Patent Docs

Guest Post -- Patent Beauty: IP and the Cosmeceutical Industry

By Shin Hee Lee* and Anthony D. Sabatelli** --

The cosmeceutical industry is ever more competitive and continues to grow with a myriad of new cosmeceutical products entering the market every day.  Well-established and new companies are busily adapting to new trends created by people's changing tastes.  The total revenue of the U.S. cosmeceutical industry has only been increasing since 2009, marking $62.46 billion in 2016.  While this revenue comes from a number of cosmeceutical product categories, skin care has always been the most profitable category, covering 36% of the global market.  In this article, we discuss some of the recent growth and trends in skin care cosmeceutical patents.

It is often unknown that the 182 most recognized beauty brands in the world are actually owned by seven major cosmeceutical companies:  L'Oréal, Johnson and Johnson, Shiseido, Estée Lauder Companies, Unilever, Coty, and Procter & Gamble.  L'Oréal umbrellas the most brands with a total of 39 prevalent companies in an array of beauty stores.  These store brands are very well-known, including Kiehl's, Lancôme, The Body Shop, Urban Decay, and Maybelline.  On the other hand, the Estée Lauder Companies own internationally recognized luxury brands such as Clinique, Bobbi Brown, MAC, Jo Malone, Lab Series, and Glamglow.  These brands highly occupy the shelves in Sephora and other popular beauty vendors.  The plethora of products and the explosion of marketing venues suggests how competitive it can be for new cosmeceutical companies to succeed in the market.

To be competitive in the cosmeceutical industry, a company, whether new, rising or established, should focus on establishing solid intellectual property (IP) rights.  IP rights protect and support elements that help companies distinguish their products from rival companies.  Furthermore, the number of patents can be a powerful marketing tool, especially when touting the "patented" technology used to develop the product.

Because of the significance of IP rights in the cosmeceutical industry, there is currently an overwhelming number of cosmeceutical patents.  Skin care has the leading number of patents, correlating to its enormous global sales (projected to reach $130 billion by 2019).

Anti-aging has been the most popular category within skin care, attributed to the high demand of products promoting youthful looks that defy a consumer's biological age.  The majority of anti-aging patents relate to inventions based on unique compositions of known or novel ingredients.  An assortment of vitamins like retinol (made from vitamin A), vitamin C, coenzyme Q-10, and alpha-hydroxy acids (AHAs) have traditionally been touted to have anti-aging efficacies.  However, with the recent beauty trend of "clean cosmeceuticals," some patentees have pointed at the toxicity of some complementary additives in these vitamins and have filed patents for supposedly more natural plant-based components.  Some anti-aging products contain peptides instead of vitamins as their main component.  A recent study has shown that defensins, a group of antimicrobial peptides that activate stem cells to produce new skin, provide incredible anti-aging effects.  Many reporters have been labeling defensins as "a game changer," and "the newest anti-aging weapon."  Patents on anti-aging formulations will likely surface in the near future.

Another area of intense patent activity relates to cosmetic devices.  Portable home skin care devices for measuring and improving skin conditions have been increasingly patented and commercialized.  One of the pioneers that popularized hand-held devices was a company named Clarisonic (or Pacific Biosciences Laboratories), which owns 40 patents on their devices.  Clarisonic's iconic cleansing tool is a mechanically rotating face brush that oscillates back and forth over the skin to thoroughly remove any oil, debris, makeup and environmental pollutants.  Recently, Neutrogena has introduced small portable stick that treats acne using phototherapy.  Depending on the light color, the stick can treat different types of skin problems.  One futuristic skin care device on the rise is a mirror with built-in digital sensors that detect and analyze the skin's moisture, oiliness, and redness.  Devices that were only accessible at a dermatologist's office are increasingly becoming home-friendly.  We expect the skin care device patents continue to increase in the coming years, especially the design patents.

Shown below are two tables summarizing some of the patent trends for cosmetics and recent devices.

* Shin Hee Lee is a Ph.D. Candidate in the Chemistry Department at Yale University.  She is currently associated with the Yale Energy Sciences Institute, where she specializes in organic synthesis of novel light-harvesting dye molecules for solar cells.  Prior to attending Yale, Shin Hee obtained her B.S. in Chemistry with High Honors at the University of Michigan – Ann Arbor, during which she published patents and papers on developing synthetic methodologies for fluorinated small molecules.
** Dr. Sabatelli is a Partner with Dilworth IP

Patent Profile: DermTech Receives Patent for Method of Detecting Melanoma in Human Subjects

By Josh Bosman --

The U.S. Patent and Trademark Office recently issued a notice of allowance for U.S. Application No. 14/199,900, which is entitled "Diagnosis of Solar Lentigo by Nucleic Acid Analysis."  The '900 application, which is assigned to the DermTech International, contains claims to a method of detecting melanoma in a human subject.  DermTech is a San Diego-based biotechnology company developing and commercializing gene expression tests to facilitate the diagnosis of dermatologic conditions.

Melanoma is the most serious type of skin cancer, but can be treated successfully if it is detected early.  Most melanoma deaths can be prevented by surgical excision if they are detected in their early stages.  The methods of the '900 application help to enable physicians to determine the nature and extent of suspicious lesions of the skin by providing accurate, objective information to the physicians to improve care while reducing costs.  More specifically, DermTech's technology allows the analysis of skin samples collected non-invasively using an adhesive patch.

The '900 application has two independent claims which recite:

Claim 1.    A method of detecting melanoma in a human subject comprising:
    (a) obtaining a sample of a skin lesion suspected of comprising melanoma from a human subject, wherein the skin lesion sample comprises or is suspected of comprising a nucleic acid molecule expressed from C6orf218;
    (b) detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample, whereby the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample in an amount that is greater than the presence of C6orf218 in a non-melanoma sample is indicative of melanoma in the skin lesion sample, wherein detecting the presence of a nucleic acid molecule expressed from C6orf218 is by application of a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218; and
    (c) characterizing the skin lesion as having melanoma or not having.

Claim 15.    A method for diagnosing melanoma in a subject, comprising:
    (a) obtaining a sample of a skin lesion suspected of comprising melanoma from a subject, wherein the skin lesion sample comprises or is suspected of comprising a nucleic acid molecule expressed from C6orf218;
    (b) detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample, wherein detecting the presence of a nucleic acid molecule expressed fromC6orf218 is by application of a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218; and
    (c) comparing the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample to the presence of C6orf218 in a non-melanoma sample, whereby the increased presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample as compared to the non-melanoma sample is indicative of melanoma, thereby diagnosing the skin lesion as having melanoma.

A review of the file history of the `900 application (examined under Track I) indicates a rejection under 35 U.S.C. § 101 was issued (along with rejections under §§ 112, 102, and 103) in the first Office Action, mailed December 10, 2014.  The Action stated that the claimed invention was directed to patent ineligible subject matter.  Specifically, the Action asserted that the claims were directed to a natural correlation or a natural principle (i.e., the claims reflect the natural correspondence between gene expression and melanoma).  Furthermore, the Action asserted that the claimed methods failed to incorporate steps that amount to significantly more than the natural principles themselves because the steps merely incorporate conventional, routine techniques while failing to incorporate some other inventive concept.

