DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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 Application, Amendments, and/or Claims
2. The preliminary amendment filed 02 April 2024 has been entered in full. Claims 1-6 and 9 have been amended, and claims 7, 10 and 12-13 have been canceled. Therefore, claims 1-6, 8-9 and 11 are pending and the subject of this Office Action.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on 26 February 2024 has been considered by the examiner.
Drawings
4. The Drawings are objected to because Figure 10 discloses amino acid sequences without an accompanying sequence identifier (i.e., SEQ ID NO: #). The SEQ ID NO: may be inserted into the Figure or the Brief Description of the Drawings. If the Sequence Identifiers are added to the Figures, corrected drawing sheets will be required in reply to the Office action to avoid abandonment of the application.
5. 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. The replacement sheet(s) should be labeled “Replacement Sheet” in the page header (as per 37 CFR 1.84(c)) so as not to obstruct any portion of the drawing figures. 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.
6. Furthermore, if the sequences are not present in the sequence listing, Applicant is required to provide (1) a substitute computer readable form (CRF) copy of a “Sequence Listing” which includes all of the sequences that are present in the instant application and encompassed by these rules, (2) a substitute paper copy of that “Sequence Listing”, (3) an amendment directing the entry of that paper into the specification, and (4) a statement that the content of the paper and computer readable copies are the same, and, where applicable, include no new matter, as required by 37 C.F.R. § 1.821 through 1.825. The claims and/or instant specification will also need to be amended so that it complies with 37 C.F.R. § 1.821(d) which requires a reference to a particular sequence identifier (i.e., SEQ ID NO: #) be made in the specification and claims wherever a reference is made to that sequence (See M.P.E.P. 2422.04). It is noted that Sequence identifiers can also be used to discuss and/or claim parts or fragments of a properly presented sequence. For example, language such as "residues 14 to 243 of SEQ ID NO:23" is permissible and the fragment need not be separately presented in the "Sequence Listing XML." See 37 CFR 1.831(c).
Claim Rejections - 35 USC § 112
7. 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.
8. Claims 2-5 are 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. From the specification it is presumed that the recited functions, i.e., “wherein the RGMc promotes development of ovarian follicles” (claim 2), “wherein the RGMc increases expression of one or more selected from the group consisting of Oct3/4, Nanog, and p63” (claim 3), “wherein the RGMc increases expression of one or more selected from the group consisting of Ptg, Edn2, and Hpgds” (claim 4) and “wherein the RGMc reduces expression of one or more selected from the group consisting of Tbxa2r, Oxtr, and Adra1d” (claim 5), can be attributed to the RGMc-derived protein as recited in claim 1. Therefore, claims 2-5 fail to further limit the claim from which they depend (claim 1) by altering the structure or adding additional components. 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 § 112
9. 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.
10. Claims 1-6 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.
11. Claim 10 is rejected as being indefinite because it is unclear if the limitation ‘administering a pharmaceutical composition comprising RGMc-derived protein” refers to administering it to any subject, or a subject with poor POR. It is thus unclear what the claimed method is intending to accomplish. Amending the claim to recite, for example, “A method for treating poor ovarian response syndrome (POR) in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an RGMc-derived protein” would be remedial.
12. Claims 2-6 are rejected for depending from an indefinite claim.
Claim Rejections - 35 USC § 112
13. 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.
14. Claims 1-6 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 methods of treating poor ovarian response syndrome (POR) in a subject in need thereof, comprising administering a pharmaceutical composition comprising an RGMc-derived protein, does not reasonably provide enablement for a method of preventing POR. 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 and/or use the invention commensurate in scope with these claims.
15. Factors to be considered in determining whether a disclosure enables one skilled in the art to make and use the claimed invention in its full scope without resorting to undue experimentation include: (1) the quantity of experimentation necessary; (2) the amount of direction or guidance presented; (3) the presence or absence of working examples; (4) the nature or complexity of the invention; (5) the state of the prior art; (6) the relative skill of those in the art; (7) the predictability or unpredictability of the art; and (8) the breadth of the claims. See In re Wands, 8 USPQ2d. 1400 (Fed. Cir. 1988).
16. In the instant case, the claims are broadly drawn to methods of preventing or treating poor ovarian response, comprising administering a pharmaceutical composition comprising an RGMc-derived protein. Thus the claims encompass complex and unpredictable subject matter, involving the effects of complex biological molecules on diseased physiological states. As was found in Ex parte Hitzeman, 9 USPQ2d 1821 (BPAI 1987), a single embodiment may provide broad enablement in cases involving predictable factors such as mechanical or electrical elements, but more will be required in cases that involve unpredictable factors such as most chemical reactions and physiological activity. However, this invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology”, Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). See also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir.), cert, denied, 502 U.S. 856 (1991).
17. While the Specification teaches that administration of RGMc significantly increased preantral and antral follicles (See Example 2); increased levels of Oct3/4and Nanog, known to improve survival of primordial follicles (See Example 3); promotes follicular development through increases Edn2 and Hpdgs levels (See Example 5); and increases PGD2 levels, known to support follicular development, in cumulus cells from both POR and normal subjects (See Example 7), the data presented in the Specification does not rise to the level of prevention. The term “prevent” is interpreted as meaning that an activity will not occur, i.e. poor ovarian response will not occur. However, the art clearly recognizes known tests have little clinical value in predicting poor ovarian response (See Badawy et al. J. Reprod. Infertil. 12(4):241-248, published 2011). Therefore, while administration of the RGMc protein would be expected to treat poor ovarian response in a subject in need thereof, one skilled in the art would not predict that it would prevent the occurrence of said condition since there are no known predictors of said condition. There are no working examples provided in the instant application which demonstrate that administration of RGMc prevents the occurrence of poor ovarian response in a subject, and undue experimentation would be required of the skilled artisan to identify a subject with the risk of developing the condition, determine the quantity of RGMc to be administered, as well as the timing and duration of treatment to prevent poor ovarian response in a subject.
