 1245, Discussion section, 1st and 2nd parag.).
Regarding claims 35, 54-55, Andrews teaches analyzing sperm to which zinc was added using flow cytometry (p. 1239, Flow cyt. Section -p. 1242) and that fertile/capacitated sperm zinc signatures were further identified using image-based analysis microscopy, and demonstrate that those which were capacitated/fertile show zinc presence/localization in the head/acrosomal region and tail corresponding to applicant’s zinc signature 1 (p. 1241, Effect of zinc-p. 1242, Table 2, BSA1 and BSA2).
Regarding claims 58 and 59, Andrews teaches sperm cells identified on the basis of forward angle light scatter, 90° light scatter and live/dead status using flow cytometry, thus comprising gating (p.1239, Flow cytometry meas. Section).
Andrews also teach the addition of zinc to sperm to determine the effect of sperm capacitation and find that zinc inhibits capacitation and the sperm’s ability to penetrate the zona pellucida (p. 1241 and p. 1243, Effect of added zinc section, Fig. 4).
Additionally, Que teaches a method of detecting cellular zinc concentration including mammalian sperm (from bovine, human or porcine (0007) and correlating the concentration to a cellular phenomenon including to evaluate sperm quality for fertility; wherein the detecting comprises labeling sperm with a zinc-responsive probe and using image-based flow cytometry and microscopy type analysis (abstract, 0006, 0007, 0011, 0023, 0025-0037, 0053, 0078-0080, 0085, 0090, 0093, see examples).
Thus, before the effective filing date of the claimed invention, it would have been obvious to identify fertile, infertile or subfertile sperm by labeling with a zinc probe, identifying the presence or localization of zinc associated with the sperm and comparing the zinc presence to sperm of a reference pattern associated with capacitation using flow cytometry or microscopy methods to determine fertility in view of the teachings of Andrews and Que who teach that sperm can be labeled with a zinc probe to determine sperm quality for fertility and for identifying zinc content of sperm before and after capacitation. Andrews find that capacitated sperm which are zinc depleted are capable of penetrating the zona pellucida, thus, fertile sperm and those which are non-capacitated having high zinc content cannot penetrate the zona pellucida, thus infertile sperm. Therefore, one of ordinary skill in the art would have recognized that applying the methods of Andrews and Que would have yielded predictable results and one would have had a reasonable expectation of successfully determining whether or not the sperm are fertile.
Claim(s) 35, 39, 41, 46, 48-52, 54-59 is/are rejected under 35 U.S.C. 103 as being unpatentable over each of Riffo et al. (Int. J. Androl., vol. 15, 1992, p. 229-237) and Kotdawala et al. (J. assist. Reprod. Genet., 2012, vol 29, p. 1447-1453) in view of Rozeboom et al. (US6849394, IDS) and further in view of Andrews et al. (Biology of Reproduction, vol. 51, p. 1238-1247, IDS) and Que et al. (US20140134665).
Riffo teaches adding exogenous zinc to a human sperm. The zinc is added at a concentration of 1mM and Riffo find that when added at this amount, the number of sperm which undergo the acrosome reaction is decreased and Fig. 4 demonstrates that pre-incubation with 1mM of zinc inhibits the human sperm acrosome reaction and/or capacitation (which is reversible and occurs in a dose-dependent fashion) (summary, p. 230, 2nd and 3rd full parag., p. 231, Effect of zinc section, Results, dose-response effects section, p. 232, 1st full para., Fig. 2, p. 233, Effect of zinc removal section, Fig. 4, p. 235, whole page).
Regarding claim 41, Riffo teaches “storing” for 2-6 hours.
Regarding claims 50-52, the sperm sample is a fresh sperm sample to which the zinc ions are added (p. 230 M&M section-p. 231).