In response, with respect to the 101 rejection, the Applicant argued that the claims, as amended, are patent eligible because the amended claims do not seek to tie up the use of C6orf218, and others are not excluded from using C6orf218 or C6orf218 expression products in other ways that do not utilize the claimed methods for detecting or diagnosing melanoma.  Furthermore, the Applicant argued that the claims as amended are not directed to a judicial exception because the claims are directed to methods of using "a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218" and to determine the presence of C6orf218 for "detecting melanoma in a human subject" or for "diagnosing melanoma in a subject".

Finally, the Applicant argued that the amended claims recite an inventive concept because claims 1 and 15, provide methods for "detecting melanoma in a human subject" or for "diagnosing melanoma in a subject," by "detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample," which, according to the Applicant, is not taught, alone or in combination, by the art cited in the Action.

Claims 1 and 15 as amended recited:

Claim 1.    A method of detecting distinguishing melanoma from dysplastic nevi or normal pigmented skin in a human subject comprising:
    (a) obtaining a sample of a skin lesion suspected of comprising melanoma from a human subject, wherein the skin lesion sample comprises or is suspected of comprising a nucleic acid molecule expressed from C6orf218;
    (b) detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample, whereby the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample in an amount that is greater than the presence of C6orf218 in a non-melanoma sample is indicative of melanoma in the skin lesion sample, wherein detecting the presence of a nucleic acid molecule expressed from C6orf218 is by application of a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218analyzing expression of a nucleic acid molecule encoded by C6orf218; and
    (c) characterizing the skin lesion as having being melanoma or not having ,dysplastic nevi, or normal pigmented skin, thereby distinguishing melanoma from dysplastic nevi or normal pigmented skin in a human subject.

Claim 15.    A method for diagnosing melanoma in a subject, comprising:
    (a) obtaining a sample of a skin lesion suspected of comprising melanoma from a subject, wherein the skin lesion sample comprises or is suspected of comprising a nucleic acid molecule expressed from C6orf218;
    (b) detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample, wherein detecting the presence of a nucleic acid molecule expressed fromC6orf218 is by application of a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218; and
    (c) comparing the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample to the presence of C6orf218 in a non-melanoma sample, whereby the increased presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample as compared to the non-melanoma sample is indicative of melanoma, thereby diagnosising the skin lesion as having melanoma providing a gene expression profile of a target area suspected of being melanoma on the skin of the subject; and
(b) analyzing the subject's gene expression profile with respect to a reference gene expression profile obtained from a corresponding normal skin sample, wherein the reference gene expression profile comprises an expression value of a target gene that is C6orf218.

The file history indicates that a search was performed by the Examiner following the Applicant's response, but the notice of allowance mailed on March 30, 2015 provides no additional comments concerning the allowability of the claims other than noting that the application is in condition for allowance.

Patent Profile: VM Institute of Research Receives Patent for Method of Treating Triple Negative Breast Cancer

By Josh Bosman --

The U.S. Patent and Trademark Office recently issued U.S. Patent No. 8,642,270, which is entitled "Prognostic biomarkers to predict overall survival and metastatic disease in patients with triple negative breast cancer."  The '270 patent, which is assigned to the VM Institute of Research (Montreal, Canada), contains claims to a method of treating breast cancer in a subject having triple negative breast cancer.

For some time doctors and scientists hypothesized that the diversity observed among breast tumors might be accompanied by diversity in gene expression patterns.  Over ten years ago, Perou and colleagues published their work on the "Molecular portraits of human breast tumours" (Perou et al., 2000 Nature 406: 747-52) classifying human breast tumors based their gene expression profiles.  This work was soon followed up with studies that linked the gene expression profiles of each breast cancer subtype with patient overall survival and disease free survival.  One of the subtypes identified was the basal-like subtype.  The basal-like subtype is also described as triple-negative breast cancer because it generally does not express estrogen receptor (ER), progesterone receptor (PR), and expresses only normal, but not amplified, levels of the human epidermal growth factor receptor 2 (HER2).  Given the nature of the triple-negative breast tumors, this subtype does not respond to cancer drugs that target ER, PR or HER2 (i.e., Taxol® or Herceptin®), and has poorer overall survival and disease-free survival than other breast cancer subtypes.  The triple negative paradox (Carey et al., 2007 Clin Cancer Res. 13(8): 2329-34) is that these tumors often respond well to the initial chemotherapy treatments, and yet patients have significantly poorer overall survival.  The work by the inventors of the `270 patent helps to develop effective methods to determine whether a triple negative breast cancer patient is likely to have a recurrence or progress to the aggressive, metastatic disease in order to aid clinicians in deciding the appropriate course of treatment.

The '270 patent provides a method of treating breast cancer in a subject having a triple negative breast cancer.  The inventors were able to identify a 12 gene set that correlates with overall survival of the triple negative breast tumors.  More specifically, the inventors determined that the expression of STK3, KLF6, CD24 and KRAS, could be indicative of a recurrent triple negative breast tumor.

The '270 patent has one independent claim which recites:

1.  A method of treating breast cancer in a subject having a triple negative (TN) breast cancer, the method consisting of the steps:
    (a)  quantifying mRNA expression level of biomarkers STK3 and KLF6, and at least one biomarker selected from CD24 and KRAS in a test sample from a subject using a biological assay;
    (b)  comparing said mRNA expression level of said biomarkers selected from STK3, KLF6, and at least one of CD24 and KRAS quantified in step (a) to the expression level of said biomarkers quantified using the biological assay in a standard sample indicative of a recurrent TN breast cancer; and
    (c)  administering an aggressive cancer treatment regimen to the subject based on an increase in the expression level of the biomarkers between the standard sample and the test sample.

A review of the file history of the '270 patent indicates that a rejection under 35 U.S.C. § 101 rejection was issued in the first Office Action.  The Action stated that the claimed invention is directed to non-statutory subject matter because it is not a patent-eligible practical application of a law of nature and because the claimed method does not result in a physical transformation of matter.  Specifically, the Action asserted that the claims do not recite additional elements or steps such that the method is sufficient to ensure that the claim amounts to significantly more than the natural principle itself or merely more than mental tasks.

The original claim 1 as filed recited:

1. A method of predicting the overall survival (OS) potential of a triple negative (TN) breast cancer in a subject, the method comprising the step:
    (a)  comparing expression level of at least one biomarker determined in a test sample from a subject to the expression level of the at least one biomarker in a standard sample indicative of a recurrent TN breast cancer, wherein the at least one biomarker is chosen from ANK3, CD24, EIF1, KLF6, KRAS, KRT1, MAP2K4, SDC4, SLC2A3, STK3, TFAP2C, and WRN; and wherein a difference in the expression level of the at least one biomarker between the standard sample and the test sample is used to predict the OS potential of the TN breast cancer in the subject.

