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 .
Priority
Applicant’s claim for the benefit of a prior-filed application provisional application 63139031, filed on 1/19/2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) was filed before the mailing date of the non-final first action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claims 33-52 are rejected under 35 U.S.C. 103 as being unpatentable over Baharvand et al (US 2019/0177689 A1), in view of Gittel et al ( Veterinary Research, 2013), Oda et al (Journal of Bioscience and Bioengineering, 2019), and Harkey et al ( Reproduction, 2013), as evidenced by Llivina et al ( Cytotechnology, 2004).
Regarding claims 33-35, Baharvand et al teach a method for isolating oogonial stem cells (i.e. reproductive tissue- derived cells) from human and mouse ovaries. The method involves mincing the ovarian tissues, this reads on step (a). After that, the minced ovarian tissues are enzymatically digested with collagenase IV at a concentration of approximately 800 U/ml. The method of Baharvand et al also involves mechanical agitation while enzymatically digesting the tissue, this reads on steps (b) and (c). After enzymatic digestion, the supernatant from the digested ovarian tissues is collected, filtered through a 40-um nylon mesh, and centrifuged at a speed of 300 g for 5 minutes. Following the centrifugation, the cell pellet is collected and resuspended in a culture medium, this reads on steps (d) and (e). ( See paragraphs [0077]-[0080]).
The method of Baharvand et al does not include steps (f),(g), and (h).
Gittel et al teach methods to isolate mesenchymal stem cells (MSCs) from human
adipose, umbilical cord, and tendon tissues using a combination of enzymatic and mechanical disassociation steps. In particular, the enzymatic digestion method includes the addition of collagenase to the tissue fragments wherein the mixture is incubated with a continuous agitation. Gittel et al also teach explant method for the isolation of the MSCs from the aforementioned tissues. The explant method involves mincing the solid tissues into pieces, placing the minced tissue in culture dishes, and then covering it with standard culture medium to allow cell migration from the solid tissue. ( See left column on page 3). It should be noted that the explant technique utilized by Gittel et al reads on the instant technique recited in steps (f),(g),and (h). Gittel et al do not exactly teach combining enzymatically separated cell isolates with explant-derived cell isolates. Gittel et al also do not suggest using the explant method to harvest single cell suspension from the partially digested tissue. Gittel et al also do not teach isolating cells from reproductive tissues. However, Gittel et al clearly state that the explant method is less invasive, requires less labor, and has less impact on cell viability. ( See 1st column, 5th paragraph, on page 2). On the other hand, Gittel et al also teach that the enzymatic digestion method produces higher yields and require less time in primary cultures. Therefore, an ordinary skill in the art who is informed about the two techniques could easily envision combining the two techniques when isolating cells from solid tissues, such as reproductive tissues, and would be motivated to do so to increase the single cell yields without compromising cell viability that would arise from prolonged enzymatic digestion.
Therefore, claim 33 would have been obvious to one of ordinary skill in the art, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Baharvand et al teach method for isolating oogonial stem cells from human and mouse ovarian tissues using a combination of enzymatic and mechanical disassociation steps, but fail to suggest combining the enzymatic and explant method. Gittel et al utilize both the enzymatic and explant methods to isolate MSCs from solid tissue. According to Gittel et al, cell isolation from solid tissue using the explant technique requires less labor and has a less impact on cell viability, but the enzymatic digestion method produces higher yields and require less time. Therefore, an ordinary skill in the art who had reviewed Baharvand et al could have come across Gittel et al and immediately recognized the benefit of combining the enzymatic digestion method with the explant method to increase the cell yields without impacting cell viability due to extended enzymatic digestion. There would be a reasonable expectation of success, when harvesting cells from solid tissue, to combine both methods to increase the cell yield.
Regarding claims 36-37, following the discussion above, neither Baharvand et al nor Gittel et al teach isolating cells from feline or canine reproductive tissues, wherein the tissues are obtained by neuter procedure.
Harkey et al teach a method for isolating spermatogonial stem cells from the canine testis. Harkey et al utilize an enzymatic method to isolate spermatogonial stem cells from canine testes, wherein the testes tissue are obtained from a neuter procedure. ( See sections “ Canine testis tissues” and “ Isolation and culture of SPG” on page 77).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was filed to combine the teachings of Baharvand , Gittel, and Hakery to isolate cells from canine reproductive tissue that are obtained from neuter procedure. Employing the method of claim 33 as described by the combined teachings of Baharvand and Gittel should yield predictable results, namely isolating single cell suspension from canine testis tissues. In other words, an ordinary skill in the art who had reviewed the teachings of Baharvand and Gittel could have come across Harkey et al and immediately noticed the benefits of employing the method of claim 33 to isolate cells from canine testis tissue collected by neuter procedure as doing so would increase the single cell yields.
