DETAILED ACTION
Examiner acknowledges receipt of the reply filed 1/26/2026, in response to the restriction requirement mailed 11/26/2025.
Claims 27-44 are pending. Claims 29 and 38 are withdrawn from further prosecution for the reasons set forth herein.
Claims 27, 28, 30-37, and 39-44 are being examined on the merits in this office 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 I (claims 27-35) without traverse in the reply filed on 1/26/2026 is acknowledged.
Upon further consideration of the claims and claim scope, Group II (claims 36-44) is rejoined herein. The restriction requirement between Groups I and II as set forth in the restriction mailed 11/26/2025 is withdrawn.
Applicant’s election of the following species without traverse in the reply filed on 1/26/2026 is acknowledged:
Biomarker: FHR1
Species of degeneration: age-related macular degeneration (AMD)
Polypeptide or NA: polypeptide, SEQ ID NO:146
Claims 29 and 38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/26/2026.
Claims 27, 28, 30-37, and 39-44 read on the elected species.
Priority
The filing receipt dated 8/24/2023 provides the following priority information:
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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.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See e.g. specification filed at 1/26/2026 pp. 109, 117, 120, and 122.
Claim Objections
Claims 27, 28, 32, 34-37, and 39-42 are objected to because of the following informalities:
Claim 27 should be amended to recite “A method of treating a macular degeneration in a subject in need thereof, the method comprising:
(a)… a [[the]] level of one or more proteins selected from the group consisting of…
(b) … the level of the one or more proteins the one or more proteins
(c) administering to administering to , or a combination thereof”.
Regarding claims 28 and 37, please remove the single quotation marks around the claim terms wet and dry.
Claims 32 and 39 should be amended to recite “a [[the]] level of 2 or more ..FHR5, , or a combination thereof.”
Regarding claims 34 and 41, should be amended to recite “comprises determining a [[the]] level”. The respective claims should be split into 2 separate claims. The optional clause should be rewritten as a new dependent claim.
Claims 35 and 42 should be amended to recite “wherein step (a) one of:”.
Claim 36 should be amended to recite “A method of treating a macular degeneration in a subject in need thereof, acid…FHR4, , or a combination thereof;
(a)… a [[the]] level of one or more proteins selected from the group consisting of…
b) … the level of the one or more proteins the one or more proteins
Claim 40 should be amended to recite “level of FHR4”.
Appropriate correction is required.
Examiner recommends that claims 27 and 36, respectively, be split into two separate claims. Claims 27 and 36 recite two distinct treatment regimen end-points, treating protein/ nucleic acid comprising at least 85% identity to SEQ ID NO:146 vs non-related nucleic acid that reduces expression of a recited complement protein (FHR1-5).
Claims 27 and 36 should further be amended to recite “therapeutically effective amount” to provide a correlation between an amount of the claimed agent sufficient to provide treatment of any macular degeneration in the subject.
Applicant is advised that should claims 27-35 be found allowable, claims 36-44 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claims 27 and 36 recite the same limitations of a method of treating macular degeneration the subject in which a blood or liver sample from a subject has been assessed to determine the level of a recited complement factor, a high level as compared to a control subject indicates macular degeneration, and administration of either therapeutic agent of at least 85% identity to SEQ ID NO:146 or nucleic acid that reduces expression of one or more of the recited complement factors.