In response, the Applicant amended claim 1 to introduce an additional step of modifying a treatment regimen of the subject based on the results of step (a).  The Applicant asserted that with the new step, the method as amounted to "significantly more than the application of a natural principle."

Claim 1 as amended recited:

1.  (Currently Amended) A method of predicting the overall survival (OS) potential of a triple negative (TN) breast cancer in a subject, the method comprising the step:
    (a)  comparing a mRNA expression level of at least threeone biomarkers chosen from STK3, KLF6, and one of CD24 or KRAS determinedquantified using a biological assay in a test sample from a subject to the expression level of the at least threeone biomarkers quantified using the biological assay in a standard sample indicative of a recurrent TN breast cancer, wherein the at least one biomarker is chosen from ANK3, CD24, EIF1, KLF6, KRAS, KRT1, MAP2K4, SDC4, SLC2A3, STK3, TFAP2C, and WRN; and
    (b)  modifying a treatment regimen of the subject based on the results of step (a) wherein a difference in the expression level of the at least one biomarkers between the standard sample and the test sample is used to predict the OS potential of the TN breast cancer in the subject.

In the next and final Office Action mailed July 30, 2013, the Office maintained the rejection of the claims under 35 U.S.C. § 101 because the invention was not a patent-eligible practical application of a law of nature.  The Action noted that the claims recited methods steps for detecting or determining and comparing marker levels from samples, but asserted that these steps are routine or conventional, and do not add anything substantial to the claim that amounts to significantly more than observing the natural principle itself.  Regarding the step of "modifying a treatment regimen," the Action stated that such a step can be "accomplished mentally by thinking or designing a new treatment plan, and does not set forth any physical steps."

Furthermore, in the final Office Action, the Examiner suggested "amending the claims to recite an active step of administering a specified treatment regimen based on specific results (specific results such as increased or decreased mRNA levels of STK3, KLF6, and CD24 or KRAS relative to specific controls) to a patient population identified by such specific results."  Additionally, the Action stated that "prediction of survival rates as correlated to naturally occurring mRNA levels are considered an observation of a naturally occurring principle and an active step must be added to the claimed method that amounts to significantly more than the observation of the natural principle."

On September 17, 2013, in the response to the final Office Action, the Applicant stated "without conceding the correctness of the Examiner's position and for the purpose of expediting prosecution, Claim 1 has been amended to introduce an additional step (c), as suggested by the Examiner."  Claim 1 was amended claim 1 as shown below:

1.  (Currently Amended) A method of predicting the overall survival (OS) potential of a triple negative (TN) treating breast cancer in a subject having a triple negative (TN) breast cancer, the method comprisingconsisting of the steps:
    (a)  quantifying mRNA expression levels of biomarkers STK3 and KLF6, and at least one biomarker selected from CD24 and KRAS in a test sample from a subject using a biological assay;
    (b)  comparing [[a]]said mRNA expression level of at least three said biomarkers chosen selected from STK3, KLF6, and at least one of CD24 andor KRAS quantified in step (a) using a biological assay in a test sample from a subject to the expression level of said the at least three biomarkers quantified using the biological assay in a standard sample indicative of a recurrent TN breast cancer; and
    (c[[b]])  modifyingadministering an aggressive cancer treatment regimen ofto the subject based on the results of step (b[[a]]) wherein a difference an increase in the expression level of the biomarkers between the standard sample and the test sample is used to predict the OS potential of the TN breast cancer in the subject.

A notice of allowance was mailed on October 1, 2013.

Patent Profile: Patent Issued for Method of Differentiating Pancreatic Cancer from Benign Pancreatic Disease

By Josh Bosman --

The U.S. Patent and Trademark Office recently issued U.S. Patent No. 8,632,983, which is entitled "Biomarkers for pancreatic cancer and diagnostic methods."  The '983 patent, which is assigned to the Van Andel Research Institute and the University of Pittsburgh, contains claims to a method for differentiating pancreatic cancer from a benign pancreatic disease.

The invention provides a method for diagnosing pancreatic cancer; more specifically, a method for differentiating pancreatic cancer from a benign pancreatic disease in a patient having or suspected of having a pancreatic disease.  The invention could be particularly helpful in the early diagnosis of pancreatic cancer.  Pancreatic cancer is typically diagnosed at a more advanced stage, and treatment options are limited, leading to five year survival rates of less than 5%.  The inventors indicate that a blood-based diagnostic test for pancreatic cancer would be especially valuable, potentially increasing survival rates and saving resources.

The inventors used antibody arrays to measure the levels of a carbohydrate antigen, CA 19-9, on multiple proteins in 420 individual biological samples from patients with pancreatic adenocarcinoma or pancreatitis.  It is known that the CA 19-9 antigen is elevated in serum from the majority of pancreatic cancer patients, but using CA19-9 in diagnostic tests is discouraged in the guidelines from the American Society of Clinical Oncology due to both false positive and false negative readings.  Surprisingly, the inventors discovered that a subset of cancer patients showed elevations of the CA 19-9 antigen on the mucin proteins MUC1, MUC5AC, or MUC16.  By combining measurements of total CA 19-9 with CA 19-9 on the MUC1, MUC5AC, or MUC16 proteins, the inventors determined that they could differentiate, with sensitivity and specificity, whether the sample was from a patient with pancreatic cancer or a patient with a benign pancreatic disease.

The '983 patent has one independent claim which recites:

1.  A method for differentiating pancreatic cancer from a benign pancreatic disease, comprising the steps:
    obtaining a patient biological sample from a patient having or suspected of having a pancreatic disease;
    assaying the patient biological sample (a) to detect a total level of CA 19-9 antigen in the patient biological sample and (b) to detect a glycan level in MUC16 in the patient biological sample;
    comparing the total level of CA 19-9 antigen in the patient biological sample to a statistically validated threshold for total CA 19-9 antigen, which statistically validated threshold for total CA 19-9 antigen is based on a total level of CA 19-9 antigen in comparable control biological samples from patients having a benign pancreatic disease; and
    comparing the glycan level in the MUC16 in the patient biological sample to a statistically validated threshold for the MUC16, which statistically validated threshold for the MUC16 is based on a glycan level in the MUC16 in comparable control biological samples from patients having a benign pancreatic disease;
    wherein (a) a different level of total CA 19-9 antigen in the patient biological sample as compared to the statistically validated threshold for total CA 19-9 antigen and (b) a different level of glycan level in the MUC16 in the patient biological sample as compared to the statistically validated threshold for the MUC16 indicate that the patient has pancreatic cancer rather than a benign pancreatic disease.

A review of the file history of the '983 patent indicated that a rejection under 35 U.S.C. § 101 was not issued.