Kotdawala teaches adding exogenous zinc to a sperm sample and cryopreserving/storing. The reference teaches adding 1mM (1000 µM) of zinc sulfate to sperm before cryopreservation (p. 1448, Cryopreserv and thawing section, elucidation of optimium zinc concentration section) and find that zinc supplementation reduces mitochondrial damage, prevents loss of motility, and sperm post-thaw had higher percentages of sperm which were able to undergo capacitation and the acrosome reaction. Kotdawala suggests that the higher capacitation numbers may be due to higher numbers of sperm surviving the freeze-thaw process, wherein the zinc may help in preventing freeze-thaw destabilization of the plasma membrane, thus retaining the acrosomal content (p. 1451, 2nd col, 2nd and 3rd parag.). Thus, the addition of zinc is interpreted as decreasing premature capacitation because the ability of the frozen-thawed sperm to undergo capacitation and the acrosome reactions in vitro was significantly higher in semen sample cryopreserved with zinc (abstract) and the zinc supplementation retained acrosomal contents and prevented plasma membrane destabilization (p. 1451, 2nd col, 2nd and 3rd parag.).
Regarding claims 50-52, the sperm sample is a fresh sperm sample to which the zinc ions are added before cryopreservation (p. 1448, M&M section, semen analysis and cryopreserve. sections).
While each of the references teach the addition of zinc sulfate, the references do not teach ZnCl2 according to claims 39, 46, 48, 49.
Rozeboom teaches adding exogenous zinc to a mammalian sperm sample to extend or enhance the viability of the sample when stored and taken to necessarily be decreasing premature capacitation of sperm sample (abstract, col. 1, col. 2, lines 1-17, 25-55, col. 4, lines 50-60, Ex. col. 6, lines 8-16, Ex. 5). The reference teaches the addition zinc to a semen extender for storing sperm (col. 2, lines 25-55). Regarding claim 39, 48, the zinc is added to a semen extender and is taught to be a zinc salt, specifically including ZnCl2 or zinc sulfate (col. 4, lines 50-57).
Therefore, it would have been obvious to substitute zinc chloride for the zinc sulfate of Riffo and Kotdawala in view of Rozeboom and because the substitution of one known zinc salt for another would have yielded predictable results to one of ordinary skill in the art.
The references do not teach identifying infertile, subfertile or fertile sperm according to claim 35.
Andrews teaches that zinc stabilizes cell membranes, DNA and stabilizes sperm during storage and ejaculation. Zinc removal from sperm prepares sperm for fertilization/capacitation (abstract). Andrews teaches that changes that are associated with capacitation include an increase in respiration, change in motility, cholesterol removal, destabilization of sperm membranes and the removal of Zn (Intro. 1st parag.). Andrews teaches that the art demonstrates that Zn (ZnCl2) is an inhibitor of capacitation (intro, 2nd col). Andrews seek to determine the correlation between Zn and sperm capacitation. The reference teaches labeling sperm with a zinc probe, i.e., Zn2+ specific fluorochrome (N-(6-methoxy-8-quinolyl)-p-toluene-sulfonaminide (TSQ)) and propidium iodide and identifying zinc content of sperm before and after capacitation with flow cytometry (abstract, p. 1239, 1st parag., p. 1239, 2nd col., Flow cytometry and the salt-stored section). Andrews also determine if sperm capacitation could be inhibited by the addition of zinc acetate and image analysis was used to locate TSQ fluorescence on a subcellular level (p. 1239, 2nd full parag.). Andrews find that capacitated sperm which are zinc depleted are capable of penetrating the zona pellucida, thus, fertile sperm according to applicants’ definition of fertile or fertility (p. 6, lines 18-22) , and those which are non-capacitated having high zinc content cannot penetrate the zona pellucida, thus infertile sperm (p. 1245, Discussion section, 1st and 2nd parag.).
Regarding claims 35, 54-55, Andrews teaches analyzing sperm to which zinc was added using flow cytometry (p. 1239, Flow cyt. Section -p. 1242) and that fertile/capacitated sperm zinc signatures were further identified using image-based analysis microscopy, and demonstrate that those which were capacitated/fertile show zinc presence/localization in the head/acrosomal region and tail corresponding to applicant’s zinc signature 1 (p. 1241, Effect of zinc-p. 1242, Table 2, BSA1 and BSA2).