Sequence Interpretation/Claim Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising an amino acid sequence of SEQ ID NO: 1” requires only a dipeptide or more within SEQ ID NO: 1, “comprising the amino acid sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with or without additional amino acids at any N-/C-terminal ends or additional nucleotides at 5' /3' ends, “consisting of an amino acid sequence of SEQ ID NO: 1” would encompass any sequence of two or more consecutive amino acids (dipeptide or more) fully contained within SEQ ID NO: 1, and “consisting of the amino acid sequence of SEQ ID NO: 1” would be limited to the sequence of the amino acids as specified by SEQ ID NO: 1, and nothing more or less; "an amino acid selected from the group consisting of SEQ ID NOs: 1, 2 and 3” is any sequence of two or more consecutive amino acids (dipeptide or more) fully contained within SEQ ID NO: 1, 2 or 3; and “the amino acid selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 27, 28, 30-37, and 39-44 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 courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In this case, claim 27 is directed to a method of treating a macular degeneration in a subject, the method comprising:(a) determining in a blood-derived or liver sample obtained from the subject the level of one or more of Complement Factor H related protein 1 (FHR1),Complement Factor H related protein 2 (FHR2),Complement Factor H related protein 3 (FHR3), and/or Complement Factor H related protein 5 (FHR5), optionally in combination with Complement Factor H related protein 4 (FHR4), Complement Factor H-like protein 1 (FHL-2), and/or Complement Factor H (FH); (b) determining that the subject has or is likely to develop a macular degeneration if the level of the protein(s) in (a) is elevated as compared to the level of that protein(s) in blood or liver tissue in a control subject that does not have a macular degeneration; and (c) treating the subject with a therapeutic agent that comprises or encodes a polypeptide comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO:146, wherein the polypeptide has a total length of 450 amino acids or fewer; and/or treating the subject with a nucleic acid agent that reduces expression of one or more of FHR1, FHR2, FHR3, FHR4, and/or FHR5. Claim 36 is directed to a method of treating a macular degeneration in a subject, the method comprising administering to the subject a therapeutic agent that comprises or encodes a polypeptide comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO:146, wherein the polypeptide has a total length of 450 amino acids or fewer; and/or administering to the subject a nucleic acid agent that reduces expression of one or more of FHR1, FHR2, FHR3, FHR4, and/or FHR5; wherein the subject has been determined to have or be likely to have a macular degeneration by: (a) determining in a blood-derived or liver sample obtained from the subject the level of one or more of FHR1, FHR2, FHR3, and/or FHR5, optionally in combination with FHR4, FHL-1 and/or FH; (b) determining that the subject has or is a likely to have a macular degeneration if the level of the protein(s) in (a) is elevated as compared to the level of that protein(s) in blood or liver tissue in a control subject that does not have a macular degeneration.
The claims are drawn to a therapeutic agent comprising a polypeptide with at least 85% sequence identity to SEQ ID NO:146 (elected species). The specification indicates that SEQ ID NO:146 correlates with amino acid positions 491-684 of human complement receptor 1 (p. 83). The specification is limited to a polypeptide having 100% identity with instant SEQ ID NO:146. The specification does not clearly define or provide examples of what qualify as polypeptides of the claimed invention, having therapeutic value in the claims method of treating macular degeneration.
Claims 27 and 36 do not expressly recite that a therapeutically effective amount of the claimed therapeutic agent and/or nucleic acid agent is administered to the subject. Specifically, the claims do not recite any amount at all.
As stated earlier, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic.
SEQ ID NO:146 was not reduced to practice in examples 1-5 of the specification. Moreover, there are no examples of treating macular degeneration.
The specification is limited to a polypeptide having 100% identity with instant SEQ ID NO: 46. SEQ ID NO:146 is 194 amino acids in length. 85% sequence identity to SEQ ID NO:146 allow allows for up to 29 amino acid changes (e.g., substitution, insertion, deletion, or any combination thereof). There are 20 naturally occurring amino acids. Thus, there are 2820 (or 8.77 x1028) potential polypeptides within the instant claim scope polypeptides having at least 85% identity to SEQ ID NO:146. The actual number of variants is much higher when one considers non-naturally occurring amino acids.
As noted above, the specification is limited to a single polypeptide having 100% identity. No polypeptides were reduced to practice in the specification. There is not a sufficient amount of guidance provided to encompass the numerous characteristics of the whole genus claimed. The skilled artisan cannot extrapolate from a single to the numerous polypeptides that fall within the instant claim scope.
Additionally, the skilled artisan is not provided any guidance as to the amount of the claimed polypeptide of SEQ ID NO:146 that would be sufficient to effectively treat a subject with macular degeneration.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claims 27, 28, 30-37, and 39-44 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 treating macular degeneration comprising a polypeptide of SEQ ID NO:146, does not reasonably provide enablement for preventing macular degeneration. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed more recently in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (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. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
Breadth of claims. Claim 27 is directed to a method of treating a macular degeneration in a subject, the method comprising:(a) determining in a blood-derived or liver sample obtained from the subject the level of one or more of Complement Factor H related protein 1 (FHR1),Complement Factor H related protein 2 (FHR2),Complement Factor H related protein 3 (FHR3), and/or Complement Factor H related protein 5 (FHR5), optionally in combination with Complement Factor H related protein 4 (FHR4), Complement Factor H-like protein 1 (FHL-2), and/or Complement Factor H (FH); (b) determining that the subject has or is likely to develop a macular degeneration if the level of the protein(s) in (a) is elevated as compared to the level of that protein(s) in blood or liver tissue in a control subject that does not have a macular degeneration; and (c) treating the subject with a therapeutic agent that comprises or encodes a polypeptide comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO:146, wherein the polypeptide has a total length of 450 amino acids or fewer; and/or treating the subject with a nucleic acid agent that reduces expression of one or more of FHR1, FHR2, FHR3, FHR4, and/or FHR5.