Patent Profile: National Tsing Hua University Receives Patent for Method for Early Diagnosis of Liver Cancer

By Josh Bosman --

Last week, the U.S. Patent and Trademark Office issued U.S. Patent No. 8,628,920, which is entitled "Method for early diagnosis of liver cancer and prediction of metastasis."  The '920 patent, which is assigned to National Tsing Hua University in Taiwan, contains claims to a method of determining the risk of liver cancer and metastasis.

The inventors demonstrated that alpha-mannosidase RNA expression levels, specifically MAN1A1, MAN1A2 and MAN1B1, in liver tissue obtained from hepatitis B virus positive liver cancer patients were approximately double the levels of control liver tissue, with increased RNA expression levels correlating with a more advanced cancer stage.  Interestingly, MAN1C1 RNA expression levels in stage I or II liver cancer patients were approximately half the level than that in normal liver tissue.

A review of the file history of the '920 patent indicates that the Examiner issued a rejection of the claims under 35 U.S.C. § 101 in a non-final Office Action mailed December 4, 2012 for being drawn to a non-statutory method for having a "natural princip[le]" as a limiting step without reciting additional steps that integrate the natural principle into the claimed invention.  The Examiner asserted that the natural principle constituted the levels of MAN1A1, MAN1A2, MAN1B1, MAN1C1, and MMP9 in samples from a subject as compared to controls are indicative of risk of liver metastasis.  The Examiner stated that, according to Mayo v. Prometheus, a claim that focuses on use of a natural principle must also include additional elements or steps to show that the inventors have practically applied, and added something significant, to the natural principal itself.

As originally filed, claim 6 of the '920 patent recited:

6.  A method for diagnosis of liver metastasis, comprising the steps of:
    (A)  providing a sample obtained from a subject;
    (B)  assessing the expression level of four subtypes of α-mannosidase genes consisting of MAN1A1, MAN1A2, MAN1B1 and MAN1C1 in the sample;
    (C)  comparing MAN1A1, MAN1A2, MAN1B1 and MAN1C1 expression level in the sample with those in a normal control; and
    (D)  determining whether the subject having a risk of liver metastasis in accordance with the result of step (C);
    wherein while the MAN1A1, MAN1A2 and MAN1B1 expression levels in the sample are higher than those in the normal control, and the MAN1C1 expression level in the sample is lower than that of the normal control, such that the subject is determined to have a risk of liver metastasis.

In response to the § 101 rejection, the Applicant amended claim 6 to add limitations of "specific markers" to detect and assess and compare the expression level by the "specific markers."  Furthermore, the Applicant asserted that claim 6 must be performed using the substantial "specific markers" and thus, the claim amounts to significantly more than a natural principle itself.

In Applicant's response filed on April 8, 2013, claim 6 was amended as follows:

6.  (Currently amended)  A method for diagnosis determining risk of liver metastasis metastatic liver cancer, comprising the steps of:
    (A)  providing a sample obtained from a subject;
    (B)  assessing the RNA expression level of four subtypes of α-mannosidase genes consisting of MAN1A1, MAN1A2, MAN1B1 and MAN1C1 in the sample by detecting with one or a plurality of specific markers;
    (C)  comparing the specific markers of MAN1A1, MAN1A2, MAN1B1 and MAN1C1 expression level in the sample with those in a normal control; and
    (D)  determining whether the subject having has a risk of liver metastasis of liver cancer in accordance with the result of step (C);
    wherein a subject with while the MAN1A1, MAN1A2 and MAN1B1 expression levels in the sample that are higher than those in the normal control, and [[the]] MAN1C1 expression level in the sample that is lower than that of the normal control, such that the subject is determined to have indicates the subject has a high risk of liver metastasis of liver cancer,
    wherein the sample and the normal control are liver biopsy or blood sample.

In the next and final Office Action mailed May 29, 2013, the Examiner withdrew the § 101 rejection without comment, but issued a rejection under 35 U.S.C. § 112, second paragraph, for the unclear recitation of "markers" in claim 6.  In order to expedite prosecution, the Examiner proposed amendments to claim 6 that removed the "specific markers" amendment made by the Applicant.  In a response to the final Office Action filed in August of 2013, the Applicant amended claim 6 (which issued as claim 1 in the '920 patent) to include the Examiner's recommended amendment to remove the recitation of "specific markers."  The application was allowed in September.

Claim 1 of the '920 patent recites:

Claim 1.  A method for determining risk of metastatic liver cancer, comprising the steps of:
    (A)  providing a sample obtained from a subject;
    (B)  assessing the RNA expression level of four subtypes of alpha-mannosidase genes consisting of MAN1A1, MAN1A2, MAN1B1 and MAN1C1 in the sample by detecting MAN1A1, MAN1A2, MAN1B1 and MAN1C1 RNA expression levels in the sample;
    (C)  comparing the MAN1A1, MAN1A2, MAN1B1 and MAN1C1 expression levels in the sample with MAN1A1, MAN1A2, MAN1B1 and MAN1C1 expression levels in a normal control; and
    (D)  determining whether the subject has a risk of metastasis of liver cancer in accordance with the result of step (C);
    wherein a subject with MAN1A1, MAN1A2 and MAN1B1 expression levels in the sample that are higher than those in the normal control, and MAN1C1 expression level in the sample that is lower than that of the normal control has a high risk of metastasis of liver cancer, wherein the sample and the normal control are liver biopsies.

Patent Profile: Duke University and Cognosci Receive Patent for Methods of Diagnosing Cancer

By Josh Bosman --

Last week, the U.S. Patent and Trademark Office issued U.S. Patent No. 8,623,601, which is entitled "Methods of diagnosing cancer."  The '601 patent, which is assigned to Duke University and Cognosci, Inc. (out of the Research Triangle Park in North Carolina), contains claims to a method of predicting or assessing the level of severity of cancer or cancer progression in a patient diagnosed with chronic lymphocytic leukemia or B-cell non-Hodgkin's lymphoma.

The claimed method is based on the discovery that the levels of SET present in a biological sample and the ratio of SET protein isoforms SET α and SET β in the biological sample can be measured and are prognostic indicators of cancer severity or progression.  More specifically, the claimed method relies on measuring the levels of SET α and SET β protein or RNA in B lymphocytes isolated from a blood sample of a patient diagnosed with chronic lymphocytic leukemia or B-cell non-Hodgkin's lymphoma where the inventor learned that CLL patients with high α/β ratios had significantly shorter overall survival (~4 years shorter) than did patients with low α/β ratios.

The SET protein is a multitasking protein, involved in apoptosis, transcription, nucleosome assembly, and histone chaperoning, and is known to be a potent physiological inhibitor of protein phosphatase 2A.  The expression of the α and β isoforms is driven by distinct promoters, and the isoforms differ only in the N-terminal portion of the protein in which the α-isoform has a 37 amino acid N-terminal region that arises from Exon 1 of the SET gene while the β-isoform has a 24 amino acid N-terminal region that arises from Exon 2 of the SET gene.  As the SET protein was isolated from a chromosomal rearrangement at 9q34 in a patient with acute undifferentiated leukemia, it makes sense that it can now be used in methods to predict the level of severity of some types of leukemia.

