DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 17 October 2025 has been entered.
Claim 1 has been amended. Claims 11-20 remain withdrawn. Claims 1-5, 7, 9, and 10 are currently pending and under examination.
This application is a continuation of International Patent Application No. PCT/US2020/041858, filed July 13, 2020, which claims priority to U.S. Provisional Application No. 62/873263, filed July 12, 2019.
New/Modified Rejections:
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.
Claims 1-5, 7, 9, and 10 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. The claim(s) contains 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.
Claim 1 newly recites that microinjection is performed at a pressure ranging from “about 50 hPa to about 250 hPa.” The limitation of “about” modifying this range is new matter. The only recitation in the specification regarding this pressure range reads as follows:
The loaded needle was positioned perpendicular to the ovary and guided into the ovarian cortex, where the follicle-OECM mixture was slowly injected at a constant pressure ranging from 50-250 hPa (Specification, p. 29, line 20-22).
As this recitation includes the range of exactly 50-250 hPa, modification by inclusion of the term “about” broadens this range to include amounts below and above 50-250 hPa, which are new matter.
Claims 2-5, 7, 9, and 10 are included in this rejection, as these claims depend from above rejected claim 1, and fail to remedy the noted deficiency.
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 1-5, 7, 9, and 10 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.
With regard to claim 1, step (d) recites in relevant part “exposing the pre-gel solution to physiological conditions to initiate gelation of the pre-gel solution to form a hydrogel” (emphasis added). This limitation is indefinite, because it appears that the terms “hydrogel” and “pre-gel solution” are used interchangeably by Applicant in the specification:
In certain embodiments, the methods disclosed herein include mixing the immature follicle with a hydrogel, where the hydrogel is a pre-gel solution (emphasis added) (p. 13, line 21-23).
Upon isolation, immature follicles (primordial, primary and secondary follicles) are selected and mixed with a 4 mg/ml of ovarian specific ECM hydrogel (pre-gel solution)” (emphasis added) (p. 45, 8.2 Example 2, line 4-6).
As such, it is unclear how the “pre-gel solution” and “hydrogel” as now recited in the claims are differentiated, and if they are intended to be structurally different from each other.
It is noted that Applicant appears to use the term “pre-gel” in the specification when the hydrogel is chilled and kept on ice (see for example, Specification, p. 28, line 5-7). However, no such limitation relating to temperature or conditions is set forth in the claims.
Claim 9 recites the limitation "the decellularized ovarian tissue" in line 2. There is insufficient antecedent basis for this limitation in the claim. No decellularized ovarian tissue is previously recited in the claims.
Further regarding claim 9, this claim is indefinite, because it is unclear if reference to the hydrogel in this claim intends to refer to the newly presented pre-gel solution, or instead to the in vivo gelled hydrogel. Further, it is unclear if an extracellular matrix of the decellularized ovarian tissue is intending to refer to the ovarian-specific extracellular matrix of claim 1, or to a different component.
Claim 10 is indefinite, because it is unclear if reference to the hydrogel in this claim intends to refer to the newly presented pre-gel solution, or instead to the in vivo gelled hydrogel. Further, it is unclear if “one or more ovary-specific component” includes the already present ovary-specific ECM of claim 1, or instead requires one or more additional components.
Claims 2-5 and 7 are included in this rejection, as these claims depend from above rejected claims and fails to remedy the noted deficiencies.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 10 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 10 recites that the hydrogel comprises one or more ovary-specific components. However, claim 1 as amended recites that the hydrogel includes an ovarian specific extracellular matrix, which is an ovary-specific component. As such, claim 10 fails to further limit the subject matter of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1-5, 7, 9, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Brown et al. (IDS; US 2017/0252485, Published 2017).
With regard to claims 1 and 10, Brown et al. teach a method of restoring reproductive health and/or fertility in a subject in need thereof (Abs.; Para. 61; Ex. 5). The method comprising providing an immature follicle; mixing the immature follicle with a hydrogel to form a follicle-hydrogel mixture, and delivering the follicle-hydrogel mixture to the subject, wherein the immature follicle matures in vivo in the ovary (Ex. 5, Para. 61, 211; Fig. 25). The hydrogel, which is mixed with the follicle, comprises one or more ovary-specific components including extracellular matrix proteins (Para. 10), which is an ovarian-specific extracellular matrix. The immature follicle mixed with the hydrogel as taught, is a “pre-gel solution” as defined by Applicant (see Specification, p. 13, line 21-23).
Brown et al. further teach that the ovarian-derived hydrogel is capable of gelation at physiologic conditions, e.g., 37° C, making it ideal for in vivo applications (Para. 9). As the ovarian-derived hydrogel is intended for in vivo applications, and as gelation occurs at physiologic conditions, it would have been obvious to one of ordinary skill in the art to store the created ovarian-derived hydrogel under conditions to prevent gelation and maintain the function of the hydrogel to restore reproductive health or fertility (i.e. maintain viability), until the time of implantation into the subject.