Claim 36 is directed to a method of treating a macular degeneration in a subject, the method comprising administering to the subject a therapeutic agent that comprises or encodes a polypeptide comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO:146, wherein the polypeptide has a total length of 450 amino acids or fewer; and/or administering to the subject a nucleic acid agent that reduces expression of one or more of FHR1, FHR2, FHR3, FHR4, and/or FHR5; wherein the subject has been determined to have or be likely to have a macular degeneration by: (a) determining in a blood-derived or liver sample obtained from the subject the level of one or more of FHR1, FHR2, FHR3, and/or FHR5, optionally in combination with FHR4, FHL-1 and/or FH; (b) determining that the subject has or is a likely to have a macular degeneration if the level of the protein(s) in (a) is elevated as compared to the level of that protein(s) in blood or liver tissue in a control subject that does not have a macular degeneration.
The specification states at p. 31: “Treatment” may refer to treating or preventing a complement-related disorder, such as those described herein. The specification further states:
As used herein, ‘treatment’ may, for example, be reduction in the development or progression of a disease/condition, alleviation of the symptoms of a disease/condition or reduction in the pathology of a disease/condition. Treatment or alleviation of a disease/condition may be effective to prevent progression of the disease/condition, e.g. to prevent worsening of the condition or to slow the rate of development. In some embodiments treatment or alleviation may lead to an improvement in the disease/condition, e.g. a reduction in the symptoms of the disease/condition or reduction in some other correlate of the severity/activity of the disease/condition. Prevention/prophylaxis of a disease/condition may refer to prevention of a worsening of the condition or prevention of the development of the disease/condition, e.g. preventing an early stage disease/condition developing to a later, chronic, stage.
Given the broadest reasonable interpretation, prevention of a macular degeneration encompasses complete inhibition of the onset of a macular degeneration.
(2) The nature of the invention and predictability in the art: The invention is directed toward and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
(3) Direction or Guidance: That provided is limited. There are no examples of prevention of macular degeneration.
In order to prevent a macular degeneration, the skilled artisan must be able to first predict and identify subjects that are at risk for developing a macular degeneration, as well as required dosage amounts and routes of administration of a therapeutic agent that comprises or encodes a polypeptide comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO:146 in order to prophylactically treat [inhibit] development of a macular degeneration in a subject. As noted above, the full scope of the instant claim scope encompasses complete “prevention” in any and all subjects.
(4) State of the Prior Art: the following is a selection of articles relating to the instant claim scope.
McHarg et al. (Mol Immunol 67:43-50 (2015)) teach that age-related macular degeneration (AMD) is a leading cause of visual impairment. It is characterized by damage to a tissue complex composed of the retinal pigment epithelium, Bruch's membrane and choriocapillaris. In early AMD extracellular debris including drusen accumulates in Bruch's membrane and then in late AMD geographic atrophy and/or neovascularization develop. Variants in genes encoding components of the alternative pathway of the complement cascade have a major influence on AMD risk, especially at the RCA locus on chromosome 1, which contains CFH and the CFHR genes (abstract). Thus, genetics can influence development of macular degeneration.