The patent has one independent claim that recites:

1.  A method of predicting or assessing the level of severity of cancer or cancer progression in a patient diagnosed with chronic lymphocytic leukemia or B-cell non-Hodgkin's lymphoma comprising determining the ratio of SET alpha isoform to SET beta isoform in B lymphocytes isolated from the patient and  comparing the ratio of SET alpha isoform to SET beta isoform to the ratio in a control sample or a standard value, wherein an increase in the ratio of SET alpha isoform to SET beta isoform relative to the ratio in the control sample or standard value is indicative of a more severe form of cancer or later stage of cancer progression in the patient.

As cancer is predicted to overtake heart disease as the leading cause of death, there is a continued need for advancing methods for predicting the severity of cancers.  The '601 patent provides a method that would allow physicians to determine whether a particular leukemia patient would benefit from aggressive treatment or whether a less aggressive form of treatment is appropriate, which could improve the treatment strategy for the leukemia patient and may improve survival.

Bioethicists "Urge Maximal Transparency" in Response to 23andMe Patent

By Donald Zuhn --

Last week, we discussed a patent, recently issued to 23andMe, Inc., that has created some controversy.  The patent, U.S. Patent No. 8,543,339, is directed to a system for identifying a preferred gamete donor from among the plurality of donors based on a phenotype of interest, the genotype of a recipient, and the genotypes of the donors.  According to the '339 patent, one embodiment of the invention is disclosed in Figure 4 (below), which shows "a user interface for making [a] user specification and displaying the results," in which "the recipient has specified that she prefers low risk of colorectal cancer and congenital heart defects equally, and to a lesser degree she also prefers green eye color."

In the wake of the '339 patent's issuance, 23andMe has been criticized for its efforts to secure patent protection on a method of creating "designer babies."  A commentary regarding the "controversial patent" appeared in the journal Genetics in Medicine earlier this month (Sterckx et al., "I prefer a child with . . .": designer babies, another controversial patent in the arena of direct-to-consumer genomics," Genetics in Medicine (October 3, 2013)).  The article, authored in part by several bio- or medical ethicists and a patent attorney, notes that when "[t]aken out of 'patentese,' what 23andMe is claiming [in the '339 patent] is a method by which prospective donors of ova and/or sperm may be selected so as to increase the likelihood of producing a human baby with characteristics desired by the prospective parents."  The article focuses on two figures from the patent -- Figures 4 and 6 -- and particularly points to the alternative choices presented in Figure 4 (above) after the phrase "I prefer a child with:".

The article initially calls into question the U.S. examination process, noting that "at no stage during the examination of the patent application did the patent office Examiner question whether techniques for facilitating the 'design' of future human babies were appropriate subject matter for a patent."  However, the authors then acknowledge that "[i]t might be argued that this is not surprising [because] unlike the patent law operating across Europe (the European Patent Convention, or EPC), US patent law contains no explicit clause excluding from patent-eligibility inventions that contravene morality."  Then again, the authors suggest that "the utility requirement of US patent law includes a morality aspect which, admittedly, is very rarely applied by the US Patent and Trademark Office," and point out this aspect of the utility requirement was invoked when the Office rejected an application directed to human/animal chimeras that was filed by Stuart Newman and Jeremy Rifkin in 1997.

According to the authors, "it is clear that selecting children in ways such as those patented by 23andMe is hugely ethically controversial."  While the authors concede that "[t]he use of preimplantation genetic diagnosis to avoid implantation of embryos bearing serious genetic abnormalities is by now becoming commonplace," they argue that the use of "a computerized process for selecting gamete donors to achieve a baby with a 'phenotype of interest' that the prospective parent 'desires in his/her hypothetical offspring,' as 23andMe puts it, seems to have much broader implications."

The article concludes by stating that 23andMe's pursuit of the '339 patent, following the "uproar" that greeted the company's announcement in 2012 that it had been granted a patent on a test for determining the propensity to develop Parkinson disease, was "surprising."  In particular, the authors wonder why 23andMe, following its past experience, would have pursued the '339 patent "with no apparent public discussion."  Noting that "[p]ublic trust is central to the continuing success of human genetics research in general and biobank-based research in particular," the authors "urge maximal transparency by all engaged in human genetics research."

23andMe Patent Creates Controversy

By Donald Zuhn --

A patent issued to 23andMe, Inc. last month has created some controversy, and in response, the biotech company, based in Mountain View, California, has posted its side of the story on the 23andMe blog.  The patent, U.S. Patent No. 8,543,339, which is entitled "Gamete donor selection based on genetic calculations," is directed to a system for identifying a preferred gamete donor from among the plurality of donors based on a phenotype of interest, the genotype of a recipient, and the genotypes of the donors.  The patent contains three independent claims, which recite a system, method, and non-transitory computer program product for gamete donor selection:

1.  A system for gamete donor selection comprising:
one or more processors configured to:
    receive a specification including a phenotype of interest that can be present in a hypothetical offspring;
    receive a genotype of a recipient and a plurality of genotypes of a respective plurality of donors;
determine statistical information including probabilities of observing the phenotype of interest resulting from different combinations of the genotype of the recipient and genotypes of the plurality of donors; and
    identify a preferred donor among the plurality of donors, based at least in part on an evaluation of the statistical information determined, including:
        to compare the probabilities of observing the phenotype of interest resulting from different combinations of the genotype of the recipient and the genotypes of the plurality of donors to identify the preferred donor; and
a memory coupled to the processor, configured to provide the processor with instructions.

11.  A method for gamete donor selection, comprising:
    receiving a specification including a phenotype of interest that can be present in a hypothetical offspring;
    receiving a genotype of a recipient and a plurality of genotypes of a respective plurality of donors;
    using one or more computer processors coupled to one or more memories configured to provide the one or more computer processors with instructions to determine statistical information including probabilities of observing the phenotype of interest resulting from different combinations of the genotype of the recipient and genotypes of the plurality of donors; and
identifying a preferred donor among the plurality of donors, based at least in part on the statistical information determined, including:
        comparing the probabilities of observing the phenotype of interest resulting from different combinations of the genotype of the recipient and the genotypes of the plurality of donors to identify the preferred donor.

21.  A non-transitory computer program product for gamete donor selection, the computer program product being embodied in a computer readable storage medium and comprising computer instructions for:
    receiving a specification including a phenotype of interest that can be present in a hypothetical offspring;
    receiving a genotype of a recipient and a plurality of genotypes of a respective plurality of donors;
    determining statistical information including probabilities of observing the phenotype of interest resulting from different combinations of the genotype of the recipient and genotypes of the plurality of donors; and
    identifying a preferred donor among the plurality of donors, based at least in part on an evaluation of the statistical information determined, including:
        comparing the probabilities of observing the phenotype of interest resulting from different combinations of the genotype of the recipient and the genotypes of the plurality of donors to identify the preferred donor.

