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 .
Status of the Claims
The preliminary amendment filed 12/22/2022 is acknowledged. Claim 1 is amended, claims 2-30 are canceled and claims 31-49 are new. No restriction requirement is being imposed in this case. Claims 1 and 31-49 are pending and under examination.
Effective Filing Date
Applicant’s claims for the benefit of a prior-filed application under 35 U.S.C. 365(c) and foreign priority are acknowledged. Under the AIA , the effective filing date of a claimed invention is the earlier of:
The actual filing date of the application;
OR
The filing date to which the application is entitled to a right of foreign priority or domestic benefit as to such claimed invention.
Based on the information given by Applicant and an inspection of the prior application, the examiner has concluded that the subject matter defined in the instant claims is supported by the disclosure in PCT/DK2021/050218, filed 06/30/2021.
Note that with regard to claiming foreign priority, the foreign priority date is the effective filing date of the claimed invention IF
the foreign application supports the claimed invention under 112(a), AND
the applicant has perfected the right of priority by providing:
a certified copy of the priority application, and
a translation of the priority application (if not in English).
In the instant case, the certified copy of the foreign priority application is in English and supports the claimed invention under 112(a), therefore, the effective filing date of the instant application is 07/03/2020.
Drawings
The drawings are objected to because Figure 8, which is spread over three pages, is labeled “Fig. 8, continues” (1st two pages) and “Fig. 8, continued” (last page) instead of 8A-8B, 8C, 8D-8E as is done with the other figures. See 37 C.F.R. § 1.84(U)(1), which states that partial views of a drawing which are intended to form one complete view, whether contained on one or several sheets, must be identified by the same number followed by a capital letter.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 1 and 42 objected to because of the following informalities. In claim 1, “inhibin B” is written in lower case, while in claim 42, it is capitalized. For the sake of consistency, the term should be written the same way throughout the claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 37 and 42-49 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.
(i) Claims 37 and 45 recite a RANKL inhibitor that binds RANKL at the same epitope as denosumab or osteoprotegerin (OPG). Denosumab is an antibody that binds RANKL at a linear epitope consisting of residues 233-241 of RANKL. Osteoprotegerin, on the other hand, is not an antibody, but rather, it is a protein that binds to RANKL at the N-terminal cysteine rich domains to inhibit bone loss. The recitation in the claims of the term, “epitope”, which is generally understood as the portion of a protein or antigen to which an antibody binds, is confusing. In the context of claims 37 and 45, epitope is interpreted as meaning “portion”.
(ii) Claim 42 recites administering a RANKL antagonist/inhibitor to the subject “if said subject has a level of AMH of” followed by a list of four bulleted biomarker endpoints. The last two endpoints recite Inhibin B and are silent with respect to AMH, which leads to confusion because lines 2-3 of the claim appear to require treating the subject if a certain level of AMH is present. Further, the claim encompasses an embodiment in which treatment is not administered; namely, in the case that none of the four biomarker endpoints are met. This leads to confusion about what is being protected by the patent grant because this embodiment does not encompass any active steps delimiting the process of treatment. The claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant (see MPEP 2171).
Claims 43-49 are hereby included in this rejection because they depend upon an indefinite claim without resolving the indefiniteness.
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.
Claims 1 and 31-49 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more. Independent claim 1 recites a method for determining a likely effect of a treatment to improve male fertility comprising determining anti-Müllerian hormone (AMH) or Inhibin B level(s) in a biological sample from a male subject, comparing said determined AMH or Inhibin B level(s) to a corresponding reference level; and determining that said subject will either likely benefit from treatment with a RANKL antagonist/inhibitor if said level(s) is equal to or higher than said reference level or likely not benefit from treatment with a RANKL antagonist/inhibitor if said level is lower than said reference level, wherein if said subject is considered likely to benefit from treatment with an of RANKL antagonist/inhibitor, administering to said subject a RANKL antagonist/inhibitor. Independent claim 42 is drawn to a method of treating male infertility in a subject in need thereof, comprising administering a RANKL antagonist/inhibitor to said subject if said subject has an AMH level above 30 pmol/l in blood serum or above 5 pmol/l in seminal fluid; at least 50 IU/ml Inhibin B in blood serum; or at least 20 IU/ml Inhibin B in seminal fluid. Thus, the claims are drawn to the statutory category of a process. See Step 1 of the Guidelines.