Clark et al (J. Clin Med 4:18-31 (2015)- cited in IDS filed 12/27/2023)) teach macular degeneration (AMD) genetics has demonstrated that genetic alterations affecting the alternative pathway of the complement cascade have a major influence on AMD risk. One of the two most important genetic loci is on chromosome 1 and contains genes encoding complement factor H (FH) and the factor H related proteins (FHR proteins). In macular tissue, especially Bruch’s membrane, relatively high levels of a truncated splice variant of FH called factor H-like protein 1 (FHL-1) are present (abstract). Factor H (FH) is a blood borne glycoprotein that is also produced locally by the RPE, and functions as a deactivator of the complement system. Although it can act in the fluid phase its main role is to bind to host surfaces and protect them against complement activation. FH consists of 20 complement control protein (CCP) domains and there is a splice variant of FH called factor H-like protein 1 (FHL-1) that contains the first 7 CCPs of FH and then a unique 4 amino acid carboxy-terminal tail. FH (and FHL-1) acts primarily on the alternative complement pathway. It can disassociate factor B (FB; sometimes referred to as BbBa) from C3b on host surfaces thereby preventing the amplification of C3b deposition (see Figure 2C). In addition, it acts as a cofactor for FI. FI inactivates C3b by cleaving it to form inactive C3b (iC3b), but this requires the cofactor activity of FH or cell-surface bound complement regulators including complement receptor 1 (CR1) or the membrane cofactor protein (CD46). While both CR1 and CD46 play perhaps the more important role in protecting host cells from inappropriate complement attack, FH is the only regulator of complement to protect the extracellular matrix (ECM) (see Fig 2) (p 20). Dysregulation of complement in and around Bruch’s membrane brought about by insufficient binding of the regulators FHL-1 and FH and potentially compounded by an age-related loss in HS will lead to increased complement turnover, release of anaphylatoxins and a chronic local inflammatory response that may eventually result in visual loss from AMD (p. 26).
(5) Working examples:
Example 1 discloses preparation of peptides from complement proteins for mass spectrometry. GluC digestion was performed on FH, FHL-1, FHR1-5, FI, C3, C3b and C3b breakdown products to achieve distinct peptides for mass spectrometry. Specific peptides of the respective complement proteins are identified in table 1-5.
Example 2 discloses preparation of samples for LC-MS/MS. Results are disclosed in table 7.
Example 3 discloses detection of the complementome in age-related macular degeneration patients. See Table 2 (in Example 3) data indicating genetic markers.
Example 4 relates to tumor cell IDO enhances immune suppression and decreases survival Independent of tryptophan metabolism and glioblastoma; not pertinent to the instant claims encompassing macular degeneration.
Example 5 relates to COVID-19 patients, not pertinent to the instant claims encompassing macular degeneration.
There are no examples administering a polypeptide encompassing SEQ ID NO:146, much less a nucleic acid encoding the polypeptide. There are no examples of prophylactic treatment [prevention] of a macular degeneration comprising a therapeutic agent comprising the polypeptide having at least 85% sequence identity to SEQ ID NO:146. Prevention of a macular degeneration is construed as preventing the underlying genetic components that contribute to disease onset. There is no evidence of record that administering the polypeptide of SEQ ID NO:146 would eliminate [prevent] onset of macular degeneration. As noted in the cited references, multiple genes have been shown to be associated with macular degeneration.
(6) Skill of those in the art:
An ordinary artisan in the area of drug development would have experience in screening peptide compounds for particular activities. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against particular biological target is well known. Additionally, while high throughput screening assays can often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems such as the eye.
MPEP 2141.03 states (in part)" A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. V. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. At 1396, 82 USPQ2d at 1396. The "hypothetical person having ordinary skill in the art' to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art." Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner's definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
(7) The quantity of experimentation needed: given the fact that, historically, the development of new drugs has been difficult and time consuming, and especially in view of factors 1-6, the quantity of experimentation needed is expected to be substantial and undue.
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
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 27, 28, 30-37, and 39-44 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.
The metes and bounds of claim 27 are indefinite following reasons:
Claim 27, part (a) recites the limitation "the level". There is insufficient antecedent basis for this limitation in the claim.
Claim 27, part (b) recites the limitation "the protein(s)". There is insufficient antecedent basis for this limitation in the claim. Part (a) refers to one or more recited proteins. It is further unclear as to the identity of the protein which is referred back to by the limitation “that protein”.
The preamble of claim 27 recites: a method of treating a macular degeneration the subject. Part (c) recites treating the subject with a therapeutic agent …; and/or treating a subject with a nucleic acid agent. The recitation of “treating” in part (c) does not actively set forth and delimit how the step is actually practiced, or how this relates back to the preamble “method of treating”.
