Smash and grab

Published in Drug Discovery News

LA JOLLA, Calif.—Scripps Research Institute scientists have devised two highly specific methods to create new drugs, one that flings a single atom as a wrecking ball and another that can find therapy targets in tiny folds of microRNA.

 

A paper published in Nature in March describes research by Scripps chemistry professor Jin-Quan Yu that builds on his earlier groundbreaking development of using a weak chemical bond in molecule frameworks previously thought to be an obstacle, instead turning it into a powerful advantage when building drug compounds.

 

To attach function groups to chemical frameworks, a C-H bond must be broken—and it must be a specific, and possibly different, one for each potential intended attachment option.

 

“The best way to make a molecule is to replace a C-H bond directly,” Yu tells DDNews.

 

Some C-H bonds, though, don’t react, and are far away from attachment points of potential catalysts, rendering them difficult to break. With previous methods, “you cannot make certain types of molecules,” Yu says.

 

Yu’s insight, which he has been developing since 2002 at the University of Cambridge, was that he could install nitrile groups—weak connections that were dismissed in the past as hurting the structure of a framework—and use that weakness to facilitate the swinging of a catalyst across the molecular distance to a remote C-H bond, allowing it to be broken.

 

At that point, just as with other broken C-H bonds, functional groups that are building blocks for drugs can be attached, Yu said.

 

He originally published about the technique for what is called “meta” C-H activation inNature in 2012; the most recent paper has both simplified the process and allowed it to be applied more specifically to targeted C-H bonds.

 

“The key is to tune the shape of the template to create a subtle bias towards the targeted carbon hydrogen bond,” Yu said in Scripps’s announcement of the paper. “At the same time the template’s movement towards the target site has to be exploited effectively by a super-reactive catalyst.”

 

The chemical reagent involved will be available through Bristol-Myers Squibb’s catalog for order by laboratories, so that other researchers may use it in their own work, including targeting compounds common in drug discovery, such as tetrahydroquinoline, benzooxazines, anilines, benzylamines, 2-phenylpyrrolidines and 2-phenylpiperidines. “All these are commonly used in medicinal chemistry either as final drug compounds or intermediate compounds from which the final compounds are made,” Yu notes.

 

And in the future, he expects to further refine the technique so that the nitrile groups can be used catalytically, rather than needing to be installed and later removed.

 

The other approach, developed by Matthew Disney at the Scripps Florida campus, also inverts a standard method of searching for binding opportunities, this time in microRNA folds. Where previously researchers had to take RNA structures and do high-throughput screenings to find binding opportunities, Disney has built a database of potential types of bonds between RNAs and small-molecule function groups.

 

Then, by comparing given RNA sequences—not structures—to the database, Disney’s method can pinpoint possible opportunities. Only then does attention turn to the structures themselves, he tells DDNews: “Once we identify these interacting partners, could we find them … and drug it?”

 

Every disease has a relation to RNA, he said, because proteins play key roles in the process.

 

“If there’s some toxic protein … we can potentially target the RNA that makes that protein,” Disney says. (Alternately, if a disease causes too little of a protein to be produced, his technique can boost production.)

 

As a test case, and proof of concept, Disney and his team identified a druggable target—and its corresponding drug—in MiR-96 microRNA, which is believed to delay cell death by obstructing apoptosis, a natural cell-death process that begins when cells begin to grow in ways that are otherwise uncontrollable.

 

“People think that RNA can’t be drugged with a small molecule,” Disney says, but his approach proves that belief wrong. And it offers the prospect of very tightly targeting cells, in a way much narrower than the broad targeting approach taken today, where non-disease-related cells are also affected by therapies.

 

Next, Disney will go after diseases without current cures, such as Ebola, as well as orphan diseases that may need therapeutic-research attention.

 

While resistance to microRNA-targeting drugs is possible, Disney said his approach would help respond: “If resistance were to happen, and the RNA structure were to change,” then they could go back to the database and find binding matches for the new structure, he says.

Pharmacyclics: First drug gets rolling

Published in Drug Discovery News

SUNNYVALE, Calif.—Building quickly on the November 2013 approval of its first drug to market, Pharmacyclics has already achieved accelerated approval for that drug, Imbruvica (ibrutinib), in a second disease, with future plans for additional diseases.