The detailed description of the '339 patent states that:

The gamete donors and gamete recipient's genetic information such as genome sequences and/or marker information is obtained and stored.  In some embodiments, the recipient is allowed to make a specification of one or more phenotypes of interest in the hypothetical offspring.  Statistical information pertaining to the likelihood of observing phenotypes of interest are determined, based on the genotype of the recipient and the genotypes of different donors.  For example, probabilities of the phenotypes of interest in the hypothetical offspring resulting from different recipient-donor combinations are computed.  Based on the statistical information, one or more preferred donors are identified and optionally selected by the recipient.

According to the '339 patent, one embodiment of the invention is disclosed in Figure 4 (below), which shows "a user interface for making [a] user specification and displaying the results," in which "the recipient has specified that she prefers low risk of colorectal cancer and congenital heart defects equally, and to a lesser degree she also prefers green eye color."  The '339 patent discloses that based on the user specification, a donor selection process is performed, and "the results page shows preferred donors A, B, and C, [wherein] the statistical distributions of the desired genotypes of the hypothetical child resulting from the combinations of the recipient and the donor, as well as an optional score calculated based on the statistical distribution are displayed."

In the wake of the '339 patent's issuance, 23andMe has been criticized for its efforts to secure patent protection on a method of creating "designer babies."  A commentary regarding the "controversial patent" appeared in the journal Genetics in Medicine last week (Sterckx et al., "I prefer a child with . . .": designer babies, another controversial patent in the arena of direct-to-consumer genomics," Genetics in Medicine (October 3, 2013)).

Possibly anticipating a backlash (the Genetics in Medicine commentary was submitted for publication two weeks before the '339 patent issued), 23andMe posted an article on its blog one week after the patent issued.  The article, entitled "A 23andMe Patent," notes that the company had "applied [for the patent] more than five years ago," and that the patent relates to one of the tools 23andMe offers to individuals "as part of their genetic exploration."  The article points out that:

The tool -- Family Traits Inheritance Calculator -- offers an engaging way for you and your partner to see what kind of traits your child might inherit from you.  The Family Trait Inheritance Calculator has also been part of our service since 2009 and is used by our customers as a fun way to look at such things as what eye color their child might have or if their child will be able to perceive bitter taste or be lactose intolerant.

The article indicates that "[w]hen 23andMe applied for the patent (#8543339) it was meant to cover the technology that supports our Family Traits Inheritance Calculator," but acknowledges that "the language of the patent extends beyond the calculator and so we want to be very clear about our technology and our intentions."  In particular, the article explains that:

At the time 23andMe filed the ['339] patent, there was consideration that the technology could have potential applications for fertility clinics so language specific to the fertility treatment process was included in the patent.  But much has evolved in that time, including 23andMe’s strategic focus.  The company never pursued the concepts discussed in the patent beyond our Family Traits Inheritance Calculator, nor do we have any plans to do so.

The Genetics in Medicine commentary will be discussed in a subsequent post.

Patent Profile: Mayo Foundation Receives Patent for Methods of Selecting Medications

By Josh Bosman --

In March, the U.S. Patent and Trademark Office issued U.S. Patent No. 8,401,801, entitled "Methods for Selecting Medications."  The '801 patent, which is assigned to the Mayo Foundation for Medical Education and Research, contains claims that share some similarities with the claims in U.S. Patent No. 6,680,302, which was licensed to Prometheus Laboratories, Inc., and which was at issue in Mayo Collaborative Services v. Prometheus Laboratories, Inc.

The claimed methods of the '801 patent include obtaining a biological sample from a patient and determining the patient's genotype for a panel of genes.  Then, based on the genotype for the panel of genes, a clinician would select a psychotropic medication for the patient, which according to the patent, provides a safe method to avoid potentially dangerous side effects.  The genes of interest in the '801 patent include at least three cytochrome P450 genes and a serotonin transporter gene.  These genes are known to be important for drug metabolism and neurotransmission, respectively, and when examined individually or collectively, may be correlated to a patient's sensitivity or resistance to a given medication.

A specific example of a gene of interest in the patent is the P450 CYP2D6, a gene with many known alleles corresponding to increased or decreased drug metabolizing activity.  For example, the CYP2D6*4 allele results in a truncated version of the gene's protein that does not have catalytic activity.  Therefore, a patient with the CYP2D6*4 allele would be determined to be a poor metabolizer and assigned to an appropriate medication profile that provides medications that are acceptable for use or medications to be used with caution under close monitoring.  By determining a patient's genotype for the panel of genes claimed, a practitioner can use the methods of the invention to anticipate side effects to a medication and allow a clinician to avoid a number of medications a patient may not tolerate.

The two independent method claims recite a long list of genes and alleles to be examined in step (1) and an even longer list of medications to select from based on the patient's genotype in step (3).  Abridged versions of claims 1 and 2 recite (with emphasis added):

1.  A method of administering an antidepressant medication to a patient in need thereof comprising:
    (1)  determining the patient[']s genotype for a panel of genes comprising the following: . . .
    (2)  assigning a metabolic phenotype to the patient based on the genotype of the cytochrome P450 genes in (1), wherein the metabolic phenotype is selected from poor (P), intermediate (I), and extensive (E), and said phenotype is assigned based upon the number of functional alleles for each cytochrome P450 gene as follows: P=no fully functional alleles and either one or no partially functional alleles, I=either one fully functional allele and a non-functional allele or two partially functional alleles, and E=either one fully functional allele and one partially functional allele or two fully functional alleles; and
    (3)  administering to the patient an antidepressant medication selected from the group consisting of: . . . .

2.  A method of administering an antidepressant medication to a patient in need thereof comprising:
    (1)  determining the patients genotype for following panel of genes: . . .
    (2)  assigning a metabolic phenotype to the patient based on the genotype of the cytochrome P450 genes in (1), wherein the metabolic phenotype is selected from poor (P), intermediate (I), and extensive (E), and said phenotype is assigned based upon the number of functional alleles for each cytochrome P450 gene as follows: P=either two partially functional alleles or two increased functional alleles, I=either one fully functional allele and a partially functional allele or one fully functional allele and an increased functional allele, and E=either one partially functional allele and one increased functional allele or two fully functional alleles; and
    (3)  administering to the patient an antidepressant medication selected from the group consisting of: . . . .

As at least two dozen alleles are to be tested for a given patient, and the list of potential medications to be administered in claim 2 is three pages long.  The '801 patent also includes claims directed to methods that "further compris[e] receiving, in a computer system, the patients genotype for the panel of genes, said computer system comprising a database, wherein said database comprises a plurality of antidepressant medication profiles," and "[a] non-transitory computer readable medium containing executable instructions that when executed cause a processor to perform operations comprising: (a) receiving a patient's genotype for a panel of genes . . . (b) assigning a metabolic phenotype to the patient based on the genotype of the cytochrome P450 genes in (1) . . .  and (c) outputting a list of medications suitable for administering to the patient . . . ."