The first step in determining whether a claim recites patent eligible subject matter is to consider whether the claims recite an abstract idea, law of nature or a natural phenomenon (see Prong One of Step 2A in the Guidelines). As noted above, independent claim 1 recites determining AMH or Inhibin B level(s) in a biological sample, comparing said determined AMH or Inhibin B level(s) to a reference; and determining, based upon said comparison, that the subject will benefit from treatment with a RANKL antagonist/inhibitor if the levels are the same or higher than reference or will not benefit if the levels are lower than reference, and if the level(s) indicate the subject will benefit, administering a RANKL antagonist/inhibitor. Since the first step of claim 1 recites “determining…in a biological sample”, this clause is interpreted as requiring an active measuring step. The second step of comparing and the third step of determining whether or not the subject will benefit from treatment are mental steps and are therefore judicial exceptions. The judicial exceptions are based upon the relationship between AMH and inhibin B levels and the likelihood of whether the subject would benefit or not with treatment with a RANKL antagonist/inhibitor.
Independent claim 42 recites a conditional treatment to be administered if one of the listed endpoints are met. The claim does not require any active measuring step; rather, the claim encompasses reading the AMH and inhibin B levels off of a chart. Although the claim does not explicitly recite a comparison/determination step, this is implicit in the conditional nature of the treatment; namely a RANKL antagonist/inhibitor is administered if one of the four listed conditions are met. The judicial exception is decision of whether or not to treat based upon the AMH or inhibin B levels. In the cases of both independent claims 1 and 42, the mental step of comparing biomarker levels is similar to comparing information regarding a sample or test subject to a control or target data (see Univ. of Utah Research Found, v. Ambry Genetics Corp., 113 USPQ2d 1241 (Fed. Cir. 2014), or diagnosing an abnormal condition by performing clinical tests and thinking about the results (see In re Grams, 12 USPQ2d 1824 (Fed. Cir. 1989). The answer to Prong One of Step 2A is yes.
The second step in determining patent-eligibility of claimed subject matter is to consider whether the claims recite additional elements that integrate the judicial exception into a practical application (see Prong Two of Step 2A of the Guidelines). As noted above, claim 1 requires a measuring step. Dependent claims 31, 32 and 35 recite details about the biomarker measured and the cut-off values, however, these limitations merely provide more detail about the judicial exception, i.e., the relationship between AMH and Inhibin B levels (the biomarkers) and the likelihood of whether the subject would benefit or not with treatment with a RANKL antagonist/inhibitor. Claims 33 and 34 recite the types of assays that may be performed to measure the biomarkers; however, the measuring step is merely the necessary data gathering required in order to perform the mental analysis steps of comparison and determining. Dependent claims 36-40 broadly describe the RANKL antagonist/inhibitor, and claim 41 defines the subject as oligospermic, however, the administration step in claim 1 is conditional; the subject is only administered the treatment if he is determined to benefit therefrom based upon the comparison of the AMH or inhibin B levels.
Claim 42, in contrast, does not require an active step of measuring AMH or Inhibin B, and therefore encompasses reading results off a chart. Dependent claims 43-49 broadly describe the RANKL antagonist/inhibitor, though notably, independent claim 42 requires treatment only if one of the listed endpoints are met. Claim 42 encompasses an embodiment in which no treatment is administered, and only the mental analysis step is carried out. In summary, the judicial exceptions are not integrated into a practical application. In the case of claim 1 and its dependents, the measuring step is a necessary data-gathering step and the treatment step is conditional. In the case of claim 42 and its dependents, there are no required steps that integrate the judicial exception into a practical application. The answer to Prong Two of Step 2A is no.
The final step in determining whether the claims recite patent eligible subject matter is to consider whether they recite additional elements that amount to significantly more than the judicial exception. As noted above, the treatment steps in the claims are conditional. Further, regarding claim 1 and its dependents, the measuring AMH or Inhibin B steps may be carried out by well-known immunoassays (see claims 33 and 34). For instance, Nery et al. (Andrology, 2014, 2, 918-923—on IDS filed 05/14/2025) teach AMH and inhibin B was measured by ELISA (see p. 920, left column, under “Seminal plasma separation and hormone assays”). See also Illingworth et al. (Journal of Clinical Endocrinology and Metabolism 1996; 81: 1321-1325), who teach Inhibin B was measured by enzyme linked immunosorbent assay (see p. 1322, right column, 4th paragraph). The additional measuring step in claim 1 and its dependents are simply appending well-understood, routine and conventional activities previously known to the industry and specified at a high level of generality to the judicial exception (see MPEP 2106.05(d)). Regarding claim 42 and its dependents, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because other than the conditional treatment, there are no additional active steps. Thus, the claims do not include additional elements that are sufficient to amount to more than the judicial exception.