In contrast, an active step of administering the claimed therapeutic agent and/or nucleic acid agent to the subject more precisely set forth in active step.
Because claims 28 and 30-35 depend from indefinite claim 27 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
Examiner recommends that part (a) recite “a level”; part (b) be amended to recite “level of the one or more proteins the one or more proteins administering to
Regarding claims 28 and 37, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 28 and 37 recite the broad recitation “age related macular degeneration”, and the claim also recites “Geographic Atrophy (‘dry’ or non-exudative AMD), early AMD, intermediate AMD, late/advanced AMD, ‘wet’ (neovascular or exudative) AMD” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The metes and bounds of claims 31 and 44 are deemed to be indefinite. Claims 31 and 44 recites “digesting at least one of the protein(s) in the sample”. Independent claims 27 and 36 refer back to a blood-derived or liver sample comprising the one or more recited proteins. There is no indication in the claims or specification that the recited one or more proteins of part (a) have been isolated from the sample prior to digesting. Specifically, when there ordinary skill the art would understand that the blood or liver sample contains proteins which are not complement proteins. Therefore, it is not clear if, for example, if the entire sample and proteins there is digested; OR the at least one recited [complement] protein is removed from the sample and then digested.
This also applies to parts (ii)-(iii) of the respective claims. The exact identity of “one or more peptides” and the identity of the proteins they derived from is unclear.
Regarding claims 31 and 44, the limitation "the sample". There is insufficient antecedent basis for this limitation in the claims. Respective independent claims 27 and 36 refer to blood-derived or liver sample.
Please amend claims 31 and 44 to more precisely define “the protein(s)”, “the sample”, and “one or more peptides” and the interrelatedness on these claim terms.
The metes and bounds of claims 34 and 41 are deemed to be indefinite. Claims 34 and 41 recite “optionally determining … the level of FHL-1 in blood”. Independent claims 27 and 36 recites that the sample is a blood-derived or liver sample. It is unclear if the standard for comparison, as relating to determining FHL-1 level, is limited to blood.
To overcome this rejection, examiner recommends striking through the phrase “in blood”.
The metes and bounds of claim 96 are indefinite for the following reasons:
Claim 36, part (a) recites the limitation "the level". There is insufficient antecedent basis for this limitation in the claim.
Claim 36, part (b) recites the limitation "the protein(s)". There is insufficient antecedent basis for this limitation in the claim. Part (a) refers to one or more recited proteins. It is further unclear as to the identity of the protein which is referred back to in by limitation “that protein(s)”.
Because claims 37 and 39 - 44 depend from indefinite claim 36 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
To overcome the rejection, Examiner recommends that part (a) recite “a level”; and part (b) be amended to recite “level of the one or more proteins the one or more proteins
Claim Rejections - 35 USC § 102
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.
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)(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.
Claims 27, 28, 30-37, and 39-44 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated Bishop (U.S. 20230400470; correlates with Appl. No. 18052795, ODP rejection). The earliest effective filing date is 5/07/2020.
The applied reference has a common applicant/inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding claims 27 and 36, Bishop teaches a method of treating a complement-related disorder (e.g. macular degeneration) in a subject, the method determining the level of one or more of FHR1, FHR2, FHR3, FHR4, FHR5, FHL1, and/or FH compared to reference value(s) obtained previously from the same subject or obtained from a subject without a complement-related disorder, determining that the subject has or is likely to have a complement-related disorder (e.g. macular degeneration), and treating the subject with a therapeutic agent that reduces expression of one or more of FHR1-FHR5 (e.g., paras [0099]-[0114], [0199]-[0202], [0271]-[0275], [0286]-[0292], claims 1, 4, 6, 19, 22-24, 27, 29-31). Samples obtained from the subject are derived from blood and liver (e.g., paras. [01111]-[0115], claims 13, 14, 23, 29). Elevated levels of one or more proteins compared to a control subject are indicative of macular degeneration (e.g., [0189]-[0191], [0199]-[0202], [0272], claims 19, 22, 27, and 31). Bishop teaches that a complement-targeted therapeutic for use in the methods provided herein comprises a polypeptide which is capable of binding C3b, e.g. comprising an amino acid sequence having at least 85% identity to SEQ ID NO:146. SEQ ID NO:146 of Bishop has 100% sequence identity with instant SEQ ID NO:146 (e.g., [0263]). The therapeutic agent can reduce expression of one or more of FHR1-FHR5 (claims 27, 31).
