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 Status
Amendments to the claims filed 16 Jul 2024 are acknowledged. Claims 1-8 are pending and under consideration.
Claim Rejections - 35 USC § 101
35 U.S.C. § 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 8 is rejected under 35 U.S.C. § 101 because the claimed invention is directed to a natural product without significantly more. The claim recites a medium comprising a TLR7 ligand with pH 7.7 to 7.9. This judicial exception is not integrated into a practical application because uterine and oviduct tubal fluid has a pH within the claimed range (P. Vishwakarma, Fertil Steril, 1962, p. 483 and Table 1) and natural TLR7 ligands include single-stranded RNA from RNA viruses that can infect the female reproductive tract (T. Umehara, et al., PLOS Biol, 2019, cited in IDS filed 08 Apr 2025, p. 12). The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the recitation "for culturing mammalian sperm, inducing acrosome reaction of Y-chromosome-bearing sperm, and obtaining a sperm population rich in X-chromosome-bearing sperm retaining an acrosome" is a statement of intended use that does not differentiate the medium claimed from uterine or oviduct tubal fluid in an RNA virus-infected female mammal. Statements reciting purpose or intended use may impose structural limitations; however, in the instant case the recited intended use does not appear to impart structural limitations on the medium claimed, and therefore, is not given patentable weight. See MPEP § 2111.02.
The Office published the guidance document entitled 2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance), published 16 Dec 2014. Step 2A was revised to include two prongs (Federal Register / Vol. 84, No. 4 / 07 Jan 2019).
Analysis is as follows:
Step 1: The claim is directed to a composition of matter (a medium).
Step 1: Yes.
Step 2A, Prong One: Examiner evaluates whether the claim recites a judicial exception.
The composition of matter (medium comprising a TLR7 ligand with pH 7.7 to 7.9) is directed to a natural product. The claim recites a composition that is not markedly different from uterine or oviduct tubal fluid in an RNA virus-infected female mammal.
Step 2A, Prong One: Yes.
Step 2A, Prong Two: Examiner evaluates whether the claim recites additional elements that integrate the judicial exception into practical application of the exception.
This exception is not integrated into practical application because the claim does not recite additional elements that integrate the judicial exception into practical application. The recitation "for culturing mammalian sperm, inducing acrosome reaction of Y-chromosome-bearing sperm, and obtaining a sperm population rich in X-chromosome-bearing sperm retaining an acrosome" merely links the natural product to a particular technological use, which is not indicative of integrating the natural product into practical application. See MPEP § 2106.05(h).
Step 2A, Prong Two: No.
Step 2B: Examiner evaluates whether the claim recites additional elements that individually or in combination amount to significantly more than the judicial exception (i.e., whether the additional elements provide an inventive concept).
The additional elements recited in the claim do not add an inventive step to add significantly more than link the natural product to a particular technological use when considered alone or in combination.
Step 2B: No.
The markedly different characteristics analysis performed in Step 2A, Prong One is a comparison of the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties. Product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See MPEP § 2106.04(b)(II). If the claim recites a nature-based product limitation that does not exhibit markedly different characteristics, the claim is directed to a product of nature exception, and the claim will require further analysis to determine eligibility based on whether additional elements add significantly more to the exception. In accordance with this analysis, medium comprising a TLR7 ligand with pH 7.7 to 7.9, for example, is eligible when there is a resultant change in characteristics sufficient to show a marked difference from uterine or oviduct tubal fluid in an RNA virus-infected female mammal. It is concluded here that the claimed medium is not markedly different from its naturally occurring counterpart, uterine or oviduct tubal fluid in an RNA virus-infected female mammal, as the claim does not recite structural limitations that distinguish the medium composition from the composition of uterine or oviduct tubal fluid in an RNA virus-infected female mammal.
The Supreme Court has identified several considerations for determining whether a claim with additional elements amounts to significantly more than the judicial exception itself. Limitations that may qualify as significantly more when recited in a claim with a judicial exception include: improvements to another technology or technical field; improvements to the functioning of the computer itself; applying the judicial exception with, or by use of, a particular machine; effecting a transformation or reduction of a particular article to a different state or thing; adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application; or other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
Limitations that were found not to be enough to qualify as significantly more when recited in a claim with a judicial exception include: adding the words ‘apply it’ (or an equivalent) with the judicial exception; mere instructions to implement an abstract idea on a computer; simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception; adding insignificant extra-solution activity to the judicial exception; or generally linking the use of the judicial exception to a particular technological environment or field of use.
In the instant case, the limitations of the claims do not impose limits on the scope of the claim such that the medium comprising a TLR7 ligand with pH 7.7 to 7.9 is markedly different from a naturally occurring product. Accordingly, based on analysis of the claim as a whole, claim 8 does not recite additional elements adding significantly more than the judicial exception. Thus, claim 8 is rejected under 35 U.S.C. § 101 because the claimed invention is not directed to patent eligible subject matter.
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 1-2 and 4-8 are rejected under 35 U.S.C. §103 as being unpatentable over Umehara 2020 (T. Umehara, et al., Nat Protoc, 2020, cited in IDS filed 16 Jul 2024) in view of Zhou (J. Zhou, et al. PLOS One) and as evidenced by Umehara 2019 (T. Umehara, et al., PLOS Biol, 2019, cited in IDS filed 08 Apr 2025).