 

The first approval came, under Breakthrough Therapy Designation, in mantle-cell lymphoma (MCL) for patients with one prior treatment; that was followed in February by approval for patients with one prior treatment in chronic lymphocytic leukemia (CLL), which the company’s chief medical officer, Jesse McGreivy, described as “a slow-growing blood cancer of the white blood cells” that is “the most common form of leukemia in the Western world.”

 

Company- and third-party-sponsored clinical trials continue in several other leukemias. In February, Imbruvica, which targets Bruton’s tyrosine kinase (BTK), a part of the B-cell receptor signal system, was added to the National Comprehensive Cancer Network’s Clinical Practice Guidelines in Oncology for relapsed/refractory MCL and relapsed/refractory CLL, as well as Waldenstrom’s macroglobulinemia (which currently has no drug treatment).

 

Reuters reported in February that RBC Capital Markets analyst Michael Yee predicted Imbruvica’s eventual annual global sales could reach $5 billion. McGreivy said there are 16,000 patients diagnosed with CLL every year in the U.S., and that more than 40,000 of the current 115,000 CLL patients have had a first therapy.

 

 

The potential market strength for the drug is further suggested by the fact that in December 2011 Janssen Pharmaceuticals, owned by Johnson & Johnson, agreed to pay 60 percent of drug-development costs and milestone payments, for a total of up to $975 million, in exchange for half of the drug’s profits.

 

Janssen is pursuing regulatory approval in more than 50 countries, Pharmacyclics CEO Robert Duggan said in a conference call announcing the CLL approval. Janssen is also helping significantly with sales, Paula Boultbee, Pharmacyclics’s executive vice president of sales and marketing, said in that call. She said the MCL approval kicked off a “strong launch” that was bolstered by several programs to ensure affordability of the drug—including a 30-day free supply for patients whose insurance companies take longer than five days to decide about coverage, and help limiting monthly out-of-pocket expenses for Imbruvica to $25 for qualifying patients. The average age of CLL patients is 72, according to company documents.

 

Imbruvica posted net product revenue of $13.6 million in the six weeks between its November 2013 approval and the close of the fourth quarter, according to Pharmacyclics’s most recent financial briefing.

 

The company’s net revenue for 2013 was $260.2 million, up 58 percent from $164.7 million in 2012. The remainder of the 2013 revenue was from the Janssen funding agreement, under which the recent CLL approval triggers a $60 million milestone payment.

 

A Leerink Partners analysis suggested that for the first quarter of 2014, Imbruvica sales could reach $50 million.

 

The rapid approvals for Imbruvica were supported by BioClinica, a Pennsylvania-based vendor of information-technology tools supporting clinical trials, including patient randomization, data collection and validation, and online analysis.

 

BioClinica works with the world’s biggest pharmaceutical manufacturers and tiny ones too, and touts its experience. “We as a vendor have worked on more clinical trials than most pharmaceutical companies,” Peter Benton, executive vice president and president of the eClinical Solutions division at BioClinica, tells DDNews.

 

Its systems allow efficient management of the enormous quantities of information generated by trials (“I’ve been in the industry long enough to remember tractor-trailers …  lined up waiting to deliver boxes and boxes of information on paper,” Benton said), and help vet and clean the data so it is ready for rapid processing by the FDA.

 

The company continues to expand by merger and acquisition to fill “white space between our current products,” Benton said. And in mid-March, BioClinica did it again, merging withCCBR-SYNARC. Both companies are owned primarily by the equity firms Water Street Healthcare Partners, and JLL Partners, and their combined services will support the entire drug-development spectrum, a merger-announcement statement said. The merged companies’ chairman will be Jeffrey McMullen, a longtime industry executive who in 2012 serves as chairman of the Association of Clinical Research Organizations.

Physicists are building an NSA-proof internet

Published on GlobalPost

BOSTON — It’s long been the Holy Grail of communications: technology that not only maximizes privacy, but also reveals when a message had been intercepted or copied.

The quest began in antiquity, with encryption and with the humble envelope — which not only kept out prying eyes but also showed if a message had been opened by someone other than its intended recipient.

More recently, Edward Snowden's revelations of spying by the National Security Agency have heightened concerns over electronic privacy, espionage and meddling.

Despite centuries of innovation, today’s methods for secure communication are basically the same — and in some ways are even more vulnerable, given how easy it is to copy, store, and search electronic data.

Scientists say a solution for truly private, tamper-free digital communication is underway, and should be commercially viable within a decade.