Note that this rejection could be overcome by amending the claims to affirmatively require treatment. For instance, claim 1 could be amended to recite something like treating a male subject suffering from infertility with a RANKL antagonist/inhibitor, wherein said male subject was determined to have an AMH level above 30 pmol/l in blood serum or above 5 pmol/l in seminal fluid.
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
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.
Claims 1 and 36-40 are rejected under 35 U.S.C. 103 as being unpatentable over Jensen et al. (Journal of Bone and Mineral Research, (DEC 2019) Vol. 34, No. Suppl. 1, pp. 193-194—on IDS filed 03/31/2023). Independent claim 1 recites a method for determining a likely effect of a treatment to improve male fertility comprising determining anti-Müllerian hormone (AMH) or Inhibin B level(s) in a biological sample from a male subject, comparing said determined AMH or Inhibin B level(s) to a corresponding reference level; and determining that said subject will either likely benefit from treatment with a RANKL antagonist/inhibitor if said level(s) is equal to or higher than said reference level or likely not benefit from treatment with a RANKL antagonist/inhibitor if said level is lower than said reference level, wherein if said subject is considered likely to benefit from treatment with an of RANKL antagonist/inhibitor, administering to said male subject a RANKL antagonist/inhibitor. Claims 36-40 recite the RANKL antagonist/inhibitor has binding affinity for RANKL (36), binds the same epitope as denosumab or osteoprotegerin (OPG—37), has a binding affinity similar to or higher than denosumab or OPG (38), is one of the types of antibodies recited in claim 39 or is denosumab or a fragment thereof (40).
The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. Jensen et al. teach treating “infertile men with 60mg RANKL-inhibitor denosumab once induced…the total number of progressively motile sperm”. Jensen et al. recognized, however, that the “beneficial effect was not observed in all men and was dependent on high serum OPG and Inhibin B levels prior to treatment”. See the body of the abstract. Regarding claims 37 and 38, the teaching of denosumab in Jensen and colleagues is an obvious variant of any RANKL antagonist/inhibitor encompassed by those claims. The second factor to consider is to ascertain the differences between the prior art and the instant claims. Jensen et al. do not explicitly teach they are determining the likely effect of a male fertility treatment. Nevertheless, Jensen et al. taught denosumab was beneficial in patients who were found to have high serum Inhibin B levels prior to treatment.
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the teachings of Jensen et al. by utilizing the knowledge therein to prescreen infertile males as candidates for denosumab treatment, because there are few available treatments for male infertility although “semen quality is part of the problem in 50% of [infertility] cases” (see first two sentences of Jensen and colleagues). The person of ordinary skill in the art would have been motivated to pre-screen candidates for denosumab treatment in order to avoid unnecessary ineffective treatment, since denosumab only benefited sperm motility in infertile males with high Inhibin B levels (see abstract body). Furthermore, the person of ordinary skill in the art could have reasonably expected success because denosumab was shown to be effective in this patient population.
Thus, the claims do not contribute anything non-obvious over the prior art.
Claims 33 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Jensen et al. as applied to claims 1 and 36-40 above, and further in view of Meachem et al. (European Journal of Endocrinology (2001) 145 561-571). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. The teachings of Jensen and colleagues and how they meet the limitations of claims 1 and 36-40 are outlined above in the preceding rejection and are hereby incorporated. The second factor to consider is to ascertain the differences between the prior art and the instant claims. Jensen et al. do not teach how the Inhibin B was measured in serum in their study. Meachem et al. teach measuring Inhibin B in serum with an ELISA (see p. 563, Figure 1).