Regarding claims 28 and 37, disclose macular degeneration, age related macular degeneration (AMD), geographic atrophy ('dry' (i.e. non-exudative) AMD), early AMD, early onset macular degeneration (EOMD), intermediate AMD, late/advanced AMD, 'wet' (neovascular or exudative) AMD, choroidal neovascularization (CNV), retinal dystrophy (paras. [0052], [200]-[202], claims 24 and 30).
Regarding claims 30 and 43, Bishop teaches that the level of the one or more proteins is determined by mass spectrometry (e.g., paras. [0018]-[0021], [0096]-[0098], [0018]-[0119], [0170]-[0186], [0209]-[0225], Exs 1-2, claims 1, 19, and 22).
Regarding claims 31 and 44, Bishop teaches a) digesting at least one complement protein in a sample obtained from the subject with endoproteinase GluC to obtain one or more peptides; b) determining the presence and/or level of the one or more peptides by mass spectrometry; and c) using the results of (b) to determine the likelihood of the subject to develop a complement-related disorder (e.g., paras [0030-[0050], [0137], [0199]-[0202], [0231]-[0234], [0256], [0270]-[0281], claims 1, 19, 22, 27, 31).
Regarding claims 32 and 39, Bishop teaches determining the level of two or more complement proteins, e.g. FHR1-5 (e.g., paras. [0024], [0111], [0124]-[0126], [0131]-[0137], [0232]).
Regarding 33 and 40, Bishop teaches determining the level of FHR4 (e.g. paras. [0084], [0124]-[0126], [0197], claims 6, 19, 22, 27, 31, 39, and 40).
Regarding claims 34 and 41, Bishop teaches determining the level of FH and/or FHL-1 (e.g., paras [0024], [0054], [0124]-[0125] [0131]-[0132], [0137], [0196], [0271]-[0274], claims 6, 19, 22).
Regarding claims 35 and 42, Bishop teaches determining the level of various combinations of FH, FHL-1, FHR1, FHR2, FHR3, FHR4 and/or FHR5 (e.g., paras. [0024], [0027], [0054]-[0055], [0111], [0124]-[0126], [0130]-[0137]).
Claim Rejections - 35 USC § 103
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.
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.
Please refer to the USPTO sequence interpretation section above relating “an amino acid sequence”.
Claim 27, 28, 32-37, and 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Her et al (US 2015/0079084 – cited in IDS filed 3/15/2023), and further in view of Zhang et al (Proteomics 17(6):10- cited in IDS filed 3/15/2023), Ansari et al (Human Mol Gene 22:4857-4869 (2013)- cited in IDS filed 3/15/2023), and Cipriani et al (ARVO mtg abstract (2019)- cited in IDS filed 3/15/2023).
Her et al teach a method of treating a subject with an ocular disease [0018, 0153] and useful to treat macular degeneration such as AMD [0155], [0052], by administering the polypeptide comprising the SEQ ID NO:5 (192 amino acids; the SCR8-10 of Complement Receptor Type 1 (CR1)), which has at least 85% identity to applicants elected SEQ ID NO:146 (194 amino acids). Specifically, amino acids 1-192 Her et al SEQ ID NO:5 100% identity with amino acids 2-193 of SEQ ID NO:146. Her et al teach at para [0155]:
[H]igh levels of complement proteins have been detected in drusen. Furthermore, genetic studies have confirmed association of AMD risk and polymorphism in genes of complement proteins including Factor H (CFH), CFHR1, CFHR3, C2, C3, Factor B, Factor I. In particular, the CFH Y402H allele correlates highly with AMD risk. Finally, increased levels of complement activation products have also been found in plasma of AMD patients. AMD can be detected in subjects with a visual acuity test, a dilated eye exam, an amsler grid, a fluorescein angiogram, or by genetic testing for AMD associated biomarkers.
Although Her et al teach administering a polypeptide of SEQ ID NO:5 to treat a macular degeneration, and discloses that high levels of complement proteins were known to be associated with macular degeneration, the reference does not explicitly teach a step of determining the level of a recited complement factor to assess whether a subject has or is likely to develop a macular degeneration.