For theoretical physicists, the solution has already existed for several decades, but the technology needs refining before it’s available on a mass scale across the internet. Still, the pieces of this ultra-secure, high-speed communications web are beginning to take shape in labs around the world.

The system is based on quantum physics, and more specifically on the concept of “entanglement.”

Entanglement is a topic that even hardened scientists discuss with a degree of wonder. “It’s quite mysterious, in fact,” said Félix Bussières, a senior researcher in the Group of Applied Physics at the University of Geneva in Switzerland.

Physicists have long struggled to come up with metaphors and analogies to describe entanglement, which is so hard to actually wrap the mind around that even Albert Einstein gave up and settled for calling it “spooky.” It involves creating two photons (particles of light) that, while independent of each other and free to travel long distances apart, are still tightly interrelated, almost as if they are not two separate photons but one indivisible photon pair. As photons travel, they spin; each part of the entangled photon pair spins in the exact opposite direction from the other. If something happens that causes either of the pair to change its spin, the other instantaneously changes its spin to compensate.

Entangled photons act like a tripwire for any outside tampering — which is what makes a quantum internet so secure. In other terms, “quantum mechanics tell us that if you look at a quantum state you perturb it,” wrote Thomas Jennewein, an associate professor at theInstitute for Quantum Computing and in the physics and astronomy department of Ontario'sUniversity of Waterloo, in the institute’s 2013 annual report. (If you want to read more on the science, start by looking up the Heisenberg Uncertainty Principle and the Schrödinger’s catthought experiment.)

The good and bad of the quantum internet

So in the ideal case, wiretapping a quantum message system is impossible, Bussières said, because the wiretap will disturb the system, and the disturbance can be detected by the sender and recipient.

“The principle is perfectly secure,” Bussières said. “One can use in principle the quantum properties of light ... to ultimately cipher communication ... in a way that is ... provably unbreakable.”

This now works in the lab. It has even gone commercial: There is a small industry doing what is called quantum-key distribution — using quantum methods to generate encryption keys that are substantially more secure than more conventional ones. But the keys can only be shared across relatively small distances, no more than about 125 miles of optical fiber.

More from GlobalPost: NSA eyes encryption-breaking 'quantum' machine

The challenge is that the technology depends on photons (instead of electrons), and photons attenuate, or lose, their momentum over distance.

It also means that quantum connections are quite slow (about one megabit per second, Bussières said) compared to standard internet communications speeds. That’s why the technology is being used for keys instead of entire messages. And as such, while messages with quantum keys are more secure than others, they can still be monitored and copied for storage and later cracking by hackers or spies.

Quantum-key distribution could be poised for widespread commercialization right away, Bussières said, if technological advances threatened the security of conventional electronic encryption.

“If we want to go beyond these distances” with actual quantum connections, “other technologies are being intensely researched around the world,” he said. It would take several years to develop quantum-enabled devices that are small enough, cheap enough, and efficient enough to be mass-produced and widely used, “but considering the amount of research put in that direction, there is a great chance that it will become a reality,” Bussières said.

For nerds: solving the quantum quandary

To transform quantum communications from a lab project to a commercial application, three major approaches are in development: wavelength optimization, quantum repeaters, and satellite connections.

Scientists say the progress is encouraging, in part because much of the research involves adapting existing, conventional optical-communications gear to quantum uses, rather than inventing all-new equipment.

First, it’s not enough to simply connect photon-entanglement sources and detectors to opposite ends of optical-fiber cables. Because eventually photons attenuate — getting absorbed or scattering away from their detectors — even non-quantum-carrying fibers need help to keep the signal alive across long distances.

Steven Olmschenk, an associate professor of physics at Denison University in Ohio, is working to lengthen the distance entangled photons can travel in optical fiber. While previously he had also been working on quantum repeaters at the Joint Quantum Institute, he and others realized they were researching themselves into a bit of a corner.

Most of the photons used in quantum research so far, he said, are in ultraviolet wavelengths, which attenuate too quickly to be truly useful in fiber-optic transmissions. Internet and telecom companies already use infrared signals in fibers, because they attenuate more slowly.

Olmschenk’s research focuses on taking existing capabilities for UV quantum communications, and adapting them to infrared transmission and reception. It has only been a couple of years, though, and he told GlobalPost that while he is optimistic, he does not yet have any results to report.

If he is successful, he and others will also have to translate into UV the accomplishments of other researchers figuring out how to extend signals in other ways.

