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 .
Notice of New Examiner
Please note that the correspondence for this application has changed (see Correspondence section at the end).
Priority
This application was filed 23rd of October 2023 and is a 371 application of PCT/IL22/50389 filed on 13th of April 2022, which claims benefit to the foreign application ISRAEL 282597 filed on 22nd of April 2021.
Election/Restrictions
In Applicant’s response filed on 2nd of June 2026: claims 1-3, 7, 11-13, 15, 21, 24,-25, 38, 41, 49-51 are pending, claims 1, 15, 21, 24, and 49 have been amended, and claims 4-6, 8-10, 14, 16-20, 22-23, 39-40 and 42-48 have been canceled.
Applicants’ election with traverse of Group I, claims 1-3, 7, 11-13, and 38 directed to a genetically modified male bird cell is acknowledged.
The traversal is on the grounds that the cited prior art in the restriction (i.e. Taylor et al.) does disclose the special technical feature of a Z-gametolog (see e.g. Remarks, page 9-11).
The argument regarding the cited prior art is found persuasive; however, in light of the art rejections that follow the special technical feature still lacks novelty, because the examiner was able to provide art which satisfied the limitations of product of group I, thereby demonstrating that a lack of unity exists between the restricted groups (PCT Lack of Unity practice).
Thus, the requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 1-3, 7, 11-13, 15, 21, 24,-25, 38, 41, 49-51 are pending, claims 1, 15, 21, 24, and 49 have been amended, and claims 4-6, 8-10, 14, 16-20, 22-23, 39-40 and 42-48 have been canceled on June 2, 2026.
Claims 24-25, 41 and 50-51 directed to Group II (i.e. synthetic guide RNA) and Group V-VI (i.e. method of making a genetically modified female bird and producing a bird hatchling population biased towards females) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Currently, claims 1-3, 7, 11-13, 15, 21, 38, and 49, are under examination.
Information Disclosure Statement
Applicant is reminded of 37 CFR §1.56, which details Applicant's duty to disclose all information known to be material to patentability.
The information disclosure statements (IDS) submitted on 06/02/2026, 04/20/2026, 04/29/2025, and 10/23/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Applicant is reminded of 37 CFR §1.56, which details Applicant's duty to disclose all information known to be material to patentability. Notably, the disclosure statements filed lists a “Search Reports”. The list of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Claim Rejections - 35 USC § 112
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 1, 3, 7, 11-13, 15, 21, 38, and 49 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 49 recites “confers the ability to produce an essentially female-only hatching population upon breeding” (lines 5-6). The term “essentially” in claim 1 is a relative term which renders the claim indefinite. The closest recitation in the Specification is “The present invention in embodiments thereof provides methods to produce female birds (e.g. chickens) that lay essentially only female offspring” (see e.g. page 12, lines 15-17). Thus, the term “essentially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the parameter of “essentially female-only” in the claim has been rendered indefinite because person of ordinary skill in the art would not be able to ascertain the amount of an “essentially female-only” hatchling population. For compact prosecution, the claimed “essentially female-only” hatching population will read on any amount of an obtained female hatchling population. Appropriate correction is required.
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.
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 1-3, 7, 11-13, 15, 21, 38, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Cinnamon, et al., (WO2020/178822A1, published 2020, cited IDS 10/23/2023; hereinafter as “Cinnamon”), Ayers, et al., (WO2013/155567, published 2013, cited IDS 4/29/2025; hereinafter as “Ayers”), Nam, Kiwoong, and Hans Ellegren., (Genetics 180.2: 1131-1136, 2008, hereinafter as ”Nam”) and Lee et al., (The FASEB Journal, 2019, cited IDS 4/29/2025, hereinafter as “Lee”).
Claim Interpretation: the recitation of “wherein the genetically modified chromosome comprises a chromosome Z-gametolog, when inherited by a female bird offspring, confers the ability to produce an essentially female-only hatchling population upon breeding” is interpreted as product-by-process limitations where the MPEP at 2113 states “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.”
Regarding claims 1-3, 7, 11-13, 15, 38, and 49, Cinnamon discloses a male bird cell (i.e. primordial germ cell (PGC), poultry, chicken) having at least one genetically modified chromosome Z gene having reduced expression and/or activity (see e.g. p. 55-58, claims 1-3, 27, 45 Examples 1-3). Further, Cinnamon discloses wherein said cell is genetically edited using at least one artificially engineered nuclease (i.e. CRISPR-Cas, ZFNs, and TALENS, see e.g. page 15-20 and 55-58). Further, Cinnamon discloses that the bird cell is capable of developing into functional gametes, and is inherited by a female bird offspring, (see e.g. para. 164, Examples 1-3). Further, Cinnamon methods suggest the ability to produce an essentially female-only hatchling population upon breeding (i.e. skewing the ratio)(see e.g. para. 9, claims 1-3, Examples 1-3).