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to measure Inhibin B in serum with an ELISA, as taught in Meachem et al. because they teach that the development of the then new ELISA for “specific measurement of bioactive Inhibin B” overcame previous shortcomings with Inhibin B measurement (see p. 562, left column, last paragraph of Meachem and colleagues). The person of ordinary skill in the art would have been motivated to use the ELISA taught by Meachem because it can distinguish between active and inactive forms (see p. 562, left column, last paragraph). Furthermore, for this reason as well, the person of ordinary skill in the art could have reasonably expected success.
Thus, the claims do not contribute anything non-obvious over the prior art.
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 1, 31-47 and 49 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the claimed methods in which the RANKL antagonist/inhibitor is denosumab, does not reasonably provide enablement for the claims as broadly recited. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” (See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 Fed. Cir. 1988). These factors include, but are not limited to: (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The claims encompass treatment of patients determined to likely benefit from treatment with a RANKL antagonist/inhibitor and are broad with respect to said RANKL antagonist/inhibitor. The specification discloses such antagonist/inhibitors in terms of function and ability to bind RANKL. See pages 19-20:
The antagonist or inhibitor of RANKL is a molecule having binding affinity for RANKL, such as wherein the RANKL binding moiety binds to soluble RANKL, such as binds to full length RANKL, or truncated versions of RANKL, such as binds to C-terminal or N-terminal truncated versions of RANKL, preferably binds to the C-terminal of RANKL.
In yet an embodiment, the antagonist or inhibitor of RANKL having binding affinity for RANKL, binds RANKL at the same epitope as Denosumab or OPG. In yet a further embodiment, the antagonist or inhibitor of RANKL having binding affinity for RANKL, binds RANKL with a binding affinity similar to Denosumab or OPG or with a binding affinity higher than Denosumab or OPG.
In yet a further embodiment, the antagonist or inhibitor of RANKL is selected from the group consisting of polyclonal antibody, a monoclonal antibody, an antibody wherein the heavy chain and the light chain are connected by a flexible linker, an Fv molecule, an antigen binding fragment, a Fab fragment, a Fab' fragment, a F(ab')2 molecule, a fully human antibody, a humanized antibody, a chimeric antibody and a single-domain antibody (sdAb) (nanobody), and small molecule inhibiting RANKL function.
The specification asserts there are known RANKL antagonists/inhibitors, but does not disclose any other than denosumab and osteoprotegerin (OPG). Nakai et al. (Bone Research (2019) 7:1) discloses the small molecule inhibitor AS2676293, which was shown to have potential as a cancer treatment (see abstract). In addition, the MedChemExpress website (https://www.medchemexpress.com/Targets/rankl-rank/effect/inhibitor.html, downloaded 12/11/2025; 3 pages total) discloses 19 RANK/RANKL inhibitors, most of which are small molecules. Nevertheless, the claims recite treatment of male infertility, and the specification only provides evidence that denosumab treats male infertility in a subset of infertile males with AMH or Inhibin B levels above certain cut-off values.
The specification teaches that denosumab increased fertility in males compared with placebo (see Example 1; p. 33, Figures 2-4) and this effect was most pronounced in men with high AMH levels (see Figure 5). The specification also discloses that “Inhibin B in serum prior to start of treatment is a biomarker for sperm quality” (see p. 39; also Figure 10):
This preliminary finding could indicate that the effect of Denosumab is dependent on specific baseline characteristics of the patients. Assessment of clinical and biochemical differences at baseline indicated that high serum AMH, Inhibin B, AMH/Inhibin B, RANKL/OPG ratio prior to treatment were the best predictor for a positive treatment response to Denosumab.
The post-filing date art by Andreassen et al. (Cell Reports Medicine (2024); 5, 101783) teaches that OPG administration did not result in statistically significant differences in germ cell proliferation in mouse ex vivo testis cultures (see p. 5, left column, 2nd paragraph), thereby suggesting that it is not predictable that any RANKL antagonist/inhibitor will behave in the same way. The evidence in the specification is not commensurate in scope with the breadth of the claims.
Insomuch as the claims encompass antibodies to RANKL (other than denosumab), truncated, soluble RANKL variants or OPG fragments or variants, the specification does not disclose the structure of such antibodies or protein variants capable of treating male infertility. The number of mutations generally possible in any given protein, for instance, RANKL or OPG, that can be made with a reasonable expectation of success are limited. Certain positions in the sequence are critical to the protein's structure/function relationship, e.g., such as various sites or regions directly involved in binding, activity and in providing the correct three-dimensional spatial orientation of binding and active sites.