Regarding claims 58 and 59, Andrews teaches sperm cells identified on the basis of forward angle light scatter, 90° light scatter and live/dead status using flow cytometry, thus comprising gating (p.1239, Flow cytometry meas. Section).
Andrews also teach the addition of zinc to sperm to determine the effect of sperm capacitation and find that zinc inhibits capacitation and the sperm’s ability to penetrate the zona pellucida (p. 1241 and p. 1243, Effect of added zinc section, Fig. 4).
Additionally, Que teaches a method of detecting cellular zinc concentration including mammalian sperm (from bovine, human or porcine (0007) and correlating the concentration to a cellular phenomenon including to evaluate sperm quality for fertility; wherein the detecting comprises labeling sperm with a zinc-responsive probe and using image-based flow cytometry and microscopy type analysis (abstract, 0006, 0007, 0011, 0023, 0025-0037, 0053, 0078-0080, 0085, 0090, 0093, see examples).
Thus, before the effective filing date of the claimed invention, it would have been obvious to identify fertile, infertile or subfertile sperm by labeling with a zinc probe, identifying the presence or localization of zinc associated with the sperm and comparing the zinc presence to sperm of a reference pattern associated with capacitation to determine fertility in view of the teachings of Andrews and Que who teach that sperm can be labeled with a zinc probe using flow cytometry and microscopy methods to determine sperm quality for fertility and for identifying zinc content of sperm before and after capacitation. Andrews find that capacitated sperm which are zinc depleted are capable of penetrating the zona pellucida, thus, fertile sperm and those which are non-capacitated having high zinc content cannot penetrate the zona pellucida, thus infertile sperm. Therefore, one of ordinary skill in the art would have recognized that applying the methods of Andrews and Que would have yielded predictable results and one would have had a reasonable expectation of successfully determining whether or not the sperm are fertile.
Response to Arguments
Applicant's arguments filed 9/19/2025 have been fully considered but they are not persuasive.
Regarding the 103 rejections relying upon the Andrews reference, Applicants first argue that Rozeboom, Riffo, Kotdawala and Que do not teach identifying fertile or infertile sperm.
Each of Rozeboom, Riffo, and Kotdawala are relied upon for teaching adding exogenous zinc ions to a sperm sample.
Regarding Andrews, applicants argue that the reference is directed to the role of zinc in hamster sperm capacitation not porcine, bovine or human sperm and teaches lower amounts of zinc. Applicant additionally argue that Andrews destabilization methods differ between species.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The Andrews reference is relied upon herein for teaching that mammalian sperm require the capacity to fertilize an egg through capacitation, during which many changes to sperm cells are seen including the removal of zinc from sperm. In mammals, zinc is present in seminal fluid and sperm and is responsible for maintaining sperm in a quiescent state and stabilizing sperm membranes. The reference teaches that in hamster, mouse and human sperm, zinc can inhibit sperm motility and capacitation. Additionally, the reference teaches adding a zinc probe to sperm and identifying the presence and/or localization of zinc to determine if the sperm is fertile or infertile characterized by the localization of zinc in the sperm head (acrosome) and tail according to applicants claimed zinc signature 1. It should be noted that Andrews uses the salt-stored zona pellucida penetration assay to evaluate sperm capacitation in vitro which is used in hamster, rabbit and human and in the hamster and human (both species in which the block to polyspermy is at the level of the zona pellucida) salt storage destroys the ability of eggs to block polyspermy to the sperm can reach the perivitelline spaces and they retain the ability to discriminate between capacitated and non-capacitated sperm (p. 1239, Salt-stored zona pellucida section). Applicants’ arguments directed to hamster vs human, bovine or porcine is not persuasive because the methods used would apply to mammals including humans.
Applicants argue that Que does not teach comparing zinc patterns in sperm cells to determine sperm fertility. Que is relied upon for teaching detecting and quantifying changes in zinc using a zinc probe using flow cytometry and microscopy type image analysis.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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/TIFFANY M GOUGH/ Examiner, Art Unit 1651
/MELENIE L GORDON/ Supervisory Patent Examiner, Art Unit 1651