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 .
Election/Restrictions
Applicant’s election of Group II, claims 4 and 6-8 in the reply filed on 10/21/25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 12-14 were previously canceled. Currently, claims 1-11 and 15-23 are pending. Claims 1-3, 5, 9-11 and 15-23 are withdrawn as being directed to non-elected inventions. Accordingly, claims 4 and 6-8 are under examination.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The instant abstract utilized implied phrases see “The present invention relates to”. This language should be avoided.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
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.
Written Description
Claims 4 and 6-8 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 4 is directed to endothelial protein C receptor (EPCR) or an lysobisphosphatidic acid (LBPA)-binding fragment thereof that has the unique capability of binding to LBPA.
Claim 4 as a whole therefore encompasses a genus of proteins and fragments defined by reference to a desired functional characteristic, namely the capacity to bind to LBPA.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
The genera encompassed by the claims are of large size and substantial variability. For example, claim 4 encompasses any and all EPCR protein or fragments binding fragments thereof. As a result, the number of species meeting the structural requirements of the claim is exceedingly large and characterized by substantial variability; in that any protein or fragment thereof of EPCR would be encompassed. For instance, the current claims encompass EPCR polypeptides (proteins) or peptides which may have any number of amino acids added wherein the amino acids can be added in any order or combination or may have any deletion or substitution within EPCR. The claims allows this diverse number of amino acids added to, deleted or substituted in any combination. It is not apparent that the identities of all such species could be determined even with the aid of a computer.
Furthermore, only those sequences meeting the structural and functional requirements of the genus are encompassed by the claim. Therefore, the claims encompass all of the sequences meeting the structural requirements that are also able to bind to an autoantibody. In this case, however, it cannot be envisioned based on the specification what sequences would possess such binding properties.
Comparing the claim scope with the scope of the description, it is noted that the specification as filed does not provide the structure or sequence of a single EPCR fragment which possesses the unique capability of binding to LBPA. Further, the binding of EPCR to LBPA is not well known in the art. The specification on page 3 discloses that the inventors surprisingly identified LBPA and the presentation thereof by EPCR. Page 3 also discloses that the inventors were able to show that the interaction of EPCR and LBPA is critical for the course of antiphospholipid syndrome. The, the only examples in the specification which provide the unique characteristic of binding to LBPA is the EPCR protein.
It was known in the prior art that small changes in antigen structure profoundly affect antibody-antigen interactions. Harlow & Lane (Harlow, E. and Lane, D., Antibodies: A Laboratory Manual (1988) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pages 23-26) discuss how even small changes in antigen structure can profoundly affect the strength of an antibody-antigen interaction. See entire selection, in particular page 26, first full paragraph. In particular, the loss of a single hydrogen bond can reduce the strength of interaction by 1000-fold (ibid).
Many other researchers have reported similar findings to those of Harlow & Lane. For example, Lederman et al. ("A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4" Mol Immunol. 1991 Nov;28(11):1171-81) found that a single amino acid substitution on the antigen CD4 ablated binding of a monoclonal antibody (see title and abstract). Similarly, Colman et al. (Research in Immunology, 1994; 145(1): 33-36) teach that amino acid changes in an antigen can effectively abolish antibody antigen binding entirely (see entire document, particularly pages 33-34).
As noted above, the variability among the peptides encompassed by the claims is also enormous; and would encompass changes much more substantial than the loss of a single hydrogen bond or the mutation of a single amino acid; yet even such minor changes as these were known to dramatically affect function.
Given the unpredictability associated with making even minor changes to antigen structure while preserving function, with limited exception it is not possible to predict which, out of the enormous number of peptides encompassed by the claims, would be capable of binding to an immunoglobulin and/or an immunoglobulin complex.
For all of these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Written Description
Claims 4 and 6-8 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to a method for identifying an inhibitor of endothelial protein C receptor (EPCR) function in any and all autoimmune disease. The limitation ‘autoimmune disease’ represents a genus and encompasses Systemic Lupus, Scleroderma, Multiple Sclerosis, Psoriasis, Sjogrens Syndrome, Vitiligo, Graves disease, Polymyositis, Microscopic Colitis, Rheumatoid arthritis, Kawasaki disease and Urticaria to name a few. However, there is inadequate written description in the instant specification for a method of such broad scope as claimed currently.