Patent Profile: Nestec Receives Patent for Method of Predicting Risk of Celiac Disease

By Josh Bosman --

Earlier this month, the U.S. Patent and Trademark Office issued U.S. Patent No. 8,409,819, entitled "Methods to predict risk for celiac disease by detecting anti-flagellin antibody levels."  The '819 patent is assigned to Nestec S.A. of Vevey, Switzerland, a research and testing subsidiary of Nestlé.  (Interestingly, the application from which the '819 patent issued was originally assigned to Prometheus Laboratories Inc., which then assigned the application to Nestec.)

Celiac disease is a relatively common disease with an estimated prevalence of approximately 0.5%-1% resulting from both environmental factors (e.g., exposure to gluten), and genetic factors (e.g., HLA-DQ2/8 genotypes).  Currently, the only effective treatment for celiac disease is a life-long strict gluten free diet.  The inventors demonstrated that a subset of at risk patients had elevated anti-CBir1 antibodies and that this correlated with HLA-DQ2.5 and HLA-DQ8 genotypes.

The patent has two independent claims (claims 1 and 9) reciting two methods to aid in predicting whether a patient (who either has a relative with celiac disease or is EMA positive) is at risk of developing celiac disease.  Claim 1 recites:

1.  A method for aiding in the prediction of whether an individual having a relative with celiac disease (CD) is at risk of developing CD, the method comprising:
    (a) contacting a sample from the individual with a CBir1 flagellin antigen under conditions suitable to form a complex of the CBir1 flagellin antigen and an anti-CBir1 flagellin antibody, wherein the CBir1 flagellin antigen comprises the amino terminal conserved region (amino acid residues 1-147) of the sequence set forth in SEQ ID NO:1;
    (b) contacting the complex with a labeled antibody to form a labeled complex;
    (c) detecting the level of the labeled complex with a detection device, thereby determining a level of anti-CBir1 flagellin antibodies in the sample; and
    (d) associating an elevated level of anti-CBir1 flagellin antibodies in the sample relative to a control with a high risk of developing CD, thereby aiding in the prediction of whether an individual having a relative with CD is at risk of developing CD.

Both claimed methods use the CBir1 flagellin antigen, specifically the N-terminal residues 1-147, to determine whether or not a sample from an at-risk patient contains anti-CBir1 flagellin antibodies.  Flagellin is a component of bacterial flagella, the molecular apparatus responsible for a propeller like motion in bacteria.  As billions of bacteria make up the intestinal microbiota, the theory is that individuals at risk for celiac disease may have an aggressive immune response to resident bacterial proteins, in this case flagellin.  There are a number of highly specific and sensitive serological tests that can be used in diagnosing celiac disease; however the gold standard for diagnosis is histological examination of a biopsy acquired by endoscopic evaluation.  As some patients may wish to avoid an endoscopic procedure, or at least have additional confirmatory diagnostics before doing so, the methods claimed here may help clinicians in making a diagnosis.  The '819 patent also notes that the method may be useful for identifying groups of patients at risk of developing celiac disease before showing any symptoms, which could help in the development of preventative interventions or other alternatives to a strict gluten free diet (e.g., enzyme supplements).

Patent Profile: USPTO Issues Patent for Paromomycin-supplemented Turkey Feed for Prophylaxis of Histomoniasis and Improved Weight Gain

By Donald Zuhn --

Last month, the U.S. Patent and Trademark Office issued U.S. Patent No. 8,293,266, entitled "Paromomycin-supplemented feed stuff for turkey and use thereof for prophylaxis of histomoniasis, reduction of the horizontal spreading of histomoniasis, and for improved weight gain and feed conversion," to Huvepharma AD, a pharmaceutical company based in Sofia, Bulgaria.  The '266 patent is directed to a method of preventing the infection with or spread of histomoniasis or increasing weight gain in turkeys using a feed supplemented with paromomycin.

Histomoniasis (or blackhead disease) is a disease of poultry species, particularly chickens and turkeys, due to parasitic infection by a protozoan, Histomonas meleagridis.  The parasite specifically infects the cecum and liver of birds, with symptoms of the infection including depression, reduced appetite, poor growth, increased thirst, sulphur-yellow diarrhoea, listlessness, and dry, ruffled feathers.  Paromomycin (left), also known as monomycin and aminosidine, is an aminoglycoside antibiotic that was first isolated from Streptomyces krestomuceticus in the 1950s.  It is structurally related to neomycin, streptomycin, and kanamycin and has a broad spectrum of activity, including activity against protozoa, bacteria, and cestodes.  Surprisingly, the inventors found that the continuous application of paromomycin in feed in dosages below 1000 ppm, in the range 10-750 ppm, had a significant effect in:  (i) reducing the mortality of infected birds, (ii) significantly reducing the horizontal spread of the disease from infected to healthy birds, and (iii) improving the growth performance of the infected and non-infected animals.

The '226 patent issued on October 23, 2012 from U.S. Application No. 09/967,726, which was a U.S. national stage application of International Application No. PCT/BG2008/000003, which claims priority to Bulgaria Patent Application No. 109831.  Independent claims 1, 4, and 6 of the '226 patent recite:

1.  A method for preventing infection with or spread of histomoniasis in healthy turkey or in a flock of healthy turkey, the method comprising: formulating a feed stuff for turkey comprising feed supplemented with paromomycin in an amount sufficient to provide prophylaxis of histomoniasis; and feeding the feed stuff to the healthy turkey or flock of healthy turkey continuously from day 0 until slaughter or at least for more than one week; whereby infection or spread of histomoniasis in the healthy turkey or in the flock of healthy turkey is prevented.

4.  A method for reducing or preventing horizontal spread of histomoniasis in a flock of turkey, the method comprising: formulating a feed stuff for turkey comprising feed supplemented with paromomycin in an amount sufficient to provide prophylaxis of histomoniasis; and feeding the feed stuff to the flock of turkey continuously from day 0 until slaughter or at least for more than one week; whereby horizontal spread of histomoniasis is reduced or prevented in the flock of turkey.

6.  A method for increasing weight gain and improving feed efficiency in turkey or in a flock of turkey, the method comprising: formulating a feed stuff for turkey comprising feed supplemented with paromomycin in an amount sufficient to provide prophylaxis of histomoniasis; and feeding the feed stuff to the turkey or to the flock of turkey continuously from day 0 until slaughter or at least for more than one week; whereby weight gain is increased and feed efficiency is improved in the turkey or the flock of turkey.

Independent claims 8, 11, and 13 are identical to the above claims with the exception that the term "formulating" is replaced with "providing."

Patent Profile: Multicell Technologies Receives Stem Cell Patent

By Kwame Mensah --

Recently, MultiCell Technologies, Inc. of Woonsocket, RI, a clinical-stage biopharmaceutical company focusing on unmet medical needs for the treatment of neurological disorders, hepatic disease, and cancer, announced that it had been issued U.S. Patent No. 7,935,528, which is related to the isolation and use of human liver stem cells to treat liver disease.  MultiCell Technologies is the worldwide exclusive licensee of the '528 patent, which is assigned to Rhode Island Hospital.