Brown et al. additionally teach that the ovarian-derived hydrogel is injected into the ovary of the subject, where the subject is a mouse (Ex. 5), which is exposing the pre-gel solution to physiological conditions to initiate gelation of the pre-gel solution to form a hydrogel. Brown et al. teach the hydrogel/pre-gel solution as claimed, and injection of the hydrogel into a subject as claimed. As such, injection of the hydrogel/pre-gel solution into the in vivo environment as taught would provide the result of the hydrogel having a storage modulus from about 80 Pa to about 350 Pa after gelation.
As noted, Brown et al. teach that the ovarian-derived hydrogel is injected into the ovary of the subject, where the subject is a mouse (Ex. 5). It is further taught that when utilizing the tissue of mice for the method, microscale tools are utilized (Para. 44, 131, 137). As microscale tools are utilized when working with mice, a microinjection needle would be used for injection into the mouse subject as taught. Further, it would have been obvious to one of ordinary skill in the art to utilize a needle of appropriate scale dependent on the subject to be injected, and also to minimize discomfort and tissue damage in the subject receiving the injection into the ovary. Such determination of needle size, including the use of a microinjection needle, would have been routine for an ordinary artisan in a laboratory or clinical setting. It is noted that while Applicant generally discusses the meaning of the term “about,” no limiting definition is set forth (see Specification, p. 9, line 31 to p. 10, line 7). As such, injection using microtools into the subject mouse ovary at any pressure within the inherent injection pressure range of a microinjection needle is deemed to be encompassed within “about” 50 hPa to “about” 250 hPa.
Brown et al. render obvious the method as claimed, including the components as claimed. As such, the result of increasing the number of follicles capable of improving fertility outcomes would naturally flow from performance of the method as rendered obvious.
With regard to claims 2 and 3, Brown et al. teach that the subject has previously received a chemotherapeutic agent (Ex. 5, Para. 211), which is a cancer treatment, and mimics a subject that has cancer.
With regard to claim 4, Brown et al. teach that the immature follicle is derived from an autologous source (Para. 51), which is isolated from ovarian tissue of the subject.
With regard to claim 5, Brown et al. teach that the immature follicle is isolated by enzymatic dissociation of the ovarian tissue (Para. 43; Fig. 25).
With regard to claim 7, Brown et al. teach that the immature follicle is a primordial follicle (Para. 195, 199), or a secondary follicle (Fig. 25).
With regard to claim 9, Brown et al. teach that the hydrogel comprises an extracellular matrix (ECM) of decellularized ovarian tissue, the ECM present at a concentration including 2, 5, and 10 mg/ml (2. Materials and Methods, 2.1- 2.2; Fig. 16A-C), which are fully encompassed within about 1 mg/ml to about 10 mg/ml.
Response to Arguments
Applicant urges that Brown does not disclose a pre-gel solution as now claimed. Additionally, a skilled artisan would recognize that the newly claimed pressure of about 50 hPa to about 250 hPa is specifically chosen to deliver follicles suspended in a liquid solution through a microinjection needle without damage. Applicant further urges that Brown administers matured oocytes and not immature follicles that mature in vivo within the ovary as claimed. Applicant additionally urges that the claimed method exhibits unexpected therapeutic benefits, as the hydrogels of the current method have a storage modulus of about 80 Pa to about 350 Pa after gelation, which is significantly stiffer than the hydrogels of Brown, yet follicle viability within the ovary is maintained for at least 100 days.
Applicant’s arguments have been fully considered, but have not been found persuasive.
With regard to Applicant’s argument that Brown does not teach a pre-gel solution as now claimed; this limitation is addressed in the new and modified rejections above.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the follicles are suspended in a liquid solution) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). There is no claimed requirement that the pre-gel solution be a liquid. It is further noted that there is no requirement for the temperature of the pre-gel solution in the claims, such as the pre-gel solution is chilled. While Applicant provides examples of what such conditions could be, these conditions, such as temperatures, are not claimed. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Additionally, there is no claimed storage time requirement. Thus, the method may be performed at room temperature, where “storing” is simple the time between mixing the immature follicle with a hydrogel and delivering the follicle-hydrogel mixture to the ovary.
With regard to Applicant’s argument that Brown administers matured oocytes and not immature follicles that mature in vivo within the ovary as claimed; while Brown teaches that matured oocytes can be transplanted, Brown also specifically teaches other embodiments:
“Alternatively, the follicle or biological sample can be placed inside the hydrogel. The follicle can be transplanted together with the hydrogel into a subject for preserving fertility” (Para. 61); and
“The ovarian hydrogel is loaded with follicles and injected into the ovarian cortex of both the chemo-treated and POF mice then mated with male mice to produce a litter” (Example 5, In Vivo Study, Para. 211).
Thus, Brown specifically teaches transplanting immature follicles that are intended to mature in vivo within the ovary.