In order to fulfill the written description requirements set forth under 35 U.S.C § 112, first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, each member correlated with the requisite function, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicants have possession the claimed invention. Applicants have not described and established structure-function correlation for a representative number of species within the broad genus of at least the recited ‘autoimmune disease’, such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the full scope of the claimed invention at the time the application was filed.
The purpose of the written description requirement is ‘to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.’ In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978). Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. When there is substantial structural variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
A review of the instant specification indicates the following. The specification on pages 1 and 3 discloses a correlation of LBPA bound to EPCR and the detection of antiphospholipid antibodies (aPL) in subject having antiphospholipid syndrome. The examples in the specification are limited to the detection of aPL by LBPA-EPCR. The specification has not provided data, tables, figures or evidence that LBPA-EPCR which is present in antiphospholipid syndrome and specifically binds to antiphospholipid antibodies is also present in any and all other autoimmune diseases and specifically provides for detection of all autoantibodies and is correlated with any and all autoimmune diseases. The specification on page 3 discloses that the inventors surprisingly identified LBPA and the presentation thereof by EPCR. Page 3 also discloses that the inventors were able to show that the interaction of EPCR and LBPA is critical for the course of antiphospholipid syndrome. The examples in the specification are limited to antiphospholipid syndrome. The specification does not disclose that LBPA-EPCR which appears antiphospholipid syndrome subjects also appear in all other autoimmune diseases and that the LBPA-PCR provides bindings to any and all autoantibodies or proteins in any and all autoimmune disease subjects.
It must be noted that "[t]he applicant must . . . convey to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention." Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir.1991). The invention, is for purposes of the ‘written description’ inquiry, whatever is now claimed.” See page 1117. The specification does not describe the claimed embodiments in sufficient detail to convey to a person skilled in the art that Applicants were in possession of the full scope of the claimed invention at the time of filing. The Written Description Guidelines state: There is an inverse correlation between the level of predictability in the art and the amount of disclosure necessary to satisfy the written description requirement. For example, if there is a well-established correlation between the structure and function in the art, one skilled in the art will be able to reasonably predict the complete structure of the claimed invention from its function. Furthermore, the written description provision of 35 U.S.C § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, ‘Written Description’ Requirement (66 FIR 1099-1111, January 5,2001) state, ‘[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention’ (Id. at 1104). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. Factual evidence of an actual reduction to practice has not been disclosed in the instant specification, nor has Applicant shown the invention was ‘ready for patenting’. The Guidelines further state, ‘[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus' (Id. at 1106). 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. Instant claims are viewed as not meeting the written description provision of 35 U.S.C § 112, first paragraph. The specification fails to disclose the identifying an inhibitor of endothelial protein C receptor (EPCR) function in any and all autoimmune diseases.
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 4 and 6-8 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.
Claim 4 is vague and indefinite because it is unclear if the LBPA is a part of the sample, if the LBPA is added as a reagent or if the applicant intends something else. The current claim requires testing binding of LBPA to EPCR protein which is contained in the biological sample. However, the currently recited claim does not make clear if the LBPA is another molecule contained within the sample, if the LBPA is prebound to the EPCR, if the LBPA is added as a reagent or test compound of if the applicant intends something else. Applicant is reminded that although the claims are read in light of the specification limitations from the specification are not read into the claims. Please clarify.
Claim 4 is vague and indefinite because the claim is directed to a method for identifying an inhibitor of EPCR. However, the claim as currently recited allows for a scenario wherein binding of LBPA to EPCR is tested in the absence of the inhibitor. Thus, it is unclear how an inhibitor is identified in the current method when the inhibitor is absent from the test method. Please clarify.
Claim 8 is indefinite in reciting improper Markush language in reciting, “said potential inhibitor is selected from” because it appears to intend to limit the scope of the inhibitor in the claims but improperly defines it as such. Perhaps, Applicant intends “said potential inhibitor is selected from the group consisting of..”.
Allowable Subject Matter
Claims 4 and 6-8 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(a), and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action. The prior art of record does not teach nor fairly suggest contacting a potential inhibitor with the sample and testing binding of LBPA to EPCR as currently recited.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Santos et al (US 2007/0414625) discloses methods for detecting autoantibodies against EPCR (e.g. abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY W COUNTS whose telephone number is (571)272-0817. The examiner can normally be reached M-F 7:00-4:00.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678