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 .
Status of Claims
Amendment to claims filed on 07/13/2022 is acknowledged. Claims 1-8 are currently pending and under examination.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
1. Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
Regarding claims 1 and 8, the Specification filed 02/14/2025 does not provide an adequate written description of the claimed invention, particularly regarding the breadth of the recited “CD46-binding ligand” in claims 1 and 8. The claims as currently construed encompass any substance capable of binding to CD46, including peptides, proteins, synthetic ligands, or derivatives thereof, regardless of structure or mechanism. However, the specification only describes and exemplifies anti-CD46 antibodies, specifically monoclonal antibodies such as clone M177 (Examples 1, 15-16), as functional agents for CD46 binding and cell separation. There are no working examples, sequence data, or structural guidance for any non-antibody ligand that binds CD46.
Claims 2-7 depend from claim 1 but do not rectify these deficiencies and are also rejected.
Therefore, the claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
2. Claims 1-8 are also rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement.
Regarding claims 1 and 8, the Specification filed 02/14/2025 fails to enable the full scope of the claimed invention without undue experimentation. While the Specification provides sufficient guidance and working examples for the antibody embodiments including identification of specific clones (M177), reagents, concentrations, and separation protocols, it does not teach how to make or use non-antibody CD46-binding ligands within the claimed scope. The disclosure merely lists general categories of possible ligands and high-level synthesis methods (proteomic or recombinant approaches) (paragraph 0031) without identifying any actual ligand sequences, binding affinities, or assay conditions necessary to determine whether such ligands would function equivalently to antibodies for CD-46 based separation. Developing and validating such ligands would require substantial, iterative experimentation including screening for binding specificity, conjugation to carriers, and optimization of separation conditions, which constitutes undue experimentation for one of ordinary skill in the art.
Claims 2-7 depend from claim 1 but do not rectify these deficiencies and are also rejected.
Therefore, the claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, and 5-7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 recites that the sperm sample free of CD46 presenting cells “containing substantially only sperm cells with undamaged intact heads.” The phrase “substantially only” introduces ambiguity as it is unclear whether “free of CD46-presenting cells” as recited in claim 1 and “substantially only” describe equivalent or distinct purity levels. The specification and claims lack objective criteria or measurement methods that define what quantitative or qualitative threshold constitutes being “substantially only” sperm cells with undamaged intact heads. Therefore, the metes and bounds of the claim are unclear rendering the scope of the claim unascertainable.
Claim 5 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
In the current instance, the Markush grouping of claim 5 is improper and rejected as indefinite because the recitation of “selected from the group comprising” makes the claim unclear in regard to what other alternatives are intended to be encompassed by the claim (MPEP 2173.05(h)).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or change the wording from “comprising” to “consisting” in order to meet Markush grouping requirement of a closed group of alternatives.
Claims 6 and 7 recite “such as” in their recitations. The phrase "such as" renders these claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 8 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ohashi et al. (Journal of Andrology, 1994, 15(1):78-82).
Regarding claim 8 Ohashi teaches a method of separating sperm populations by providing an anti-CD46 monoclonal antibody (clone MH61; see Kawamoto et al.) bound to immunobeads that are magnet recoverable; contacting a human semen sample with antibody-coated beads so that CD46-presenting sperm (acrosome reacted/damaged head sperm) bind to the carrier; and removing the bead-bound (CD46-presenting) cells by retaining the beads with a magnet and thereby obtaining an unbound fraction enriched for CD46-negative sperm with intact, non-reacted heads (Abstract, Methods). In addition, Ohashi teaches the use of washed semen samples and centrifugation to remove seminal plasma before incubation with antibody-coated beads (Methods).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Edwards et al. (WO2017120173, cited on pg. 1 of IDS filed on 07/18/2022) and Silva et al. (cited on pg. 2 of IDS filed on 07/18/2022), in view of Ohashi et al. (cited above) and further in view of Hancock et al. (Journal of Immunological Methods, 1984, 66(1):149-159).
Ohashi, as discussed above, teaches many of the limitations in claims 1-8 of the instant application including a method of separating CD-46 antibody-bound sperm cells from CD-46 free sperm cells through the binding of immunobeads that are magnet recoverable, and the use of washed semen samples and centrifugation to remove seminal plasma before incubation with antibody-coated beads. However, the primary focus in Ohashi is the separation of CD-46 acrosome reacted sperm and retaining the CD-46 bound reacted sperm sample for studies on further acrosome viability and not on the separated sample of CD-46 free sperm cell supernatant. In addition, Ohashi is silent in regards to the limitations taught in claim 6 of the instant application regarding the use of a vessel such as a well, well plate, beaker, capillary, or test tube as a carrier to separate anti-CD46 antibody coated sperm. Edwards et al. and Hancock et al. address these deficiencies.
Edwards teaches a method for improving quality of semen by removal of unhealthy sperm from semen samples by providing an insoluble carrier carrying at least one ligand that binds to an indicator of impaired sperm membrane integrity and/or impaired sperm motility; contacting the semen sample and the insoluble carrier to provide a bound sperm cell population and an unbound sperm cell population; and separating the bound sperm cell population from the unbound sperm population (Background; claim 1). While Edwards is silent on the use of CD-46 as the ligand of choice for separation of unhealthy sperm from the healthy sample, Silva et al. teach that CD46 can be used to discriminate intact and deteriorated/reacted acrosomes using unfixed sperm or in permeabilized sperm (Fig 2.). Silva provides further support of Ohashi’s motivation to use CD46 as the ligand of choice to separate deteriorated sperm from healthy sperm.
While the above sources address the limitations of claims 1-5, and 7-8, they are silent in regards to the limitations in claim 6 of using a carrier that is coated or immobilized on the inner surface of a vessel, such as well, well plate, beaker, capillary or test tube.
Hancock addresses this deficiency by teaching antibody “panning” techniques, in which antibodies are coated on the inner surface of wells on plastic plates (Abstract), are a routine and effective alternative to bead-based immunoseparation for detecting or depleting sperm bearing specific antigens. In their method, antibody-coated plastic surfaces capture antigen-expressing sperm, which remain adhered to the vessel wall, while unbound sperm are removed by washing (Abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Edwards and Silva with that of Ohashi to separate unhealthy/damaged sperm from healthy sperm using CD46 as the ligand of choice to bind unhealthy sperm cells and removing the CD46 bound cells to obtain a sperm sample that is undamaged and free of CD46 presenting cells. One would be motivated to do so to increase the fertility of semen for various purposes including artificial insemination as taught by Edwards. Furthermore, it would also have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the magnetic beads method taught by Ohashi for the antibody-coated vessel format taught by Hancock to achieve the same functional result of binding and removing CD-46 expressing sperm while also recovering the unbound fraction of intact sperm. One would be motivated to do so as the substitution would have been a predictable use of prior art technique to obtain an equivalent separation outcome and that the “panning” technique taught by Hancock offers a simpler and scalable alternative to bead-based separation that can also be used in cases of dilute cell suspensions and for sperm samples with low motility (Abstract). Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
No claim is allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS GEORGE whose telephone number is (571)270-0340. The examiner can normally be reached M-F 8:30am - 5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel E Kolker can be reached at (571) 272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DENNIS GEORGE/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644
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