With regard to Applicant’s argument about unexpected results and the stiffness of the hydrogels; it is noted that while Applicant now claims that the storage modulus of the hydrogel is about 80 Pa to about 350 Pa, there is no claimed requirement that the hydrogels be 4 mg/mL or 8 mg/mL. As such, the noted results are not applicable to the method as currently claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 7, 9, and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10-13 and the disclosure of U.S. Patent No. 11,458,224. Although the claims at issue are not identical, they are not patentably distinct from each other because both encompass a method that provide the result of restoring reproductive health and/or fertility in a subject in need thereof, the claimed methods both comprising: providing an immature follicle; mixing the immature follicle with a hydrogel to form a follicle-hydrogel mixture, and delivering the follicle-hydrogel mixture to the subject, wherein the immature follicle matures in vivo in the ovary (‘224 Disclosure: Ex. 5; Fig. 25; Col. 10, line 55 to Col. 11, line 4). The hydrogel, which is mixed with the follicle, comprises one or more ovary-specific components including extracellular matrix proteins (‘224 Disclosure: Col. 2, line 63 to Col. 3, line 8), which is an ovarian-specific extracellular matrix. The immature follicle mixed with the hydrogel as taught, is a “pre-gel solution” as defined by Applicant (see Specification, p. 13, line 21-23).
The ovarian-derived hydrogel is capable of gelation at physiologic conditions, e.g., 37° C, making it ideal for in vivo applications (‘224 Disclosure: Col. 2, line 44-62). As the ovarian-derived hydrogel is intended for in vivo applications, and as gelation occurs at physiologic conditions, it would have been obvious to one of ordinary skill in the art to store the created ovarian-derived hydrogel under conditions to prevent gelation and maintain the function of the hydrogel to restore reproductive health or fertility (i.e. maintain viability), until the time of implantation into the subject.
The ovarian-derived hydrogel is injected into the ovary of the subject, where the subject is a mouse (‘224 Disclosure: Ex. 5), which is exposing the pre-gel solution to physiological conditions to initiate gelation of the pre-gel solution to form a hydrogel. The ‘244 Disclosure sets forth the hydrogel/pre-gel solution as claimed, and injection of the hydrogel into a subject as claimed. As such, injection of the hydrogel/pre-gel solution into the in vivo environment as taught would provide the result of the hydrogel having a storage modulus from about 80 Pa to about 350 Pa after gelation.
As noted, the ovarian-derived hydrogel is injected into the ovary of the subject, where the subject is a mouse (‘224 Disclosure: Ex. 5). It is further taught that when utilizing the tissue of mice for the method, microscale tools are utilized (‘244 Disclosure: Col. 7, line 26-28; Col. 16, line 39-40, 55-60). As microscale tools are utilized when working with mice, a microinjection needle would be used for injection into a mouse subject as taught. Further, it would have been obvious to one of ordinary skill in the art to utilize a needle of appropriate scale dependent on the subject to be injected, and also to minimize discomfort and tissue damage in the subject receiving the injection into the ovary. Such determination of needle size, including the use of a microinjection needle, would have been routine for an ordinary artisan in a laboratory or clinical setting. It is noted that while Applicant generally discusses the meaning of the term “about,” no limiting definition is set forth (see Specification, p. 9, line 31 to p. 10, line 7). As such, injection using microtools into the subject mouse ovary at any pressure within the inherent injection pressure range of a microinjection needle is deemed to be encompassed within “about” 50 hPa to “about” 250 hPa.
The claims and disclosure of the ‘244 patent together render obvious the method as claimed, including the components as claimed. As such, the result of increasing the number of follicles capable of improving fertility outcomes would naturally flow from performance of the method as rendered obvious. (Instant claims: 1, 10; Cited patent claim 1, 10-13 and noted passages of disclosure).
The subject is in need of the method, including due to having cancer, and has previously received a cancer treatment (Instant claim: 2-3; Cited patent claim 1, 10-13, and Col. 21, Ex. 5). The immature follicle is isolated from ovarian tissue of the subject (Instant claim: 4; Cited Patent claim 1, 10-13, and Col. 21, Ex. 5). The immature follicle is isolated by an enzymatic treatment of the ovarian tissue (Instant claim: 5; Cited patent claim 1, 10-13, and Fig. 25). The immature follicle is a primordial follicle or a secondary follicle (Instant claim: 7; Cited patent claim 1, 10-13, and Col. 18, line 40-40; Fig. 25). The extracellular matrix is present in a concentration between about 1 mg/ml to about 10 mg/ml (Instant claim: 9; Cited patent claim 1).
Response to Arguments
Applicant urges that the claims are not obvious over the cited patent, which corresponds to the Brown reference, for the same reasons set forth regarding the obviousness rejection.
Applicant’s arguments have been fully considered, but have not been found persuasive.
Applicant’s arguments regarding Brown have been addressed above.
Conclusion
No claims are allowable.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653