Zhang et al teach that two variants in the complement factor H (CFH) gene, Y402H and I62V, are strongly associated with risk of AMD. CFH is encoded in Regulator of Complement Activation gene cluster in chromosome 1q32, which includes complement factor-related (CFHR) proteins, CFHR1 to CFHR5, with high amino acid sequence homology to CFH. The goal was to build a selected reaction monitoring (SRM) assay to measure plasma concentrations [reads on blood sample] of CFH variants Y402, H402, I62, and V62, and CFHR1–5 (abstract). Zhang et al teach SRM assay should facilitate the study of the role of systemic complement and risk of AMD. Id. Specific peptides unique to each of CFH and CFHR1-5 are found in table 1.
Ansari et al teach that CFH and CFHR1 levels are elevated in blood samples from subjects with age-related macular degeneration (abstract, pp. 4860, 4864-65).
Cipriani et al teach FHR4 levels are elevated in patients with age-related macular degeneration, as compared to control.
It would been obvious to one of ordinary skill the art to assess the blood /plasma/serum levels of one or more of complement proteins e.g. FHR1, FHR2, FHR3, FHR5, FHR4, FHL-1 and/or FH as compared to a control subject not having macular degeneration, to determine if a subject is at risk or is likely to develop a macular degeneration. As taught by Her et al, the skilled artisan would have known that high levels of complement proteins were known to be associated with macular degeneration. Ansari and Cipriani further confirmed that the denoted complement proteins are elevated in subjects with age-related macular degeneration. The skilled artisan would further have known that Zhang et al taught a method using mass spectrometry to assess complement protein levels, particularly with reference to subjects with age-related macular degeneration. Zhang taught use of the assay for risk stratification and/or therapeutic intervention (p. 7). Her et al taught methods of treating a macular degeneration, including administering to a subject a polypeptide having 100% identity with instant SEQ ID NO:146 to treat the macular degeneration.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual sequences and their use in treating complement-related diseases or conditions, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success. The motivation to combine the teachings can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07.
Accordingly, claims 27 and 36 are rendered obvious.
Regarding claims 28 and 37, Her et al teach that the macular degeneration include but are not limited to wet age-related macular degeneration, dry age-related macular degeneration, wet AMD, and autoimmune uveitis.
Regarding claims 30, 31, 43 and 44, Zhang et al disclose the use of enzymatic digestion of a blood sample obtained from a subject, performing mass spectrometry, and assessing the levels of specific peptides to determine if a complement protein is elevated. See Zhang for methodology and peptides.
Regarding claims 32-35 and 39-42, the references taught that high levels of complement proteins were known to be associated with macular degeneration. Ansari and Cipriani further confirmed that recited complement proteins are elevated in subjects with age-related macular degeneration. The skilled artisan would further have known that Zhang et al taught a method using mass spectrometry to assess complement protein levels, particularly with reference to subjects with age-related macular degeneration. It would have been a matter of routine optimization on the part of the skilled artisan to assess various combinations of the claimed complement proteins. The art taught measurement of the claimed protein(s), from the blood sample and that an elevated level as compared to control sample was indicative of a complement related disorder, e.g., AMD. Accordingly, claims 32-35 and 39-40 are rendered obvious.
Claims 27, 28, 32-37, and 39-40 are rendered obvious in view of the teachings of the cited references.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
**As noted under the Claim Objections section, instant claims 36-44 are substantial duplicates of instant claims 27-35. To avoid redundancy in the following ODP rejections, overlapping claims are identified together.
Claim 27, 28, 32-37, and 39-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 20, 24 and 25 of copending Application No. 18519153 (hereinafter referred to as “the ‘153 application”). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 27 and 36, claims 20, 24 and 25 of the ‘153 application disclosed method of treating or preventing a complement related disorder (e.g., age related macular degeneration, geographic atrophy, retinal dystrophy) in a subject comprising administering to the subject a therapeutically effective amount of the agent of according to claim 1. Claim 24 discloses that prior to administering the agent, the method comprises determining the level of a complement protein selected from the group of one or more of FHR1, FHR2, FHR3, FHR4 and/or FHR5, and optionally FHL-1 and a blood sample obtained from the subject in determining whether the level of the complement factor is elevated in comparison to the complement protein and employed in a subject that is not have the recited disorder. Claim 1 of the ‘153 application discloses an agent for reducing change and/or protein expression of one or more Factor H family proteins. Claim 2 of the ‘153 application discloses one or more Factor H family proteins are Factor H-related proteins, optionally wherein the Factor H-related proteins are selected from FHR1, FHR2, FHR3, FHR4 and FHR5.