The art provides evidence that mutations can be destabilizing and their effects unpredictable. Bhattacharya et al. (PLoS ONE 12(3): e0171355. https://doi.org/10.1371/journal.pone.0171355; 22 pages total) teach even single nucleotide variations have a “range of effects at the protein level that are significantly greater than assumed by existing software prediction methods, and that correct prediction of consequences remains a significant challenge” (p. 18, 1st and 2nd paragraphs). Although machine learning algorithms have improved the ability to predict protein 3D structure from sequences, methods based on artificial intelligence for predicting the impact of mutations on protein stability still face challenges, including prediction biases towards “generalization”, “data set”, “destabilizing mutations” and the inability to predict the effects of multiple mutations. See Figure 1, at p. 162 and the discussion at pages 165-166 of Pucci et al. (Current Opinion in Structural Biology 2022, 72: 161-168). Although the specification outlines art-recognized procedures for producing and screening for RANKL inhibitors and antibodies, this is not adequate guidance as to the nature of active derivatives that may be constructed, but is merely an invitation to the artisan to use the current invention as a starting point for further experimentation.
Due to the large quantity of experimentation necessary to generate and test RANKL antagonists/inhibitors for the ability to treat male infertility, the lack of direction/guidance presented in the specification regarding, and the absence of working examples directed to the same, the unpredictability of the effects of mutation on protein structure and function, and the breadth of the claims which fail to recite limitations on the RANKL antagonists/inhibitors, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Written Description
Claims 1, 31-47 and 49 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. This is a written description rejection.
The claimed methods encompass an embodiment of treating male infertility comprising administering to said male subject a RANKL antagonist/inhibitor. The claims recite that the RANKL antagonist/inhibitor is a molecule having binding affinity for RANKL (claims 36 and 44), binds RANKL at the same epitope as denosumab or OPG (epitope is interpreted as meaning “portion” in this context—claims 37 and 45), binds RANKL with a binding affinity similar to or higher than denosumab or OPG (claims 38 and 46), is an antibody as recited in claims 39 or 49 or active fragments or variants of OPG (clams 40 and 47). Thus, the claims encompass treatment with a genus of RANKL antagonists/inhibitors. To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The MPEP 2163(A) states “‘[a]n invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function.’” For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. (See MPEP 2163(II)(A)(3)(a)(i)).
In deciding whether the application complies with the written description requirement of 35 USC 112(a) or 35 USC 112 (pre-AIA ), first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. From the specification, it is clear that Applicant has possession of denosumab and OPG. The art also discloses small molecule RANKL inhibitors; see for example, the MedChemExpress website (https://www.medchemexpress.com/Targets/rankl-rank/effect/inhibitor.html, downloaded 12/11/2025; 3 pages total), which discloses 19 RANK/RANKL inhibitors. Nevertheless, neither the specification nor the art describes the genus of RANKL antibodies, truncated RANKL variants, or OPG fragments or variants having binding affinity for RANKL either similar to or higher than denosumab or OPG, binding at the same portion of RANKL as denosumab or OPG and that is capable of treating male infertility.
Regarding antibodies, it is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. The prior art teaches that small changes in the amino acid structure of the CDRs can have large effects on activity. For instance, Piche-Nicholas et al. (MAbs. 2018; 10: 81-94. doi: 10.1080/19420862.2017.1389355) teaches that the “binding affinity of IgG molecules…to FcRn that differed by only a few amino acid residues in CDRs revealed that small changes in CDRs, as minute as one amino acid residue change, could alter affinity to FcRn up to 79-fold.” See p. 89, right column, last paragraph of Piche-Nicholas et al.
In the instant case, the recitation in the claims of function alone to define the genus of RANKL antagonists/inhibitors, truncated RANKL variants, or OPG fragments or variants, namely: (1) having binding affinity for RANKL either similar to or higher than denosumab or OPG; (2) binding at the same portion of RANKL as denosumab or OPG and (3) capable of treating male infertility, is little more than a wish for possession and does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing “a result that one might achieve if one made that invention”); In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does “little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate”). Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). With the exception of denosumab and OPG, the skilled artisan cannot envision the detailed chemical structure of the encompassed RANKL antagonist/inhibitor, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, only denosumab or OPG, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675