Bussières is working to improve quantum repeaters, which combine a photon detector, a quantum memory, and a photon source so that when a quantum signal needs to be transmitted, say 600 miles, that trip can be split by repeaters into shorter segments with less attenuation.

But for distances (or geographic features) too large to handle usefully with optical fiber, there is another option: sending quantum signals by satellite.

Jennewein, of the Institute for Quantum Computing, is on that task. He and his team have set their sights on sending entangled photons to satellites in low Earth orbit, likely somewhere around 300 to 360 miles above the ground. At present, open-air quantum transmissions have been achieved at around 100 miles, using transmitters and receivers that are very precisely aligned. (This gets harder when involving a satellite moving 15,000 miles per hour.)

Jennewein’s current work covers several aspects of the puzzle, including aiming photons accurately at distant receivers that are moving, determining how much attenuation will happen in the atmosphere as it thins at higher altitudes, and improving detection of the weak signals that will arrive.

One crucial challenge has not yet been undertaken: Because quantum sources need to be smaller and more energy-efficient before they are ready to fly in space, nobody has yet sent a quantum signal from a satellite back to Earth.

Other efforts, which would expand bandwidth over those extended distances, are also in the works. "Quantum dots," nanocrystals that conduct electricity, can simplify and even automate the process of emitting photons with particular entanglements on demand, which could help increase transmission rates, as would using light from LEDs instead of lasers. And repeaters capable of handling multiple quantum signals simultaneously would speed things up as well.

But the crucial part is building the connections that can span the world so that people can, it is hoped, finally communicate with complete privacy.

Three little maids from Maine: Opera stars come home for ‘Three Divas’ concert

Published in Out In Maine

When you’re a diva, you don’t have to meet the people you’ll be singing with before the day of the show. And you only need one group rehearsal — even if it’s for a big event like the 20th year of an opera company. Or so it might seem.

“It used to be a good thing” to be called a diva, laughs Suzanne Nance, who is one of three female opera singers slated to perform a show called “Maine’s Divas Come Home” at the University of Southern Maine’s Hannaford Hall on April 1 as part of PORTopera’s 20th anniversary celebration.

Nance, a soprano who is also a former Maine Public Broadcasting Network radio host now working at Chicago’s WFMT, will sing with another soprano, Ashley Emerson, and a mezzo-soprano, Kate Aldrich, a member of PORTopera’s advisory board and the first Maine native to fill a principal role in one of the company’s major productions — the title role in Carmen.

None of the three have ever sung together before, and Nance will be meeting Aldrich in person for the first time; she has met Emerson in the past. “We’re going to rehearse the day of” the show, with pianist Martin Perry, who himself is a well known musician in Maine and around the world. “We’ll basically run the whole show, while saving our voices,” Nance says. “We’ll just meet, put it together, and make a show of it.”

That show will be varied in terms of song choice and format.

“The open and close we’re going to go a la the Three Tenors,” Nance says, plus “three or four of the most beautiful duets in all of opera,” and several arias, from pivotal moments in significant shows that nevertheless “can come out and stand on their own.”

The songs are diverse, including works by classical masters Mozart and Verdi alongside modern standouts like Englebert Humperdinck.

Noting that the evening’s program will begin with an ensemble performance of “The Three Little Maids From School,” from Gilbert and Sullivan’s The Mikado, Ann Elderkind, PORTopera’s board president, says it’s appropriate the singers themselves “started as three little maids from Maine.”

Aldrich, originally from Damariscotta, “is so big in Europe,” Nance says. Based in Rome and New York City, Aldrich first sang the role of Carmen at PORTopera and has gone on to sing it across Europe, Elderkind adds.

Emerson, who grew up in Bangor, is a recent graduate of USM’s music program, focusing on voice performance. She was involved in PORTopera’s Emerging Artists program, and made her mainstage debut in the company’s 2003 production of Lucia di Lammermoor. Right out of college, she was accepted to a residency at the Metropolitan Opera in New York, where her career is “just taking off,” Nance says.

The singers are so busy, in fact, that it took about a year to coordinate everyone’s schedule, says Elderkind. And they had to pick the program in a Skype session, Nance says. When planning it, “we were all sort of giddy” about coming back to Maine, singing together, and seeing friends and family during the trip. “It’s great for us to come back and celebrate a place we love,” Nance says.

The event will also be celebrating the strength of the opera company, which has weathered a worldwide economic slump that forced bigger cities’ operas to close (including the New York Opera and the Baltimore Opera). Elderkind credits “the community of Maine coming forward” to support the company, especially in difficult times.