Regarding claims 38-42, the method of Baharvand involves digesting the ovarian tissue with collagenase, this reads on claim 38. Baharvand et al’s method also involves enzymatically digesting ovarian tissue with gentle agitation for 10 minutes, this reads on claim 41. ( See [0078]). Baharvand et al do not teach gentle agitation lasting 40 minutes or more. However, it is well recognized in the art that it would have been prima facie obvious for one with ordinary skill in the art to rely on routine experimentation when determining the optimum time for gentle agitation. Because gentle agitation is used to aid in the enzymatic digestion of the tissue, this parameter varies depending on the tissue type. Therefore, an ordinary skill on the art would be able to arrive at the same time frame claimed in instant claims through routine experimentation.
According to the MPEP, “When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges through routine experimentation. See MPEP 2144.05.
Regarding claim 43-45, following the discussion of claim 33 above, the enzymatic digestion methods taught by Baharvand et al and Gittel et al both involve mechanically agitating the tissue suspension in order to enhance enzymatic digestion of the tissue into single cell suspension. However, Baharvand et al and Gittel et al do not specify the type of agitator/rotor utilized for this step.
Oda et al conduct a comparison study to compare the effectiveness of isolating chondrocytes from cartilage tissues using rotation/revolution agitation versus conventional orbital agitation. Oda et al demonstrate that the efficiency of enzymatically digesting cartilage tissue is dependent on the type of agitator. In particular, Oda et al demonstrate that combining enzymatic digestion of cartilage tissue with rotation/revolution agitation is more effective than the conventional orbital agitation method for the isolation of chondrocytes from cartilage tissue. (See abstract). For example, Oda et al demonstrate that the number of isolated cells was approximately 1.2 *107 and 4.3 *106 cells/g of cartilage tissue in the rotation/revolution and conventional orbital agitation groups, respectively. (See Fig.4B). Taken together, it would have been prima facie obvious for one with ordinary skill in the art at the time the invention was filed to rely on routine experimentation when determining the appropriate form of agitation. Because Oda et al clearly demonstrate that the type of agitation could significantly impact the efficiency of isolating cells from solid tissue. Therefore, an ordinary skill in the art who had reviewed the teachings of Oda et al would be motivated to use routine experimentation to determine the most effective type of agitation for the isolation of cells from reproductive tissues.
According to the MPEP, “When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges through routine experimentation. See MPEP 2144.05.
Regarding claim 46-47, the method of Baharvand involves a filtration step to separate single cell suspension from the partially digested tissue fraction, wherein the filtration step comprises of passing cell suspension through a 40 µm cell strainer. (See [0080]).
Regarding claims 49-50, following the discussion of claim 33, the combined teaching of Baharvand and Gittel render obvious combining the enzymatic digestion with explant method to harvest cells from reproductive tissues. The method of Gittel et al involves incubating the solid tissue extracted from umbilical cord for 7 days. Gittel et al do not teach an incubation period that overlaps with the time frame recited in instant claims. However, it is well recognized in the art that it would have been prima facie obvious for one with ordinary skill in the art to rely on routine experimentation when determining the appropriate incubation time for the explant method. An ordinary skill on the art would be able to arrive at the same time frame claimed in instant claims through routine experimentation. According to the MPEP, “When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges through routine experimentation. See MPEP 2144.05.
Regarding claims 48, neither Baharvand nor Gittel teach storing enzymatically isolated cells at 4 C prior the mixing step. However, storing cells at 4C is a common practice in the art that can be used for short-term cell storage, as evidenced by Llivina et al. ( See abstract). Therefore, temporarily storing cells at 4 C is a claim limitation that is well-understood, routine, and conventional step in the relevant art. Consequently, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to incorporate such common practice into the claimed invention.
Regarding claim 51, following the discussion of claim 33, the combined teaching of Baharvand and Gittel render obvious combining the enzymatic digestion with explant method to harvest cells from reproductive tissues. Neither Baharvand et al nor Gittel et al teach the exact cell number produced per gram of tissue as recited in instant claim; however the claimed outcome is presumed to be inherent in the combined teachings of Baharvand et al in view of Gittel et al, as this advantage would flow naturally from following the combined teachings of Baharvand and Gittel. As per he MPEP “( The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.)"
Regarding claim 52, Baharvand et al also teach cryopreserving (i.e. freezing) cells isolated from the ovarian tissues. ( See [0097]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FATIMAH KHALAF MATALKAH whose telephone number is (703)756-5652. The examiner can normally be reached Monday-Friday,7:30 am-4:30 pm EST.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638