Cinnamon does not explicitly disclose wherein the genetically modified chromosome comprises a chromosome Z-gametolog having reduced expression and/or activity.
However, the prior art of Ayers discloses a method for modifying the sex of a bird (i.e. chicken) by modulating the level of expression and/or activity of endogenous nucleotide sequences that are expressed at a reduced level and discloses wherein the chromosome Z-gametolog genes are W-linked genes such as, zfr, chd1, atp5a, hintz, ubap2, nipbl, hnrnpk, and znf532 (see e.g. p. 2, 4, 6, 50, 54, claims 1-9, Tables 2-3). Additionally, the prior art of Nam discloses that chromosome Z-gametolog genes (i.e. W-linked genes), such as hnrnpk and mier3 have consistently shown female-biased expression indicative of a W-linkage, along with zfr and znf532 genes, which are closely related gene copies identified on the Z chromosome (see e.g. p. 1132-1133, table 1).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have combined the male bird cell, as taught by Cinnamon, to incorporate the genetically modified chromosome Z-gametolog, as taught by Ayers and Nam, with a reasonable expectation of success because one of ordinary skill in the art would know that chromosome Z-gametolog genes with W-linked genes have consistently shown female-biased expression (i.e. genes hnrnpk, mier3, zfr, and znf532)(see e.g. page table 1, respectively and Nam page 1132). Furthermore, an artisan of ordinary skill in the art of (i.e. avian gene expression) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
[AltContent: textbox ([img-media_image1.png]
[img-media_image2.png])]Regarding claims 15 and 21, as stated supra, Cinnamon discloses methods where the cell is genetically edited using a synthetic guide RNA comprising a targeting nucleotide sequence complementary to a target nucleic acid sequence within a bird chromosome Z-gametolog (see e.g. para. 159, p. 55-58, fig. 3)
Cinnamon et al., does not explicitly disclose the synthetic guide RNA comprising a targeting nucleotide sequence complementary to a target nucleic acid sequence within a bird chromosome Z-gametolog that is SEQ ID NO: 1 and SEQ ID NO:2.
However, the prior art of Ayers discloses the targeting sequence of Z chromosome nucleotide sequence as the RNA binding ZNF (i.e. RNA binding zinc finger) corresponding to SEQ ID NO: 1 (see results 3, file us-18-556-761-1.align450.rng, SEQ ID NO: 164, 100% Query match), and SEQ ID NO: 2 (see results 2, file us-18-556-761-2.align450.rng, SEQ ID NO: 164, 100% Query match) (see sequence alignment below)(see e.g. pages 16-27).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the male bird cell with synthetic guide RNA, as taught by Cinnamon, to incorporate the synthetic guide RNA comprising a targeting nucleotide sequence complementary to a target nucleic acid sequence within a bird chromosome Z-gametolog, as taught by Ayers, with a reasonable expectation of success because one of ordinary skill in the art would know the targeting sequence of Z chromosome nucleotide sequence, such as the RNA binding ZNF (i.e. RNA binding zinc finger), would allow for the Z-gametolog W-linked genes (e.g. zfr, mier3, or znf532) to have a continued role in sexual differentiation (as taught by Ayers , see e.g. Figure 8, Examples 2-3). Further, the prior art of Lee discloses that through programmable genome editing methods involving zinc finger nucleases are known to enhance gene targeting, and have been successfully adopted in avian species (see e.g. p. 7-9). Thus, a person of ordinary skill in the art would have done so to limit off target effects. Furthermore, an artisan of ordinary skill in the art of (i.e. avian gene expression) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: Kagami, Hiroshi, et al. (Molecular Reproduction and Development: Incorporating Gamete Research 48.4: 501-510, 1997; hereinafter as “Kagami”), and Nätt, et al., (PLoS One 9.4: e96376, 2014; hereinafter as “Natt”).
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE GONZALES whose telephone number is (571)272-1794. The examiner can normally be reached M-Th: 10AM - 5:00PM (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Josephine Gonzales PhD
Examiner
Art Unit 1638
/JOSEPHINE GONZALES/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
Prosecution Insights