“Maine’s Divas Come Home” | Tuesday, April 1 @ 7:30 pm | Hannaford Hall, USM Abromson Center, Bedford St, Portland | $65 | porttix.com | portopera.org

The new normal: Conservatives try a different approach in fight against equality

Published in Out In Maine

In the last six months, as marriage equality and other LGBTQ rights have continued their inexorable expansion across the United States, it has become clear that instead of shaking the country to its core, or undermining America as we know it (as opponents have long alleged), protecting the rights of everyone in our society has benefited tens of thousands, perhaps even hundreds of thousands, of Americans in countless ways throughout their everyday lives.

What’s especially interesting is how quiet the ridiculous deep-seated opposition has actually become. The radical conservatives who for many years preached that recognizing the LGBTQ rights — same-sex marriage equality, employment non-discrimination, and more — would harm families, or kids, or communities, or the government, or the society, or something, have, it would appear, realized that marriage equality is not ending the world after all.

Writing in The Atlantic in early March, researcher Robert P. Jones reported that his studies showed nearly half of all Southerners now support same-sex marriage. Despite all the legal action and court decisions, he wrote, “these changes cannot be explained away as merely another example of federal judicial activism circumventing the will of the people in southern states. Rather, we are witnessing dramatic cultural transformations, which include changing minds even among culturally and religiously conservative Americans in the South.”

Even conservative pundits seem to be noticing this progress. Fox News commentator Howard Kurtz wrote in early March about a Washington Post/ABC poll with showing 59 percent of Americans support same-sex marriage, and only 34 percent opposing. That’s almost an exact reversal of the numbers from the same poll in 2004, which Kurtz calls “a headspinning shift.”

He observes that “even GOP politicians who are against [same-sex] marriages are muting their opposition,” attributing that decision to the fact that “three-quarters of Americans under 30 back same-sex marriage (as opposed to less than half of senior citizens).”

With same-sex marriage recognized at the federal level and legal in 17 states — and with marriage inequality under siege in most of the 33 states where it is not yet legal — conservatives are in retreat. (See sidebar, “Scorecard.”)

Surrender?
In fact, conservative New York Times columnist Russ Douthat’s March 2 column was entitled “The Terms of Our Surrender.” Spoiler: It’s not really a surrender. Rather, it highlights a change in the scale and scope of the fight to one much larger and broader than the terms of civil marriage.

No longer inveighing against what he and others called the “redefinition” of marriage to include all consenting adults, Douthat asked his readers to redefine the idea of “religious freedom” to mean protecting, effectively, anything they feel like doing at any time, for any reason.

A great many people around the country are now objecting to laws barring their businesses, places of public accommodation, and workplaces from discriminating against same-sex couples, on the grounds that, somehow, discrimination is part of their religious philosophy and therefore outside the realm of government control.

Douthat came to a spirited defense of that prodiscrimination perspective — even terming it a “subculture,” simultaneously admitting its small and dwindling numbers and suggesting it should be preserved. He lamented the prospect that wedding photographers and adoption agencies might “be treated like the proprietor of a segregated lunch counter,” and face penalties for continued discrimination.

Continuing his sad hypothetical, Douthat posits that “eventually, religious schools and colleges would receive the same treatment as racist holdouts like Bob Jones University, losing access to public funds and seeing their tax-exempt status revoked.”

Carving out religious-freedom protections is a common method of ensuring religious institutions are not compelled by the government to change their teachings; Maine’s law, like those in many other states, was strategically written to allow churches and ordained ministers to decide for themselves whether they consecrate or celebrate same-sex marriages.

But Douthat wants much more. For him, individuals should be able to decide for themselves whether they treat other humans with dignity and respect — or whether their religious beliefs allow them to discriminate.
In fact, in March, the US Supreme Court is expected to rule on whether corporations can hold religious beliefs and, if so, whether those beliefs can exempt corporations from a great many state and federal laws.

Douthat wraps up with a weird pronouncement that seems to blame the people he views as victims: “Christians had plenty of opportunities — thousands of years’ worth — to treat gay people with real charity, and far too often chose intolerance. (And still do, in many instances and places.) So being marginalized, being sued, losing tax-exempt status — this will be uncomfortable, but we should keep perspective and remember our sins, and nobody should call it persecution.”

