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 .
Claim Interpretation
Claims 1, 2, and 4-10 all state “at least one selected from a follicle-stimulating hormone receptor (FSHR) and a ligand thereof. As the phrase “at least one” prefaces use of the word “and”, prior art reading on the suppression of either FSHR or a ligand thereof will satisfy the claims.
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.
Claim 7 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: the remaining components of the group referred to in the second line of claim 7, stating “the function of the protein is suppressed by at least one type selected from a group including antibodies…” It is unclear to the Examiner if there are other components to said group that can be used to bind to the FSHR and the ligand thereof or if Applicant intends to limit the scope of the claim to only use of FSHR and ligand specific antibodies.
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(s) 1-4, 6, and 8-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chu et al. (Gonadotropin Signaling in Zebrafish Ovary and Testis Development: Insights From Gene Knockout Study, 2015).
Regarding claim 1: Chu discloses that a double knockout of FSHR and luteinizing hormone subunit beta leads to the generation of sterile male zebrafish. (Pg 1750, Results.) Chu further discloses that LH is able to activate FSHR in the absence of FSH and LHR in order to support gonad development, and in particular male double knockout zebrafish (FSHb:LHR) were as fertile as control WT fish, giving definitive genetic evidence that supports LH cross-reacting with FSHR. (Pg 1753, Results) As such, LHb is acting as a ligand of FSHR in a double knockout male zebrafish model, resulting in an infertile animal.
Regarding claims 2 and 4: Chu discloses a double knockout infertile male zebrafish model (LHR:FSHR), satisfying the requirement of introducing a loss-of-function mutation. (Pg 1750, Results)
Regarding claim 3: Chu discloses use of a TALENs system to generate the double mutant knockout zebrafish. (Pg 1753, Discussion)
Regarding claim 6: As Chu discloses the dual knockdown of FSHR and LHR, this satisfies the claim requirement of at least one protein selected from FSHR and the ligand thereof being suppressed.
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Regarding claims 8 and 9: Chu discloses an experiment involving the crossing of WT female zebrafish with the double knockout LHR:FSHR mutant male zebrafish in Figure 9 on page 1751. As can be seen in Figure 9B below, the fertilization rate of the double knockout male has been reduced to zero when compared to a WT male.
As such, this satisfies the requirement of claim 8 of a male marine fish that has been sterilized via suppression of functional expression of FSHR and a ligand thereof and also claim 9 regarding the introduction of said sterile male to an environment wherein a female is present and their mating producing no viable offspring.
Regarding claim 10: Chu discloses the generation of a mutant female zebrafish which has a knockout mutation of the FSHR gene, which resulted in reduced fertility in the female zebrafish. (Pg 1749, Results) This satisfies the requirement of use of at least one selected from FSHR and the ligand thereof.
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.
Claim(s) 5 is rejected under 35 U.S.C. 103 as being unpatentable over Chu et al. (Gonadotropin Signaling in Zebrafish Ovary and Testis Development: Insights From Gene Knockout Study, 2015) in view of Jones et al. (siRNA for gene silencing: a route to drug target discovery, 2004)
The teachings of Chu et al. are discussed above. While Chu does make use of a TALEN system which incorporates mRNA, Chu fails to teach use of siRNA, shRNA, or miRNA specifically.
Regarding claim 5: Jones et al. teaches that one of the main advantages of using siRNA is that it allows for ease in identification of antisense sequences. (Pg 523, Mechanism of RNAi) They are also resistant to nuclease degradation (pg. 524, Mechanisms of RNAi) and specifically are used in knockdown mutations, not knockout (Pg 524, Mechanisms of RNAi).
It would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to make use of an siRNA in the creation of the double knockout zebrafish taught by Chu. One skilled in the art would be motivated to do so based on the teachings of Jones, who states that siRNAs are resistant to nuclease degradation and allow for ease of identification of antisense sequences. In addition, as siRNAs specifically trigger knockdown mutations instead of knockout mutations, one skilled in the art would have been motivated and had a reasonable expectation of success to make use of them in the creation of the zebrafish organism taught by Chu, as they are a double knockdown mutation. As it is known in the art that techniques utilizing knockout mutations are used to target DNA, not RNA, a person skilled in the art would see it necessary to incorporate the teachings of Jones of use of an siRNA to the protocol as taught by Chu as the method of claim 5 is directed to the targeting of mRNA, not DNA. As such, it is required to make use of a knockdown mutation via siRNA, not a knockout mutation.
Claim(s) 7 is rejected under 35 U.S.C. 103 as being unpatentable over Chu et al. (Gonadotropin Signaling in Zebrafish Ovary and Testis Development: Insights From Gene Knockout Study, 2015) in view of Yao et al. (The effect of induced anti-follicle-stimulating hormone autoantibody on serum hormone level and apoptosis in rat testis, 2012)
The teachings of Chu are discussed above. Chu fails to teach use of an antibody in the knockout of FSHR or a ligand thereof.
Regarding claim 7: Yao teaches that in rats with high levels of an anti-FSH antibody, exaggerated apoptosis of spermatogenic cells was seen when compared with wild type rats. (Pg 85, Results) It is known in the art that inhibition of FSH will further result in the inhibition of FSHR, as FSHR is activated via binding to FSH and FSH is also a ligand of FSHR.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Yao of use of an anti-FHS antibody with the generation of a sterile male zebrafish as taught by Chu. One skilled in the art would have had motivation and a reasonable expectation of success at doing so based on the teachings of Yao, who show increased levels of apoptosis in spermatogenic cells, leading to reduced fertility levels. Furthermore, as FSH is the primary activator/ligand of FSHR, use of an anti-FSH antibody would further create an organism with a nonfunctioning FSHR, as is the goal of the claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 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.
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/HANNA MARIE THUESON/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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