Claim Rejections - 35 USC § 101
18. 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.
19. Claims 8-9 and 11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature-based product without significantly more. The claim(s) recite(s) a pharmaceutical composition comprising an RGMc-derived protein. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the proteins are a nature-based product, and as indicated supra, the intended uses have not been given patentable weight, as they do not result in a structural difference of the proteins.
20. Applicant’s attention is directed to the USPTO January 7, 2019 Revised Patent Subject Matter Eligibility Guidance (i.e. Guidance) available at URL:
https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf.
21. The guidance addresses the impact of Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S._, 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013) (Myriad) on the Supreme Court’s long-standing “rule against patents on naturally occurring things”, as expressed in its earlier precedent including Diamond v. Chakrabarty, 447 U.S. 303 (1980) (Chakrabarty), and Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. _, 132 S. Ct. 1289, 101 USPQ2d 1961 (2012) {Mayo). See Myriad, 133 S. Ct. at 2116. Myriad relied on Chakrabarty as “central” to the eligibility inquiry, and re-affirmed the Office’s reliance on Chakrabartys criterion for eligibility of natural products (i.e., whether the claimed product is a non-naturally occurring product of human ingenuity that is markedly different from naturally occurring products). Id. at 2116-17. Myriad also clarified that not every change to a product will result in a marked difference, and that the mere recitation of particular words (e.g., “isolated”) in the claims does not automatically confer eligibility. Id. at 2119. See also Mayo, 132 S. Ct. at 1294 (eligibility does not “depend simply on the draftsman’s art”). Thus, while the holding in Myriad was limited to nucleic acids, Myriad is a reminder that claims reciting or involving natural products should be examined for a marked difference under Chakrabarty.
22. In Mayo Collaborative Services v. Prometheus Laboratories, Inc. (Mayo) 101 USPQ2d 1961,1965-1966 (SC 2012) it was stated:
“Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U. S. 63, 67 (1972). And monopolization of those tools through the grant of a patent might tend to impede innovation more than it would tend to promote it. (Emphasis added)
Still, as the Court has also made clear, to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words “apply it.”
Our conclusion rests upon an examination of the particular claims before us in light of the Court’s precedents. Those cases warn us against interpreting patent statutes in ways that make patent eligibility “depend simply on the draftsman’s art” without reference to the “principles underlying the prohibition against patents for [natural laws].” Flook, supra, at 593. They warn us against upholding patents that claim processes that too broadly preempt the use of a natural law. Morse, supra, at 112-120; Benson, supra, at 71-72. And they insist that a process that focuses upon the use of a natural law also contain other elements or a combination of elements, sometimes referred to as an “inventive concept,” sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the natural law itself. Flook, supra, at 594; see also Bilski, supra, at_(slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by attempting to limit the use of the formula to a particular technological environment’ or adding ‘insignificant post solution activity’” (quoting Diehr, supra, at 191-192)). (Emphasis added)
We find that the process claims at issue here do not satisfy these conditions, in particular, the steps in the claimed processes (apart from the natural laws themselves) involve well-understood, routine, conventional activity previously engaged in by researchers in the field. At the same time, upholding the patents would risk disproportionately tying up the use of the underlying natural laws, inhibiting their use in the making of further discoveries. (Emphasis added)
23. Regarding Step 1 of the Guidance, the claims are directed to the statutory category of a product.
24. Regarding Step 2A, prong one, the claims are directed to and recite the judicial exception of a nature-based product. The instant claims are directed to compositions of matter consisting of a protein. The claimed proteins are naturally occurring proteins, or a fragment thereof, therefore, they are considered a nature-based product, which is a judicial exception.
25. Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application. There are no additional elements recited in the claims
26. Regarding Step 2B, the next question is whether the remaining elements/steps -i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception. Here, the claims as a whole are not considered to recite any additional steps or elements so as to render the claims patent-eligible.
The additional elements recited in claims 8-9 and 11 are nothing other than intended uses, which are not given patentable weight. Under the holding of Myriad, the claimed proteins are not eligible because they are not different enough from what exists in nature to avoid improperly tying up the future use and study of the individual components of the formulations. Accordingly, the claims are directed to a judicial exception. Because the claims do not include any additional features that could add significantly more to the exception, the claims do not qualify as eligible subject matter.
27. For the reasons set forth above, when the claim is considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 102
28. 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.
29. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
30. Claim(s) 8-9 and 11 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Lin et al. (US Pat. No. 8,895,002; issued 25 November 2014).
31. Lin et al. discloses a human HJV (i.e., RGMc) protein having the amino acid sequence of SEQ ID NO: 2, as well as fragments thereof, and disclose pharmaceutical compositions comprising said proteins (See , as well as claudin proteins, including the Claudin-5 protein (See Column 2, claims 1-23). Applicants are advised that the limitations “or preventing, treating or ameliorating infertility”, “wherein the infertility is infertility due to poor ovarian response syndrome”, and “for promoting pregnancy” have not been given patentable weight as they are an intended use (See In re Ngai, 367 F.3d 1336, 70 USPQ2d 1862 (Fed. Cir. 2004); MPEP 2111.02II). A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the limitations of the claim (See MPEP 2111.02II). Therefore, the reference of Lin et al. meets all the limitations of claims 8-9 and 11.
Summary
32. No claim is allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JON M LOCKARD whose telephone number is (571) 272-2717. The examiner can normally be reached M-F 9-6 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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached on (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JON M LOCKARD/Examiner, Art Unit 1647 August 7, 2026
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