And his final line could be called fatalistic if it weren’t such a call to arms: “all that’s left is the timing of the final victory — and for the defeated to find out what settlement the victors will impose.”

Scorecard: Where discrimination is under attack
What Russ Douthat and other conservatives are seeing, and recognizing the inevitability of, is the march to the courthouse of LGBTQ Americans across the country. Sadly, most of them are not yet heading there to get married — rather, they’re suing to force states to allow and recognize their marriages.

According to NBC News reporter Pete Williams, “cases are now pending in all but eight of the 33 states that forbid gay couples to marry.” Last June’s US Supreme Court decision striking down Section 3 of the Clinton-era Defense Of Marriage Act has opened the floodgates.

Williams’s tally says 17 states permit same-sex marriage, 29 ban it under an amendment to the state constitution, and the remaining four ban it in state statute.

With cases in almost every state, and appeals in process in several circuits, “it seems a near certainty that the issue will be back at the US Supreme Court soon, either by the next term that begins in October or the year after,” Williams wrote.

Here, compiled primarily from pro-marriage groups Marriage Equality USA and Freedom to Marry, is a rundown of where all 50 states stand:

ALABAMA | A case was filed in December 2013 to overturn ban, and to force recognition of marriages performed in other states.

ALASKA | The state Supreme Court is considering a denial of survivor benefits as a result of constitutional and legal bans.

ARIZONA | Two cases, one in state court and another in federal court, are pending against the 2004 constitutional band; in January, the state asked for dismissal of the federal case.

ARKANSAS | In January, a class-action suit was filed seeking to overturn the state’s bans, a 1996 law and a 2004 constitutional amendment. That builds on a 2010 case seeking to preserve health benefits for state workers. They are getting benefits now, under current rulings, but the case just received class-action status covering all Arizona state workers with same-sex partners.

CALIFORNIA | Legal

COLORADO | Four cases, all in state court, seek to overturn the 2004 constitutional amendment ban, which also created non-marriage civil unions.

CONNECTICUT | Legal

DELAWARE | Legal

FLORIDA | State and federal suits are pending, trying to overturn the 2008 constitutional amendment ban.

GEORGIA | no challenges

HAWAII| Legal

IDAHO | A federal case seeks to reverse the 2006 constitutional amendment ban, which is being defended by the state attorney general; in may, a judge will consider whether to skip the trial and just issue a ruling.

ILLINOIS | Legal

INDIANA | in early march, four couples sued in federal court seeking marriage rights and to overturn the state’s statutory ban.

IOWA | Legal

KANSAS | A December 2013 lawsuit asks permission for a same-sex couple married elsewhere (Kansas has a constitutional ban) to file joint income-tax returns.

KENTUCKY | On February 12, a federal judge ruled the state’s ban unconstitutional; if an appeals court does not issue a delay, same-sex couples will have full legal rights starting March 20. The state attorney general says he will not appeal the case, but the governor says he will. Also, marriages performed elsewhere are recognized.

LOUISIANA | Three cases seek to overturn statutory and constitutional bans; the state is defending those bans.

MAINE | Legal

MARYLAND | Legal

MASSACHUSETTS | Legal

MICHIGAN | Federal judge will rule in late March on challenge to 2004 voter-approved state ban.

MINNESOTA | Legal

MISSISSIPPI | A case seeks to force the state to recognize an out-of-state same-sex marriage for the purpose of granting a divorce; there is no active challenge yet to the state’s constitutional ban, but preparations are under way.

MISSOURI | There is not yet a case directly challenging the state’s constitutional ban, but two cases do seek to require recognition of out-of-state same-sex marriages.

MONTANA | A case in state court now seeks “all of the benefits of marriage, other than marriage itself,” according to Marriage Equality USA.

NEBRASKA | no challenges

NEVADA | In 2012 a federal judge rejected a challenge to its 2002 constitutional ban; an appeal will be heard by the 9th circuit soon, but the state’s attorney general and governor are not supporting the ban.

NEW HAMPSHIRE | Legal

NEW JERSEY | Legal

NEW MEXICO | Legal

NEW YORK | Legal

NORTH CAROLINA | Republican lawmakers are defending the statutory and constitutional bans; a county register of deeds has also said he will ask the state attorney general to decide whether marriage licenses can be issued to same-sex couples.

NORTH DAKOTA | no challenges

OHIO | In December 2013, a federal judge overturned the state’s 2004 constitutional ban; the attorney general has appealed the ruling to the 6th circuit.