Regarding claims 28 and 37, claim 25 of the ‘153 application discloses macular degeneration, age related macular degeneration (AMD), geographic atrophy ('dry' (i.e. non-exudative) AMD), early AMD, early onset macular degeneration (EOMD), intermediate AMD, late/advanced AMD, 'wet' (neovascular or exudative) AMD, choroidal neovascularisation (CNV), retinal dystrophy.
Regarding claims 32-35 and 39-42, claim 2 of the ‘153 application discloses the determining the level of the complement protein selected from FHR1, FHR2, FHR3, FHR4 and/or FHR5, and optionally FHL-1. It would have been a matter of routine optimization on the part of the skilled artisan to assess various combinations of the claimed complement proteins. The claims of the ‘153 application expressly taught measurement of the claimed protein, from the claimed blood sample and that an elevated level as compared to control sample was indicative of a complement related disorder. Accordingly, claims 32-35 and 39-40 are rendered obvious.
Claims 27, 28, 30-37, and 39-44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 12-14, 19, 22-24, and 27-42 of copending Application No. 18052795 (hereinafter referred to as “the ‘795 application”). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 27 and 36, claims 19, 22, 27, and 31 of the ‘795 application are drawn to a method of treating a complement related disorder in a subject, comprising digesting at least one complement protein in a sample obtained from the subject with Endo proteinase GluC the day one or more peptides, determining the presence and/or absence of the one or more peptides by mass spectrometry, using the results to determine whether the subject has an increase in the level of one or more of FHR1, FHR2, FHR3, FHR4 and/or FHR5; as compared to a control from a subject without a complement related disorder; and treating the subject with a therapeutically effective amount of a complement targeted therapeutic. Claims 23 and 29 of the ‘795 application recites that the sample comprises or is derived from blood or tissue from the subject. Claim 27 of the ‘795 application recites that the therapeutic is an agent that reduces the level of the one or more of FHR1, FHR2, FHR3, FHR4 and/or FHR5.
Regarding claims 28 and 37, claim 24 and 30 of the ‘795 application disclose macular degeneration, age related macular degeneration (AMD), geographic atrophy ('dry' (i.e. non-exudative) AMD), early AMD, early onset macular degeneration (EOMD), intermediate AMD, late/advanced AMD, 'wet' (neovascular or exudative) AMD, choroidal neovascularisation (CNV), retinal dystrophy.
Regarding claims 30, 31, 43, and 44, claims 1, 19, 22, 27, and 31 of the ‘795 application discloses enzymatic digestion of the complement protein in the sample comprising endoproteinase GluC, obtaining one or more peptides thereof, performing mass spectrometry to assess the peptide level, and using the results to determine if the level of a complement protein is elevated/increased.
Regarding claims 32 and 39, claims 1, 4, 35, and 37 of the ‘795 application recite identifying the level of 2 or more complement proteins, e.g. FHR1-5.
Regarding 33 and 40, claims 6, 19, 22, 27, 31, 39, and 40of the ‘795 application recite determining the level of FHR4.
Regarding claims 34 and 41, claims claim 38 of the ‘795 application recites further comprises FH and/or FHL-1..
Regarding claims 35 and 42, claims 1, 4, 6, 19, 22, 27, 31, 37-41 of the ‘795 application discloses the determining the level of the complement protein selected from FHR1, FHR2, FHR3, FHR4 and/or FHR5, and optionally FHL-1. It would have been a matter of routine optimization on the part of the skilled artisan to assess various combinations of the claimed complement proteins. The claims of the ‘795 application expressly taught measurement of the claimed proteins, from the claimed blood sample and that an elevated level as compared to control sample was indicative of a complement related disorder. Accordingly, claims 35 and 42 are rendered obvious.
Conclusion
No claims are allowed.
Claims 27-44 are pending. Claims 29 and 38 are withdrawn.
Claims 27, 28, 30-37, and 39-44 are rejected.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
Prosecution Insights