Regarding claims 1 and 8, Umehara 2020 teaches a method for sorting X chromosome-bearing and Y chromosome-bearing sperm (preparation of mammalian sperm to obtain a sperm population rich in X-chromosome-bearing sperm retaining an acrosome) by incubating (culturing) sperm in modified human tubal fluid (mHTF) medium comprising a TLR7 ligand (Abstract). Incubation of sperm in mHTF medium comprising R848 (resiquimod, a TLR7 ligand) does not affect acrosome status (Umehara 2019 p. 5). Umehara 2020 further teaches that expression of TLR7 is specific to X chromosome-bearing sperm and that activation of TLR7 suppresses sperm motility, thus allowing for separation of X chromosome-bearing and Y chromosome-bearing sperm based on motility (p. 2647). Umehara 2020 further teaches that the protocol is optimized for fresh sperm from C57BL/6 mice or frozen Japanese Black bulls and that further optimizations are required for use in other strains and breeds (p. 2652).
Regarding claim 2, the mHTF medium taught by Umehara 2020 comprises bovine serum albumin (BSA) (p. 2660).
Regarding claim 4, Umehara 2020 teaches incubation (culture) of sperm for 60 min before separating X chromosome-bearing sperm from Y chromosome-bearing sperm (Abstract).
Regarding claim 5, the TLR7 ligand is resiquimod (R848) (Abstract and p. 2647).
Regarding claim 6, Umehara 2020 teaches that X/Y sorted sperm have been used for artificial insemination of numerous mammalian livestock species (non-human mammals) (p. 2646).
Regarding claim 7, Umehara 2020 teaches in vitro fertilization of mouse and bovid embryos (non-human mammals) using X chromosome-bearing enriched sperm (pp. 2655-2657).
Umehara 2020 is silent regarding the pH of mHTF medium for incubating sperm and thus not teach preparation of mammalian sperm in a medium with a pH of 7.7-7.9 as required by claims 1-2 and 4-8.
However, Zhou teaches that pH affects sperm motility and capacitation, a process that includes the acrosome reaction (Abstract and p. 2). Zhou teaches that sperm incubated at pH of 7.2 or 8.2 maintain motility over the course of incubation, where motility decreases in acidic conditions (Results p. 5 and Fig. 1). Zhou further teaches that human sperm incubated at pH of 7.2 or 8.2 have greater viability and penetrative capacity compared to sperm incubated in acidic conditions (Results p. 5 and Fig. 2). Zhou does not explicitly teach incubation of sperm in at a pH of 7.7 to 7.9 to enrich the X chromosome-bearing sperm population. However, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See MPEP § 2144.05.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to improve the base process of culturing sperm in a medium comprising a TLR7 ligand to enrich the X chromosome-bearing sperm population as taught by Umehara 2020 by adjusting the pH of the medium to 7.7 to 7.9 as taught by Zhou to arrive at the claimed invention. One would be motivated to make such a combination as Umehara 2020 teaches that the method requires further optimization and as Zhou teaches that pH increases sperm motility, which would further enhance the motility differences between X chromosome-bearing sperm inhibited by TLR7 activation compared to Y chromosome-bearing sperm unaffected by TLR7 activation. One would be motivated to optimize the pH values taught by Zhou during routine optimization of the method. One would have a reasonable expectation of success in making the improvement as Zhou demonstrates that higher pH enhances sperm motility, viability, and penetrative capacity and teaches that higher pH is a trigger for the acrosome reaction.
Claim 3 is rejected under 35 U.S.C. §103 as being unpatentable over Umehara 2020 (T. Umehara, et al., Nat Protoc, 2020, cited in IDS filed 16 Jul 2024) and Zhou (J. Zhou, et al. PLOS One) as applied to claims 1-2 and 4-8 above and in further view of Umehara 2019 (T. Umehara, et al., PLOS Biol, 2019, cited in IDS filed 08 Apr 2025) and Mukai (C. Mukai and M. Okuno, Biol Reprod, 2004).
Umehara 2020 and Zhou teach a method of preparing sperm by culturing sperm in a medium comprising a TLR7 ligand at pH of 7.7 to 7.9 to induce the acrosome reaction and enrich the X chromosome-bearing population as discussed in the rejection of claims 1-2 and 4-8 under 35 U.S.C. § 103 above.
Umehara 2020 teaches that the basis for enriching X chromosome-bearing sperm by TLR7 activation is suppression ATP production required for motility (pp. 2647 and 2649-2650).
Umehara 2020 and Zhou do not teach incubation in a medium containing neither pyruvic acid nor lactic acid as required by claim 3.
However, Umehara 2019 teaches that the basis for enriching X chromosome-bearing sperm by TLR7 activation is mediated through inhibition of hexokinase, the rate-limiting enzyme in glycolysis, which is required for conversion of glucose to metabolites required for mitochondrial ATP production (p. 11). Furthermore, Mukai teaches that supplying sperm with pyruvate (pyruvic acid) or lactate (lactic acid) are sufficient for high ATP production and high motility in the absence of glucose. Therefore, the glycolysis pathway can be bypassed in sperm when hexokinase is inhibited by TLR7 activation.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to improve the base process of culturing sperm in a medium comprising a TLR7 ligand to enrich the X chromosome-bearing sperm population as taught by Umehara 2020 and Zhou by removing pyruvic acid and lactic acid as taught by Umehara 2019 and Mukai to arrive at the claimed invention. One would be motivated to make such a combination as Umehara 2020 and Umehara 2019 teach that the basis for separation of X chromosome-bearing and Y chromosome-bearing sperm is TLR7 activation in X chromosome-bearing to suppress glycolysis, which is required for conversion of glucose for ATP production required for motility and as Mukai teaches that supplementation of sperm with pyruvic acid and lactic acid bypasses glycolysis. One would have a reasonable expectation of success in making the improvement as Mukai teaches that pyruvate or lactate are sufficient for high ATP production and high motility in the absence of glucose.
Conclusion
No claim is allowed.
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Eric B Wright, PhD
Examiner
Art Unit 1632
/Eric B Wright/Examiner, Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632
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