OKLAHOMA | In January, a federal judge overturned the state’s constitutional ban; the state’s appeal will be heard in April in the 10th circuit.

OREGON | A federal suit challenges the state’s constitutional ban; arguments will be heard in april, but the state attorney general has said she will not defend it.

PENNSYLVANIA | Several state and federal cases oppose the statutory ban; the attorney general has said she will not defend it.

RHODE ISLAND | Legal

SOUTH CAROLINA | A federal suit was filed in August 2013 seeking to overturn the state’s constitutional and statutory bans.

SOUTH DAKOTA | no challenges

TENNESSEE | A federal suit asks a judge to overturn the statutory and constitutional bans.

TEXAS | Numerous state and federal cases challenge the constitutional ban and other statutory restrictions on equality, including an appeal before the 5th circuit of a February ruling striking down the bans.

UTAH | In December 2013, a federal judge struck down the state’s constitutional amendment; its appeal will be heard in April in the 10th circuit. another federal case seeks to protect about 1300 same-sex couples who were legally married in Utah after the December decision and before the US Supreme Court’s January stay of the ruling.

VERMONT | Legal

VIRGINIA | In February, a federal judge overturned the 2006 constitutional ban; the decision is stayed pending an appeal decision by the 4th circuit. the state attorney general has not defended the ban, and instead intends to join the plaintiffs seeking to have it struck down.

WASHINGTON | Legal

WEST VIRGINIA | A federal suit, which is opposed by the state attorney general, seeks to overturn the statutory ban.

WISCONSIN | A case before the state supreme court challenges the 2006 constitutional ban and a 2009 domestic-partnership law; a decision is expected this summer. a federal suit also challenges those bans, as well as a Wisconsin-only law banning same-sex couples from marrying elsewhere under penalty of fine and imprisonment.

WYOMING | In March a state lawsuit was filed seeking to strike down the statutory ban.

WASHINGTON DC | Legal

Equality Overseas
Same-sex marriage rights are an equally hot topic in other countries. The most attention has been given to Russian president Vladimir Putin, who continues to enforce his country’s sweepingly vague ban on “gay propaganda,” while his people overwhelmingly object to same-sex marriages.

In Africa, serious legal barriers are still being erected. (Only South Africa has legalized same-sex marriage.)

Uganda, the most aggressively anti-gay country on that continent, recently enacted a law that could sentence homosexuals to life imprisonment. Faced with Western objection to that law, president Yoweri Museveni complained about “social imperialism,” saying foreigners were trying to “impose social values” on his people.

The Uganda-based Civil Society Coalition on Human Rights and Constitutional Law recently released 20 guidelines for national and international allies on “how to offer support now that the anti-homosexuality law has been assented to.” among their suggestions:

-“call on multinational companies that have businesses in Uganda [such as Heneiken, British Airways, and Barclays Bank] to go public about their concerns [about] the act and their future economic engagements in Uganda.”

-“expand investment in funding for service delivery and advocacy in defiance of the law, targeting LGBT populations, to attempt to mitigate the harmful impact this law will have on access to services, and on human rights.”

-“call for your government to issue travel advisories on Uganda...alerting their own LGBT citizens to the risk of traveling in Uganda.”

-“draw international public attention to issues such as corruption, human trafficking...land-grabbing, as well as the suppression of media freedom and civil society space... so that attention shifts to where it properly belongs: in the best interests of the country’s population as a whole.”

Asia is another place with little-to-no recognition: the best status for same-sex marriage is in Israel, where marriages themselves are not allowed, but where the government recognizes them if legally performed elsewhere.

Nepal, Taiwan, and Vietnam are among the countries that do have active discussions under way. and the Dalai Lama recently became the first Buddhist leader to endorse same-sex marriage.

In the Pacific, Australia bans same-sex marriage; New Zealand allows it. Most of the island nations don’t recognize same-sex marriages; several also ban all homosexual activity.

In the Americas, Canada allows same-sex marriage; Mexico and several other Central American countries only recognize same-sex marriages performed elsewhere. South America is fairly split, though powerhouses Brazil and Argentina (as well as smaller nation Uruguay) have same-sex marriage. Colombia and Ecuador have some legal rights for same-sex couples.

Most Western European countries (though not Italy) recognize same-sex marriages or offer some sort of government-registered partnership; Eastern European countries are uniform in not recognizing same-sex marriages, and several nations in that area have specific opposite-gender requirements for marriage.