The '528 patent describes methods to isolate and use human liver stem cells to treat degenerative liver diseases or inherited deficiencies of liver function.  MultiCell Technologies believes that one of the benefits of the claimed methods is that liver stem cells, which differentiate into functional mature hepatocytes, can be used to reconstitute a diseased liver.  This provides a useful alternative approach to whole organ transplants for certain liver diseases.

W. Gerald Newmin, Chairman and Chief Executive Officer of MultiCell Technologies, stated that the liver stem cells of the '528 patent would help the company "better understand liver stem cell biology, and the role these cells play in chronic liver disease and primary hepatocellular carcinoma."

Claim 1, which is the lone independent claim of the '528 patent, recites:

A primary liver stem cell, wherein said stem cell (a) is obtained from normal liver tissue, (b) is isolated from an isolated liver cell cluster comprising a hepatocyte and said stem cell, wherein said hepatocyte and said stem cell are joined by a desmosomal junction, (c) expresses OV6 [an oval cell marker], and (d) does not express OC2 [an oval cell marker], wherein said stem cell comprises a DNA encoding a heterologous protein. 

Patent Profile: Antisense Pharma Secures Patents for Convection Enhanced Delivery

By Kwame Mensah --

Earlier this month, Antisense Pharma, GmbH, a biopharmaceutical company located in Regensburg, Germany, announced the issuance of U.S. Patent No. 7,963,956, entitled "Portable equipment for administration of fluids into tissues and tumors by convection enhanced delivery technique," which is directed to Convection Enhanced Delivery (CED).  CED is being touted as an application system for long-term and outpatient administration of therapeutic substances into brain tissue.  The portable system was specially developed for the treatment of brain tumor patients using Antisense Pharma's drug Trabedersen.  Patents in Europe, Canada, Japan, and India, with additional patents being pursed worldwide, also cover CED.

Dr. Karl-Hermann Schlingensiepen, Chief Executive Of­ficer of Antisense Pharma, stated that CED provides a solution to "[t]he dif­ficulty of administering a therapeutic dose of a pharmacologically effective substance into the brain tissue due to the very small number of substances capable to pass the blood-brain barrier."  Dr. Schlingensiepen further stated that this difficulty "is one of the main reasons for the currently very few therapy options we can offer to brain tumor patients."  Antisense Pharma explains that CED uses a special infusion technology that provides a high and uniform concentration of active substances in the brain tissue -- even at a distance from the place of infusion.  The company explains further, that the substance is administered directly into the tumor or the surrounding brain tissue using a permanent, pressure-supported infusion using a special catheter/pump system.  It concludes that since CED builds up a pressure gradient, a clearly higher and more homogeneous penetration volume can be achieved compared to conventional diffusion.

Dr. Hubert Heinrichs, Chief Medical Of­ficer at Antisense Pharma, explains that with the development of the first portable, and now patented CED application system, "[t]he option of a CED-based treatment using a portable application system over weeks and months could well stimulate the development of urgently required neurotherapeutics."

The CED consists of several harmonized components.  After the catheter has been stereotactically placed in the tumor, the drug is administered via an infusion line using an external, programmable, portable pump.  The implantation of the catheter is a neurosurgical intervention, which is geared to the placement of a shunt for hydrocephalus patients where excessive brain liquid is diverted into the blood circulation.  The brain catheter is inserted through the skin to a port chamber, which is usually placed in the chest muscle.  The chamber is then connected to an external infusion line, which in turn is connected to a small, portable infusion pump that can easily be attached to the belt.  Dr. Schlingensiepen summarizes that:

Using this application system, we are able to administer highly effective drugs, by-passing the blood-brain barrier.  At the same time, we allow patients to continue living their normal lives during the therapy:  once the catheter system has been positioned, no extensive hospitalization is required.  The total 5-month treatment using Trabedersen provides patients with maximum mobility and quality of life.

Key claims encompass the CED apparatus itself and a method of use for the apparatus to treat a number of cancer tumors.

Patent Profile: BioNanomatrix Receives Nanofluidic Chip Patent

    By Nate Chongsiriwatana --

BioNanomatrix, Inc. recently announced the issuance of U.S. Patent No. 7,670,770 for nanochannel arrays that enable high-throughput macromolecular analysis.

Previously, single-molecule DNA analysis has been limited by the difficulty of linearizing (untangling) and manipulating intact native DNA.  To address these limitations, a Princeton University research team, including Dr. Han Cao, the founder and chief scientific officer of BioNanomatrix, used a nanofluidic chip to untangle and guide individual DNA molecules into an array of nanochannels.  According to Dr. Cao, the founder and chief scientific officer of BioNanomatrix, "this invention allows for true linear analysis of very long biomolecules such as native genomic DNA hundreds of thousands of base pairs in length without cloning or PCR amplification."  This technique, which is the basis for the company's NanoAnalyzer® system, can be used for multiplexed parallel processing applications, such as direct imaging analysis of structural variations in a person's genome and DNA mapping and sequencing.

At the crux of the invention are three critical dimensional qualities for nanochannel arrays that enable the simultaneous isolation and analysis of a multitude of elongated macromolecules.  Specifically, the '770 patent discloses that:  (1) the channels should be sufficiently narrow in order to elongate and isolate macromolecules; (2) the channels should be long enough to permit the instantaneous observation of the entire elongated macromolecule; and (3) a high number of channels should be provided in each array to permit the simultaneous observation of a large number of macromolecules.

The lone independent claim of the '770 patent reads:

1.  A method of isolating, imaging, and analyzing, in parallel, two or more individual nucleic acid biopolymers, comprising the steps of: providing a nanofluidic chip, comprising: a) nanochannel array, comprising: a surface having a plurality of parallel nanochannels running along the material of the surface, said nanochannels having a trench width of less than about 150 nanometers and a trench depth of less than 200 nanometers; at least one of the plurality of nanochannels being surmounted by sealing material to render such nanochannels at least substantially enclosed; at least two of the nanochannels capable of admitting a fluid; b) at least one sample reservoir in fluid communication with at least two of the nanochannels, said sample reservoir capable of releasing a fluid containing at least two nucleic acid biopolymer; providing the at least one sample reservoir with at least one fluid, said fluid comprising at least two nucleic acid biopolymers; transporting the at least two nucleic acid biopolymers into the at least two nanochannels to elongate said at least two nucleic acid biopolymers, the at least two nucleic acid biopolymers being individually confined within the at least two nanochannels such that the at least two nucleic acid biopolymer are transported through the at least two nanochannels in an unfolded fashion; imaging in parallel at least one signal transmitted from the at least two elongated and isolated nucleic acid biopolymers within the nanochannels; and correlating the signal to at least one property of the at least two nucleic acid biopolymers to thereby analyze the two or more individual nucleic acid biopolymers.

The specification also discloses methods of preparing nanochannel arrays and nanofluidic chips, methods of analyzing macromolecules, such as entire strands of genomic DNA, and systems for carrying out these methods.